Pediatric Anaerobic Infections: Diagnosis and Management (Infectious Disease and Therapy)

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Pediatric Anaerobic Infections: Diagnosis and Management (Infectious Disease and Therapy)

To my wife, Joyce, and my children, Dafna, Dan, Tamar, Yoni, and Sara The last edition of the book was published as Ped

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To my wife, Joyce, and my children, Dafna, Dan, Tamar, Yoni, and Sara

The last edition of the book was published as Pediatric Anaerobic Infection: Diagnosis and Management, Second Edition, © The C. V. Mosby Company (St. Louis, 1989).

ISBN: 0-8247-0615-3 This book is printed on acid-free paper. Headquarters Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016 tel: 212-696-9000; fax: 212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 812, CH-4001 Basel, Switzerland tel: 41-61-261-8482; fax: 41-61-261-8896 World Wide Web http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright © 2002 by Marcel Dekker, Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. Current printing (last digit): 10

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PRINTED IN THE UNITED STATES OF AMERICA

Preface

Since the publication of the second edition of the book in 1989, much has changed in our understanding and knowledge of the role of anaerobic bacteria in infections in children. More clinical studies have been performed, describing the activity of these bacteria in a variety of infections, which include splenic and liver abscesses, infections after trauma, and head and neck and abdominal infections. With increased awareness, patient care has improved in those infected by these organisms. With the passage of time, there has been an increase in the resistance of anaerobic bacteria to many of the antimicrobials used against them. During this period, newer antimicrobial agents effective against these organisms have been introduced. Methods for their identification have been improved and simplified, as their taxonomy has changed. The third edition of the book updates our knowledge of the role of anaerobic bacteria in pediatric infections. All the chapters have been revised to provide current information about diagnosis and therapy, resistance to antimicrobials, the newer agents, indications and contraindications for surgery, and the therapy of complications. Newer diagnostic tests have been included, the nomenclature of the organisms has been updated, and newer and updated references have been provided. Each chapter presents the information in the most user-friendly way, and emphasis has been given to treatment of various infections for ready use by pediatricians and family practitioners, as well as teaching institutions. I believe that practicing physicians will continue to find this reference useful in delivering care for their patients. Itzhak Brook

iii

Acknowledgments

I am most grateful to those who have made this book possible. I would like to express my deepest gratitude to my parents, Haya and Baruch, who worked so hard to ensure that I would have a proper education. They have always encouraged the development of my scientific curiosity and capabilities. I would also like to thank my children and especially my wife, Joyce, for their patience, assistance, and understanding. I am indebted to many of my teachers in the Hareali Haivri High School of Haifa, Israel, for their devotion and enthusiastic teaching, which were instrumental in promoting my scientific, professional, and ethical development. I am especially grateful to my biology teacher, Z. Zilberstein, for his enthusiastic recognition of nature’s role in human life, and to my physics teacher, L. Green, for teaching me an analytical and scientific approach to my studies. I am grateful to many of my teachers in the Hebrew University Hadassah School of Medicine in Jerusalem and especially to the late Professor H. Berenkoff, who introduced me to the wonders of microbiology; to Dr. T. Sacks, who taught me clinical microbiology; and to Dr. S. Levine from Kaplan Hospital, Rehovot, Israel, who taught me general pediatrics. I owe special gratitude to my teacher and mentor at University of California, Los Angeles, Dr. S. M. Finegold, for sharing his knowledge of anaerobic microbiology and clinical infectious diseases. Dr. Finegold has served over the years as a constant source of support and encouragement. Other teachers who provided invaluable help are Drs. W. J. Martin and V. L. Sutter from University of California, Los Angeles, and Drs. C. V. Sumaya, G. D. Overturf, and P. Wherle, who taught me about pediatric infectious diseases. I am also grateful to my friends and collaborators who assisted in many of the clinical and laboratory studies: K. S. Bricknel for his excellent gas liquid chromatography work, and L. Calhoun and P. Yocum for their dedication and laboratory support. Finally, I would like to thank the many medical students, house officers, infectious diseases fellows, and faculty and staff members at the Medical Centers of the University of California, Los Angeles; University of California, Irvine; George Washington University and Georgetown University, Washington, D.C.; and the Naval Hospital in Bethesda, Maryland, for their collaboration in clinical studies. v

Contents

Preface Acknowledgments

iii v

Part I Introduction to Anaerobes 1 2 3 4 5

Anaerobes as Pathogens in Childhood The Indigenous Microbial Flora in Children Collection, Transportation, and Processing of Specimens for Culture Clinical Clues to the Diagnosis of Anaerobic Infections Virulence of Anaerobic Bacteria and the Role of the Capsule

1 25 41 55 63

Part II Neonatal Infections 6 7 8 9 10 11 12 13 14 15

Introduction to Neonatal Infections Colonization of Anaerobic Flora in Newborns Conjunctivitis and Dacryocystitis Pneumonia Ascending Cholangitis Following Portoenterostomy Cutaneous Infections Bacteremia and Septicemia Necrotizing Enterocolitis Infant Botulism Scalp Infection Following Intrauterine Fetal Monitoring

75 79 87 91 95 99 109 119 129 139

Part III Anaerobic Infections of the Specific Organ Sites 16 17

Infections of the Central Nervous System Eye Infections

145 169 vii

viii

18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

Contents

Odontogenic Infections Ear, Nose, and Throat Infections Infections of the Head and Neck Chest Infections Intra-Abdominal Infections Urinary Tract and Genitourinary Suppurative Infections Female Genital Tract Infections Cutaneous and Soft Tissue Abscesses and Cysts Soft-Tissue and Muscular Infections Burn Infections Decubitus Ulcers Surgical Wound Infections Human and Animal Bite Wounds Infected Solid Tumors Infections of Bones and Joints Clostridial Diarrhea and Pseudomembranous Enterocolitis Endocarditis Pericarditis

187 205 279 311 339 365 379 393 415 431 439 445 455 465 471 489 499 505

Part IV Other Types of Anaerobic Infections 36 37 38

Anaerobic Bacteremia Botulism Tetanus

509 523 531

Part V Principles of Management 39 40

Treatment of Anaerobic Infections Beta-Lactamase–Producing Bacteria in Mixed Infections in Children

Index

545 569 595

1 Anaerobes as Pathogens in Childhood

Anaerobic bacteria differ in their pathogenicity. Not all of them are believed to be clinically significant, while others are known to be highly pathogenic. Table 1.1 lists the major anaerobes that are most frequently encountered clinically. The species of anaerobes most often isolated from clinical infections are, in decreasing frequency, gramnegative rods (Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Bilophila, and Sutterella), gram-positive cocci (primarily Peptostreptococcus), gram-positive spore-forming (Clostridium) and non-spore-forming bacilli (Actinomyces, Propionibacterium, Eubacterium, Lactobacillus, and Bifidobacterium), and gram-negative cocci (mainly Veillonella).1 About 95% of the anaerobes isolated from clinical infections are members of these genera (Table 1.2). The remaining isolates belong to species not yet described, but these can usually be assigned to the appropriate genus on the basis of morphologic characteristics and fermentation products. The frequency of recovery of the different anaerobic strains differs in various infectious sites. We have summarized our experience in recovering anaerobic bacteria over a period of 12 years from both adults and children.2 Anaerobic gram-negative bacilli (Bacteroides, Prevotella, and Porphyromonas) accounted for 43% of anaerobic isolates (Table 1.2). They were predominant in genitourinary infections (56% of all anaerobic isolates), abdominal infections (55%), abscesses (51%), obstetric and gynecologic infections (49%), infected cysts (44%), wounds (43%), and tumors (42%). They were less often recovered in infections of the central nervous system (7%), eye (12%), joint (13%), and lymph glands (15%). Anaerobic gram-positive cocci accounted for 26% of all isolates. The infected sites where they predominated were ears (53%), cysts (40%), bones (39%), and obstetric and gynecologic (35%). They were uncommonly found in the eye (6%), bile (12%), abdomen and lymph gland (13% each), and central nervous system (17%). Clostridium spp. were 7% of all isolates. They predominated in infection of the bile (36%), abdomen and wound (13% each), joint (12%), and blood (11%). They were less commonly found in tumors and sinuses (1% each) or the genitourinary tract, ears, and cysts (2% each). 1

2

Chapter 1

Table 1.1 Anaerobic Bacteria Most Frequently Encountered in Clinical Specimens from Children Organism

Infection Site

Gram-Positive cocci Peptostreptococcus sp. Respiratory tract, intra-abdominal and subcutaneous infections Microaerophilic streptococcia Sinusitis, brain abscesses Gram-positive bacilli Non-spore-forming Actinomyces sp. Intracranial abscesses, chronic mastoiditis, aspiration pneumonia, head and neck infections Propionibacterium acnes Shunt infections (cardiac, intracranial) Bifidobacterium sp. Chronic otitis media, cervical lymphadenitis Spore-forming Clostridium sp. C. perfringens Wounds and abscesses, sepsis C. septicum Sepsis C. difficile Diarrheal disease, colitis C. botulinum Infantile botulism C. tetani Tetanus Gram-negative bacilli B. fragilis group (B. fragilis, Intraabdominal and female genital tract infections, sepsis, B. thetaiotamicron) neonatal infection Pigmented Prevotella and Orofacial infections, aspiration pneumonia, periodontitis Porphyromonas sp. Prevotella oralis Orofacial infections Prevotella oris-buccae Orofacial infections, intraabdominal infections Prevotella bivia, Female genital tract infections Prevotella disiens Fusobacterium sp. F. nucleatum Orofacial and respiratory tract infections, brain abscesses, bacteremia F. necrophorum Aspiration pneumonia, bacteremia a

Not obligate anaerobes.

Fusobacterium sp. accounted for 5% of all isolates. They were often found in infections of the chest (11%), abdomen (8%), and sinuses (7%). They were infrequently recovered in tumors, cysts, the central nervous system, and bile (1% each); ears and wounds (2% each); and obstetric and gynecologic infections (3%). This chapter provides a discussion of each of the important anaerobic species recovered from children and the role of these organisms in infectious processes. CLASSIFICATION OF ANAEROBES Anaerobes do not multiply in oxygen. However, they possess different susceptibilities to oxygen. Most normal-flora anaerobes are extremely oxygen-sensitive, while those that

Anaerobes as Pathogens in Childhood

3

cause infections are more aerotolerant. The negative oxidation-reduction potential (Eh) of the environment is a critical factor. However, aerotolerance is achieved by several anaerobes through the production of superoxide dismutase on exposure to oxygen. The recent use of DNA technology and chemotaxonomic analysis has clarified many taxonomic relationships among anaerobes. These affected mostly anaerobic grampositive cocci and Bacteroidaceae. Anaerobes do not grow on solid media in room air (10% CO2, 18% O2); facultative anaerobes grow both in the presence and absence of air; and microaerophilic bacteria grow poorly or not at all aerobically but grow better under 10% CO2 or anaerobically. Anaerobes are divided into “strict anaerobes,” which are unable to grow in the presence of >0.5% O2 and “moderate anaerobes,” which are capable of growing at between 2% and 8% O2. GRAM-POSITIVE SPORE-FORMING BACILLI Anaerobic spore-forming bacilli belong to the genus Clostridium. Morphologically, the clostridia are highly pleomorphic, ranging from short, thick bacilli to long, filamentous forms; they are either ramrod-straight or slightly curved. The clostridia found most frequently in clinical infections are Clostridium perfringens, Clostridium septicum, Clostridium butyricum, Clostridium ramosum, and Clostridium innocuum. C. perfringens is an inhabitant of soil and of intestinal contents of humans and animals and is the most frequently encountered histotoxic clostridial species. This microorganism, which elaborates a number of necrotizing extracellular toxins, is easily isolated and identified in the clinical laboratory. C. perfringens seldom produces spores in vivo. It can be characterized in direct smears of a purulent exudate by the presence of stout gramvariable rods of varying length, frequently surrounded by a capsule. C. perfringens can cause a devastating illness with high mortality. Clostridial bacteremia is associated with extensive tissue necrosis, hemolytic anemia, and renal failure. The incidence of clostridial endometritis, a common event following septic abortions, has decreased as medically supervised abortions have increased.1 C. perfringens accounted for 48% of all clostridial isolates in our hospitals and was primarily isolated from wounds (26% of C. perfringens), blood (16%), abdomen (14%), and obstetric and gynecologic infections (13%). C. septicum, long known as an animal pathogen, has been found in humans within the last decade, often associated with malignancy. The intestinal tract is thought to be the source of the organism, and most of the isolates are recovered from blood (Table 1.3). Although Clostridium botulinum usually is associated with food poisoning, wound infections caused by this organism are being recognized with increasing frequency. Proteolytic strains of types A and B have been reported from wound infections. Disease caused by C. botulinum usually is an intoxication produced by ingestion of contaminated food (uncooked meat, poorly processed fish, improperly canned vegetables) containing a highly potent neurotoxin. Such food may not necessarily seem spoiled, nor may gas production be evident. The polypeptide neurotoxin is relatively heat-labile, and food containing this toxin may be rendered innocuous by exposure to 100°C for 10 min. Infection of a wound with C. botulinum occurs rarely and can produce botulism. C. botulinum has been associated with newborns presenting with hypotonia, respiratory arrest, areflexia, ptosis, and poorly responding pupils. Botulism in growing infants

4

Chapter 1

Table 1.2 Percentage of Recovery of Anaerobes in Each Infection Site (Walter Reed Army Medical and Naval Medical Centers, 1973–1985)

Specimen Source Abdomen Abscess Bile Bites Blood Bone Central nervous system Chest Cysts Ear Eye Genitourinary Grafts Joints Lymph glands Obstetric/gynecologic Sinuses Tumors Wounds Miscellaneous Total

Total number of Specimens

Total number of Anaerobic Isolates

Number of Anaerobic Isolates/ Specimen

Gram-negative bacillia sp.

359 820 66 9 587 37 220 191 206 25 55 30 13 63 70 871 102 61 622 51 4458

550 1416 75 12 634 69 225 283 348 47 66 52 15 69 76 1328 159 79 987 67 6557

1.53 1.73 1.14 1.33 1.08 1.86 1.02 1.48 1.69 1.88 1.20 1.73 1.15 1.10 1.09 1.52 1.56 1.30 1.59 1.31 1.47

299(55)b 725(51) 29(39) 5(42) 222(35) 24(35) 16 (7) 101(37) 153(44) 12(26) 8(12) 29(56) 4(27) 9(13) 11(15) 654(49) 53(33) 33(42) 425(43) 23(34) 2835(43)

Fusobacterium sp. 43 (8) 97 (7) 1 (1) 1 (8) 24 (4) 4 (6) 2 (1) 31(11) 5 (1) 1 (2) 3 (5) 2 (4)

3 (4) 42 (3) 11 (7) 1 (1) 20 (2) 3 (4) 294 (5)

a

Including Bacteroids, Prevotella, and Porphyromonas spp. In parentheses: percentage of all anaerobic bacteria isolated from source indicated. Source: Ref. 2.

b

is caused by toxin from the germination of ingested spores and C. botulinum in the bowel lumen. C. butyricum was isolated from blood cultures obtained from 12 newborns with necrotizing enterocolitis; however, the exact clinical association of this organism with the disease has not been established.3 C. butyricum can be recovered from infection of the abdomen, abscesses, bile, wounds, and blood. Clostridium difficile has been incriminated as the causative agent of antibiotic-associated and spontaneous diarrhea and colitis.4 This bacterium was also recovered from infected sites in children, such as the peritoneal cavity, blood, and lungs5 and from wounds and central nervous system infections. Clostridium tetani rarely is isolated from human feces. Infections caused by this bacillus are a result of contamination of wounds with soil containing C. tetani spores. The spores will germinate in devitalized tissue and produce the neurotoxin that is responsible for the clinical findings. C. tetani has been recovered from patients presenting with otogenous tetanus.6 Clostridia are commonly isolated from various infections in children. They are especially prevalent in abscesses (mostly abdominal, in the rectal area, and oropharyn-

Anaerobes as Pathogens in Childhood

5

Clostridium Lactobacillus Eubacterium Propionibacterium Bifidobacterium sp. sp. sp. sp. sp. 71(13) 71 (5) 27(36)

4(1) 7(0.5)

31(6) 44(3)

70(11) 2 (3) 4 (2) 18(6) 6 (2) 1 (2) 11(17) 1 (2) 1 (7) 8(12)

1(0.2)

13(2) 1(1)

1(0.4) 4(1)

9(3) 6(2)

1(2)

3(6)

50(4) 2 (1) 1 (1) 124(13) 3 (4) 471(7)

1(1) 15(1)

6(1) 40(1)

28(2) 2(1) 1(1) 18(2) 2(3) 158(2)

23 (4) 54 (4) 9(12) 2(17) 229(36) 9(13) 163(72) 51(18) 24(7) 7(15) 36(55) 3(6) 5(33) 39(57) 48(63) 28(2) 36(23) 22(28) 66(7) 20(30) 874(13)

5(0.5)

Actinomyces Veillonella sp. sp. 2(0.2)

1(0.2)

8(1) 28(2)

7(1) 2(3) 1(0.5)

4(1) 1(0.3)

1(1) 12(1) 1(1) 1(0.1) 1(1) 27(0.4)

9(3) 10(3) 1(2) 4(6) 2(4)

1(1) 1(1)

5(0.1)

2(3) 28(26) 7(4) 1(1) 14(1) 2(3) 125(2)

geal), peritonitis, and otolaryngological infections, as has been shown in adults.1 The distribution of clostridia in these infections is explained by their prevalence in the normal gastrointestinal and cervical flora, from which they may originate.7 Clostridial strains (C. perfringens, C. butyricum, and C. difficile) have been recovered from blood and peritoneal cultures of necrotizing enterocolitis and from infants with sudden death syndrome.8–10 Strains of Clostridium were recovered from children with bacteremia of gastrointestinal origin11 and with sickle cell disease.12 Clostridial strains have been recovered from specimens obtained from children with acute13 and chronic otitis media,14 chronic sinusitis15 and mastoiditis,16 peritonsillar abscesses,17 peritonitis,18 and neonatal conjunctivitis.19 We have summarized our experience over a period of 17 years (1973 to 1990)20 in the isolation of Clostridium species from 1543 specimens sent to anaerobic microbiology laboratories. The survey revealed 113 isolates from 107 specimens (7.0% of all specimens) from 96 children (Table 1.3.) The isolates comprised 43 (38%) unidentified Clostridium spp., 37 (33%) C. perfringens, 13 (12%) C. ramosum, 5 (4%) C. innocuum, 6 (5%) C. botulinum, 3 (3%) C. difficile, 2 (2%) C. butyricum, and one isolate each of C.

6

Chapter 1

Table 1.3 Clostridium spp. Isolated from 96 Children Number of specimens

Type of Infection Neonatal Infection Bacteraemia Cholangitis Conjunctivitis Omphalitis Scalp Older Children Abscesses Bacteraemia Burn wound Decubitus ulcer Ear: Acute otitis Chronic otitis Mastoiditis Lungs: Empyema Pneumonia Osteomyelitis Peritonitis Sinusitis Total

Total

With Clostridium sp.a

121 8 35 23 23

1(1) 3(1) 2(1) 2 1

384 42 180 58

38(1) 9(7) 1 2

28 94 24

3(1) 7(1) 3

72 74 26 116 45 1543

Number of isolates C. bifermentans

1 1 4(1) 26 3 107(14)

C. botulinum

C. butyricum

C. clostridiiforme

1

2

1

4

2

6

2

1

Source: Ref. 20. a = number of clostridium recovered as the only isolate.

bifermentans, C. clostridiiforme, C. limosum and C. paraputrificum. Most clostridial isolates were from abscesses (38), peritonitis (26), bacteraemia (10), and chronic otitis media (7). Predisposing or underlying conditions were present in 31 (32%) cases. These were immunodeficiency (12), malignancy (9), diabetes (7), trauma (7), presence of a foreign body (6), and previous surgery (6). The clostridia were the only bacterial isolates in 14 (15%) cases; 82 (85%) cases had mixed infection. The species most commonly isolated with clostridia were anaerobic cocci (57), Bacteroides spp. (B. fragilis group) (50), Escherichia coli (22), pigmented Prevotella and Porphyromonas spp. (18), and Fusobacterium spp. (10). Most Bacteroides and E. coli isolates with clostridia were from abdominal infections and skin and soft tissue infections adjacent to the rectal area; most pigmented Prevotella and Porphyromonas isolates were from oropharyngeal, pulmonary, and head and neck sites. Antimicrobial therapy was given to all patients, in conjunction with surgical drainage in 34 (35%). Only two patients died. GRAM-POSITIVE NON-SPORE-FORMING BACILLI Anaerobic gram-positive non-spore-forming rods make up part of the microflora of the gingival crevices, gastrointestinal tract, vagina, and skin.7 Because many of them appear

Anaerobes as Pathogens in Childhood

C. difficile

C. innocuum

C. limosum

C. paraputrificum

7

C. C. perfringens ramosum

Clostridium spp.

1

1 3 2 2 1

3 1 2 1 1 1 1

1

16 4

3 1

1 1 1 1

1

21

1

41 9 1 2

2 5 2

3 7 3

1 1 7 3 43

1 1 4 29 3 113

1

1

4

3

5

1

1

Total

2 6

1 5

37

13

to be similar morphologically, they have been difficult to separate by the usual bacteriologic tests. Several distinct genera are recognized: Actinomyces, Arachnia, Bifidobacterium, Eubacterium, Lactobacillus, and Propionibacterium. The Actinomyces, Arachnia, and Bifidobacterium of the family Actinomycetaceae are gram-positive, pleomorphic, anaerobic-to-microaerophilic bacilli. Species of the genus Bifidobacterium are part of the commensal flora of the mouth, gastrointestinal tract, and female genital tract and constitute a high proportion of the normal intestinal flora in humans, especially in breast-fed infants.21 Although some infections caused by these organisms have been reported,22–25 little is known about their pathogenic potential. Eubacterium spp. are part of the flora of the mouth and the bowel. They have been recognized as pathogens in chronic periodontal disease26 and in infections associated with intrauterine devices27; they have also been isolated from patients with bacteremia associated with malignancy28 and from female genital tract infection.29 Lactobacillus spp. are ubiquitous inhabitants of the human oral cavity, the vagina, and the gastrointestinal tract.30 They have been implicated in various serious deep-seated infections, amnionitis,30 and bacteremia.31 Eubacterium, Lactobacillus and Bifidobacterium spp. have been isolated in pure culture in only a few instances and are usually isolated in mixed culture from clinical specimens.1 The infections where they have been found most often are chronic

8

Chapter 1

otitis media and sinusitis, aspiration pneumonia, and intra-abdominal, obstetric, and gynecologic and skin and soft-tissue infections.1,32 A retrospective review has summarized our experience of the isolation of Bifidobacterium, Eubacterium, and strictly anaerobic Lactobacillus spp. from infections in children over a 20-year period. From 1974 to 1994, a total of 2033 microbiologic specimens from children were submitted for cultures for anaerobic bacteria. Fifty-seven isolates of Bifidobacterium spp. were obtained from 55 (3%) children, 67 isolates of Eubacterium spp. from 65 (3%) children, and 41 isolates of Lactobacillus spp. from 40 (2%) children (Table 1.4)33 Most Bifidobacterium isolates were from chronic otitis media, abscesses, peritonitis, aspiration pneumonia, and paronychia. Most Eubacterium isolates

Table 1.4 Isolates of Bifidobacterium, Eubacterium, and Lactobacillus from Clinical Specimens in Children Number of isolates of

Total Source: Ref. 33.

1 1

2 1

3 1 2

2

1 1

1 3 1

1

2 1

2 2

6 25 33 75 180 39 22 58 116 129

1

3 2

2 1

7 2 1

1780 5 19 33 57 6 1

14 4 1

1

3

4

1

1 6

8

1 1

1 2

2

2

1 3

1 4

2 1 3

1 2 1 4

2 8 4 1

2 1

1

2 2 3 2 1 1 3 1 1 4 7 10 17 1 2

6 11 42 67

1

1 2 3

1

Total

74 10

Lactobacillus spp.

3

L. acidophilus

2

2

L. catenaforme

1

2

1

L. fermfentum

7 11 23

2 24 28

L. jensenii

142 5 24 24

1

L. minutus

2

1

Total

1

Eubacterium spp.

1

E. lentum

7

E. limosum

6

Lactubacillus

E. moniloforme

1

E. multiforme

Total

428 342 53

E. tenue

Bifodobacterium spp.

Abscess Bacteremia Cervical lymphadenitis Ears: chronic otitis media chronic mastoiditis Cholesteatoma Pulmonary: Aspiration pneumonia Lung abscess Pneumonia in cystic fibrosis Tracheostomy site Paronychia Wounds Burns Bites Gastrostomy site Decubitus ulcers Peritonitis Conjunctivitis

B. dentium

Type of Infection

Eubacterium

B. adolescentis

Total specimens examined

Bifidobacterium

5 30 41

Anaerobes as Pathogens in Childhood

9

were from abscesses, peritonitis, decubitus ulcers, and bites. Lactobacillus spp. were mainly isolated from abscesses, aspiration pneumonia, bacteremia and conjunctivitis. Most (> 90%) infections from which these species were isolated were polymicrobial and yielded a mixture of aerobic and anaerobic bacteria. The organisms most commonly isolated with the non-spore-forming anaerobic gram-positive rods were Peptostreptococcus spp., Bacteroides spp., pigmented Prevotella and Porphyromonas spp., Fusobacterium spp., Staphylococcus aureus and E coli. Most Bacteroides spp. and E. coli were isolated from intra-abdominal infection and skin and soft tissue infection around the rectal area, whereas most Prevotella, Porphyromonas, and Fusobacterium isolates were from oropharyngeal, pulmonary and head and neck sites. The predisposing conditions associated with the isolation of non-spore-forming anaerobic gram-positive rods were previous surgery, malignancy, steroid therapy, and immunodeficiency. Antimicrobial therapy was given to 149 (83%) of the 160 patients, in conjunction with surgical drainage or correction of pathology in 89 (56%). Actinomyces israelii and Actinomyces naeslundii are normal inhibitants of the human mouth and throat (particularly gingival crypts, dental calculus, and tonsillar crypts) and are the most frequently isolated pathogenic actinomycetes. These organisms have been recovered from intracranial abscesses,34 chronic mastoiditis,16 aspiration pneumonia,35 and peritonitis.18 Although actinomycetes often are present in mixed culture, they are clearly pathogenic in their own right and may produce widespread, devastating disease anywhere in the body.36 The lesions of actinomycosis occur most commonly in the tissues of the face and neck, lungs, pleura, and ileocecal regions. Bone, pericardial, and anorectal lesions are less common, but virtually any tissue may be invaded; a disseminated, bacteremic form has been described. Propionibacterium spp. are part of the normal bacterial flora that colonize the skin,37 conjunctiva,38 oropharynx, and gastrointestinal tract.39 These non-spore-forming anaerobic gram-positive bacilli are frequent contaminants of specimens of blood and other sterile body fluids and have been generally considered to play little or no pathogenic role in humans. Propionibacterium acnes and other Propionibacterium spp. have, however, been recovered with or without other aerobic or anaerobic organisms as etiologic agents of conjunctivitis,40 intracranial abscesses,41,42 peritonitis,43 as well as dental, parotid,44 pulmonary,35 and other serious infections.45 They have often been recovered as a sole isolate in specimens obtained from patients with infections associated with a foreign body (such as an artificial valve), endocarditis,46,47 and central nervous system (CNS) shunt infections.46,48 The possible role of P. acnes in the pathogenesis of acne vulgaris was suggested. The data that support this are based on the recovery of this organism in large numbers from sebaceous follicles, especially in patients with acne; on its ability to elaborate enzymes such as lipase, protease, and hyaluronidase; and on its ability to activate the complement system and enhance chemotactic activity of neutrophils.49 The summary of our experience over a period of 15 years in the recovery of Propionibacterium spp. from infections in children50 highlights the importance of Propionibacterium spp. as an unusual but potentially important, pathogen in children. A total of 368 isolates of Propionibacterium spp. were recovered from 2003 specimens studies for the identification of anaerobic bacteria in children during a 15-year period (1973 to 1988) (Table 1.5). Of these, 343 (89%) were P. acnes. A total of 51 (14%) Propionibacterium isolates identified from 45 patients were considered to cause infection. Clinically significant infections caused by Propionibacterium spp. were associated with

10

Chapter 1

Table 1.5 Clinical and Microbiologic Data in 45 Children with Significant Propionibacterium Infection Infection

No. of Isolates

Abscess

8

Blood

10

Burn Bone

4 2

Cyst Central nervous system

1 5

Ear

8

Eye Lymph gland

1 5

Mastoid Sinus Tumor

1 1 2

Wound

3

Types of Infection (no. patients) Subcutaneous abscess (4), renal (2), parotid (1), neck (1) Bacteremia (10)

Leg (2), chest (1), arm (1) Chronic osteomyelitis: scapula (1), femur (1) Renal (1) Meningovertriculitis (4), brain abscess (1) Acute otitis (3), chronic otitis (3), cholesteatoma (2) Posttraumatic endophthalmitis (1) Cervical adenitis (2), inguinal node (1), fermoral (1), axillary nodes (1) Mastoiditis (1) Frontal sinusitis (1) Mediastinal neuroblastoma (1) retroperitoneal lymphoma (1) Abdomen (1), neck (1), scalp (1)

Predisposing Conditions (no. patients) Diabetes (1), immunodeficiency (1) In-dwelling vascular catheters (5),a ventriculoatrial shunt (2), prosthetic valve (1) Diabetes (1) Metal rod after fracture (2) Immunodeficiency (1) Ventriculoatrial shunt (2),b ventriculoperitoneal shunt (2), sinusitis (1) Diabetes (1), steroid therapy (1), ear tubes (3) Sickle cell anemia (1)

Diabetes (1)

Postsurgical (4), diabetes (1), hypogammaglobulinemia (1), malignant melanoma (1)

a

Local cellulitis in three cases. Bacteremia in two cases. Source: Ref. 50.

b

bacteremia in 10 children; ear infection in 8; abscesses in 8; adenitis and central nervous system infection in 5 each; burns in 4; wounds in 3; tumors and bone in 2 each; and cysts, eye, sinus, and mastoid in one each. Predisposing or underlying conditions were present in 33 children (73%). These included the presence of a foreign body (17), immunodeficiency (6), malignancy (5), diabetes (5), previous surgery (4), and steroid therapy (2). Antimicrobial therapy was given to 41 (91%) children. Surgical drainage was concomitantly performed in 22 (49%). Four patients died. GRAM-NEGATIVE BACILLI The anaerobic gram-negative bacilli (AGNB) are differentiated into genera on the basis of the fermentation acids they produce. The family Bacteroidaceae contains several genera of medical importance: Bacteroides fragilis group, Prevotella, Porphyromonas, Bacteroides, and Fusobacterium.

Anaerobes as Pathogens in Childhood

11

Bacteroides fragilis Group The relative distribution of the different members of the B. fragilis group has important clinical implications in the management of infections involving anaerobic bacteria. This is because of the different antimicrobial susceptibility of various organisms within this group. Although members of B. fragilis group produce beta-lactamase and resist penicillin, their susceptibility to cephalosporins is variable1 but predictable. The B. fragilis group is the species of Bacteroidaceae that occur with greatest frequency in clinical specimens. These organisms are resistant to penicillin by virtue of production of beta-lactamase and by other unknown factors.51 Thess organisms were formerly classified as subspecies of B. fragilis (i.e. ss. fragilis, ss. distasonis, ss. ovatus, ss. thetaiotaomicron, and ss. vulgatus). They have been reclassified into distinct species on the basis of DNA homology studies.52 B. fragilis (formerly known as B. fragilis ss. fragilis, one of the subspecies of B. fragilis) is the anaerobe most frequently isolated from infections. Although the B. fragilis group is the most common species found in clinical specimens, it represents only 0.5% of the bacteria present in stool. The virulence of this group of organisms results from a variety of features that include the ability to produce capsular material, which is protective against phagocytosis.53 Because of its presence in the normal flora of the gastrointestinal tract, this organism is predominant in bacteremia associated with intraabdominal infections,1 peritonitis, abscesses following rupture of a viscus,18 and subcutaneous abscesses or burns near the anus.54,55 Although B. fragilis is not generally found as part of the normal oral flora, it can colonize the oral cavity of patients with poor oral hygiene or those who previously received antimicrobial therapy, especially penicillin. Following the colonization of the oropharyngeal cavity, these organisms also can be recovered from pediatric infections that originate in this area, such as aspiration pneumonia,35 lung abscesses,56 chronic otitis media,14 brain abscesses,34 and subcutaneous abscesses or burns near the oral cavity.54,55 B. fragilis can be recovered from infectious processes in the newborn. The infant is at risk of developing these infections when born to a mother with amnionitis or premature rupture of membranes or as a result of its passage through the birth canal, where B. fragilis can be part of the normal flora.57 B. fragilis was recovered from newborns with aspiration pneumonia,58 bacteremia,11 omphalitis,59 and subcutaneous abscesses and occipital osteomylitis following fetal monitoring.60 Bilophila Wadsworthia and Centipeda periodontii are new genuses and species found in abdominal and oral infections. Bacteroides ureolyticus (formerly called Bacteroides corrodens and related to Campylobacter) characteristically forms small colonies with a zone around or under the colony that has been described as “pitting” of the agar: thus its former name, corrodens. B. ureolyticus is part of the normal flora of the mouth and has been isolated from blood cultures from patients shortly after dental surgery and from those with periodontal abscesses, aspiration pneumonia,35 and lung abscesses.56 We have summarized the recovery of organisms of the B. fragilis group from pediatric patients from 1974 to 1990; a total of 336 Bacteroides isolates were obtained from 312 specimens from 274 patients61 (Table 1.6). They comprised 180 (54%) B. fragilis, 55 (16%) B. thetaiotaomicron, 36(11%) B. vulgatus, 34 (10%) B. distasonis, 21 (6%) B. ovatus, and 10 (3%) B. uniformis isolates. Infections in 253 (92%) patients were polymicrobial, but in 21 (8%) children, a Bacteroides sp. was isolated in pure culture. Bacteroides isolates were recovered from peritoneal fluid (114), abscesses (110), wound infections

12

Chapter 1

Table 1.6 Bacteroides fragilis group Isolates from 312 Specimens from 274 Children Number of Specimens

Type of infection Peritoneal fluid Abscess Wounds Decubitus ulcers Omphalitis Burns Bites, human Blood Ear: mastoiditis, otitis, chronic otitis, cholesteatoma Pneumonia Empyema Sinusitis, chronic Osteomyelitis Conjunctivitis Urinary tract infection Total

Total

with Bacteroides spp.

with B. fragilis alone

115 321 75 58 25 180 18 334

108 101 24 9 6 5 1 13

24 94 38 80 72 45 26 148 5

3 8 6 13 7 1 3 1 3

1 1

1 4 3 4 3 1 2 1 2

1658

312

22

180

2

12

3 3

B. fragilis 63 61 13 4 4 4 10

Source: Ref. 61.

(29), blood cultures (13) and patients with pneumonia (14) or chronic otitis media (8). Predisposing conditions were present in 145 (53%) children; these were previous surgery (46), trauma (28), malignancy (21), prematurity (19), immunodeficiency (18), steroid therapy (12), foreign body (10), diabetes (9) and sickle cell disease (7). The microorganisms isolated most commonly mixed with Bacteroides spp. were anaerobic cocci (221), E. coli (122), Fusobacterium spp. (38), and Clostridium spp. (30). All patients received antimicrobial therapy and surgical drainage; correction of pathology was also performed in 197 (72%) cases. All but 12 (5%) patients recovered. Prevotella oralis is part of the normal flora of the mouth and vagina. Unlike B. fragilis, however, strains of P. oralis generally are susceptible to penicillin and the cephalosporins, although more strains of P. oralis have shown resistance to these drugs. P. oralis almost never is found in pure culture in clinical infection. This organism can possess a capsule.62 It has been recovered from almost all types of respiratory tract and subcutaneous infections in children, including aspiration pneumonia,35 lung abscess,56 chronic otitis media,14 sinusitis,15 and subcutaneous abscesses around the oral cavity,54 where most P. oralis isolates have been recovered. Pigmented Prevotella and Porphyromonas requires the presence of both hemin and vitamin K1 for growth.63 The requirement for vitamin K1 in vivo often is met by coexistence with organisms that are capable of supplying this need. Pigmented Prevotella and Porphyromonas are part of the normal oral and vaginal flora7 and are the predominant anaerobic gram-negative bacilli isolated from respiratory infections. These include aspiration

Anaerobes as Pathogens in Childhood

13

Number of Bacteroides Isolates B. distasonis

B. vulgatus

B. ovatus

B. thetaiotaomicron

B. uniformis

5 11 4 2

9 13 2 2 1

11 6 3

16 19 7 2 2 1

10

1 1 2 3 1 3 1

2

3

1

1

1 34

36

21

55

114 110 29 10 7 5 1 13 3 8 6 14 7 1 4 1 3

1 1

1 7

Total

10

336

pneumonia,35 lung abscess,56 chronic otitis media,14 and chronic sinusitis.15 They have been recovered also from abscesses and burns around the oral cavity54 and from human bites,64 paronychia,65 urinary tract infections,66 brain abscesses,34 and osteomyelitis.67 Also, they have been isolated from children with bacteremia associated with infections of the upper respiratory tract.11 Pigmented Prevotella and Porphyromonas have been found to play a major role in the pathogenesis of periodontal disease68 and periodontal abscesses in children.69 Porphyromonas asaccharolytica is the most frequent clinical isolate of all pigmented Prevotella and Porphyromonas spp. Prevotella intermedia is identified somewhat less frequently, and Prevotella melaninogenica is the least common. The presence of capsular material suppresses phagocytosis and therefore is an important factor influencing the pathogenicity of pigmented Prevotella and Porphyromonas.62,70 Porphyromonas gingivalis is very similar to P. asaccharolytica; only the production of phenylacetic acid by P. gingivalis differentiates them.68 P. gingivalis is an important isolate in periodontitis.68 We have summarized our experience in recovery of Prevotella and Porphyromonas over a period of 20 years71 (1974 to 1994). The data illustrate the spectrum and importance of Prevotella and Porphyromonas spp. in infections in children. A total of 504 isolates of Prevotella and Porphyromonas spp. were obtained from 435 (21%) of 2033 specimens obtained from 418 children (Table 1.7). They included 160 (32%) P. melaninogenica, 105 (21%) P. intermedia, 84 (17%) P. asaccharolytica, 58 (12%) P. oris-buccae, and 58 (12%) P. oralis. Most Prevotella and Porphyromonas species were isolated from

14

Table 1.7 Prevotella and Porphyromonas Isolates from 435 Specimens from 418 Children Number of Specimens

Type of Infection

Source: Ref. 71

With Prevotella and Porphyromonas spp. Alone

428 342

136 3

4 2

142 24 24 64

55 12 5 4

2

74 72 14 10 17 6

62 6 3 3 2 1

1

75 25 22 33 39 180 58 58 116 26 45 129 10 2033

12 15 8 15 10 12 2 4 36 13 12 3 1 435

Number of Isolates of P. melaninogenica

P. intermedia

P. oralis

P. orisbuccae

18

53 1

30 1

16

26

33 1

20 6 1 3

11 3 2 2

10 2 1

5 1 1

12 2

13 2 1

14 3 2 2 1

9

13 1

6

1 2 1 2 2 1

2 1 1 7

2 1 14

P.

Prevotella spp.

39

4 5 2 4 4 6 2 3 12 6 6 2 1 160

5 3 3 3 4 2 1 8 1 3 1 105

12 1 1

1

2 5 2 4 3

asaccharolytica

3 2 4

1 1

2 1

6 3 2

1

5 3 2

58

58

84

Chapter 1

Abscess Bacteremia Ears: Chronic otitis media Chronic mastoiditis Cholesteatoma Serous otitis media Pulmonary: Aspiration pneumonia Empyema Tracheitis Ventilator pneumonia Tracheostomy pneumonia Pneumonia in cystic fibrosis Wounds: Postsurgical Tracheostomy site Gastrostomy site Paronychia Bites Burns Diaper dermatitis Decubitus ulcers Peritonitis Osteomyelitis Sinusitis, chronic Conjunctivitis Urinary tract Total

Total

With Prevotella and Porphyromonas spp.

Anaerobes as Pathogens in Childhood

15

abscesses (176), pulmonary infections (85), ear infections (82), wound infections (44), peritonitis (38), paronychia (15), and chronic sinusitis (14). Predisposing conditions were noted in 111 (27%) of the cases; these included previous surgery in 41 (10%), foreign body in 36 (9%), neurologic deficiencies in 29 (7%), immunodeficiency in 21 (5%), steroid therapy in 12 (4%), diabetes in 8 (2%), and malignancy in 7 (2%). Prevotella and Porphyromonas spp. were the only isolates in 14 (3%) patients, and mixed infection was encountered in 404 (97%). The microorganisms most commonly isolated with Prevotella and Porphyromonas spp. were anaerobic cocci (393 isolates). Fusobacterium spp. (108), Bacteroides spp. (B. fragilis group) (95), E. coli (56) and other gram-negative anaerobic bacilli52. B. fragilis and E. coli were isolated from intra-abdominal infections and skin and soft tissue infections around the rectal area, whereas most Fusobacterium species were isolated from oropharyngeal, pulmonary and head and neck sites. Beta-lactamase production was detected in 191 (38%) Prevotella and Porphyromonas isolates from all body sites. All patients received antimicrobial therapy, and surgical drainage was performed in 173 (41%) cases. Four patients died from their infection. Bacteroides ruminicola ss. brevis also has been recovered from these sites,35,56 as well as from peritonsillar abscesses,17 chronic sinusitis,15 mastoiditis,16 and peritonitis.18 B. ruminicola has recently been divided into Prevotella buccae and Prevotella oris according to their beta-glucosidase activity.63 P. oris strains are generally more resistant to penicillin than P. buccae. Prevotella bivia and Prevotella disiens are important isolates in obstetric and gynecologic infections. They account for 9% and 1% of all anaerobic gram-negative bacillary isolates. Fusobacterium Species Cells of Fusobacterium species are moderately long and thin with tapered ends; they have typical fusiform morphology. The species of Fusobacterium seen most often in clinical infections are Fusobacterium nucleatum, Fusobacterium necrophorum, Fusobacterium mortiferum, and Fusobacterium varium. Fusobacterium nucleatum is the predominant Fusobacterium from clinical specimens, often associated with infections of the mouth, lung,35 and brain.34 They are often isolated from abscesses, obstetric and gynecologic infections, chest infections, blood, and wounds. We have reviewed our records of the isolation of Fusobacterium species in children over 15 years (1973–1988)72. A total of 243 strains of Fusobacterium spp. were recovered from 226 of 1399 (16%) specimens obtained from 213 children (Table 1.8). These included 65 (27%) Fusobacterium sp., 144 (59%) F. nucleatum, 25 (10%) F. necrophorum, 5 (2%) F. varium, 3 (1%) F. mortiferum, and one (0.4%) Fusobacterium gonidiaformans. Most Fusobacterium spp. were recovered from patients with abscesses (100), aspiration pneumonia (24), paronychia (15), bites (14), chronic sinusitis (10), chronic otitis media (9), and osteomyelitis (8). Predisposing conditions were noted in 32 (15%) of the cases. These included immunodeficiency in 9 (4%), steroid therapy in 8 (4%), previous surgery in 6 (3%), diabetes in 6 (3%) and malignant neoplasms in 5 (2%). Fusobacterium sp. was the only isolate in 16 (8%) instances, while mixed infections were encountered in 197 (92%). The organisms most commonly isolated with Fusobacterium sp. were anaerobic cocci (155), pigmented Prevotella sp. and Porphyromonas species (95), B. fragilis group (80), and E. coli (43). Most strains of B. fragilis group and E. coli were recovered from intra-abdominal infections and skin and soft tissue infections proximal to the rectal area.

16

Table 1.8 243 Fusobacterium Species Isolated from 213 Specimens Obtained from Children

Total Number of Specimens Abscess Aspiration pneumonia Bacteremia Bites Burns Cholesteatoma Chronic otitis media Chronic sinusitis Conjunctivitis Decubitus ulcers Empyema Mastoiditis Omphalitis Osteomyelitis Paronychia Peritonitis Total

420 74 42 39 180 24 94 45 129 58 72 24 23 26 33 116

92 22 3 13 2 2 8 9 3 5 6 2 3 8 13 35

7 1 3

1399

226

16

Number of Fusobacteria Isolated Fusobacterium species not Speciated 28 5 4

3

1 1

5 4 2 1

F. nucleatum

F. necrophorum

F. mortiferum

F. gonidiaformans

54 18 3 9 2 2 4 6

16

1 1

1

F. varium

1

1 4 5

1 2

3 4 9

3 5 9 20

2 3

1

65

144

25

3

4 1

5

Chapter 1

Source: Ref. 79

Total Number with with Fusobacterium Fusobacterium sp. sp. Alone

Anaerobes as Pathogens in Childhood

17

Most pigmented Prevotella and Porphyromonas sps. were recovered from oropharyngeal and pulmonary sites and from sites around the head and neck. Antimicrobial therapy was administered to all patients; surgical drainage was performed in 85 (40%). All, except two patients who died, recovered. Because these organisms are part of the normal oral and gastrointestinal flora, they are found in almost all types of infections in children. These include bacteremia,11 meningitis associated with otologic diseases,14 peritonitis following rupture of a viscus,18 and subcutaneous abscesses and burns near the oral or anal orifices.54,55 Antimicrobial Resistance of Gram-Negative Bacilli It is evident that the B. fragilis group is the most prevalent of the Bacteroidaceae that have been isolated. B. fragilis is the most prevalent organism in the B. fragilis group, accounting for 41% to 78% of the isolates of the group. However, it should be remembered that the other members of the group account for the rest of the B. fragilis group isolates. This is of particular importance because these members are more resistant than B. fragilis to the newer cephalosporins. The growing resistance of anaerobic gram-negative bacilli previously susceptible to penicillins has been noticed in the last decade.74,75 These are members of the pigmented Prevotella and Porphyromonas spp.—P. oralis, P. disiens, P. bivia, P. oris-buccae, and Fusobacterium. The main mechanism of their resistance is through the production of the enzyme beta-lactamase. Complete identification and susceptibility testing and ability to produce beta-lactamase in members of the B. fragilis group as well as other anaerobic gram-negative bacilli are helpful in making choices between antimicrobials for the therapy of infections involving these organisms. The recovery rate of the different AGNB from infected sites is similar to their distribution in the normal flora.1,7,39 While the B. fragilis group were more often isolates in sites proximal to the gastrointestinal tract (abdomen, bile), pigmented Prevotella, Porphyromonas, and Fusobacterium spp. were more prevalent in infections proximal to the oral cavity (bones, sinuses, chest), and P. bivia and P. disiens were more often isolates in obstetric and gynecologic infections. Knowledge of this common mode of distribution allows for logical choice of antimicrobials adequate for the therapy of infections in these sites. GRAM-POSITIVE COCCI Anaerobic cocci have been most often reported either as “anaerobic streptococci” or “anaerobic gram-positive cocci.” These organisms were previously divided into Peptococcus and Peptostreptococcus spp. However, they are currently all named Peptostreptococcus sp. and further divided according to species primarily on the basis of their metabolic products. The species most commonly isolated are Peptostreptococcus magnus (18% of all anaerobic gram-positive cocci isolated in our hospitals), Peptostreptococcus asaccharolyticus (17%), Peptostreptococcus anaerobius (16%), Peptostreptococcus prevotii (13%), and Peptostreptococcus micros (4%).2 The infectious sites where anaerobic cocci predominate are, in descending order of frequency, ear, bone, cysts, obstetric and gynecologic sites, abscesses, and sinuses. These organisms are part of the normal flora of the mouth, upper respiratory tract, intestinal tract, vagina, and skin. Their presence has been documented in adults in a variety of syndromes, including endocarditis, brain abscesses, puerperal sepsis, traumatic wounds, and postoperative necrotizing fasciitis.1 They have been recovered in pediatric infections as well as in subcutaneous abscesses and burns around the oral and anal

18

Chapter 1

area,54,55 intra-abdominal infections,18 and decubitus ulcers.76 They also have been isolated as causes of bacteremia11 and brain abscesses.34,73 These organisms are predominant isolates also in all types of respiratory infections, including chronic sinusitis,15 mastoiditis,16 acute77 and chronic14 otitis media, aspiration pneumonia,35 and lung abscess.56 They generally are recovered mixed with other aerobic or anaerobic organisms, but in many cases they are the only pathogens recovered. This may be of particular significance in cases of bacteremia11 or acute otitis media.76 We have recovered 680 Peptostreptococcus spp. from 598 (34%) of 1750 specimens obtained from 554 pediatric patients over a period of 15 years (1973 to 1988) (Table 1.9).78 They included 103 Peptostreptococcus asaccharolyticus, 74 Peptostreptococcus magnus, 56 Peptostreptococcus prevotii, 51 Peptostreptococcus micros, 46 Peptostreptococcus anaerobius, 11 Peptostreptococcus morbilorium, and 10 Peptostreptococcus saccharolyticus. Most infections were polymicrobial (in 553 instances, or 92%); but in 45 (8%), Peptostreptococcus was recovered in pure culture. Most Peptostreptococcus specimens were isolated from abscesses (237), ears (104), peritoneal fluid (95), lung infections (66), bone (30), and sinuses (24). Predisposing conditions were present in 224 (40%) children. These were previous surgery (54), immunodeficiency (43), malignancy (35), trauma (34), diabetes (23), prematurity (22), steroid therapy (19), foreign body (10) and sickle cell anemia (7). The organisms most commonly isolated with Peptostreptococcus were AGNB sp. (276, including 190 of the B. fragilis group), Prevotella sp. (159), Fusobacterium sp. (122), Escherichia coli (114), and Staphylococcus aureus (97). Antimicrobial therapy was administered to all but 14 patients. Surgical drainage or correction of pathology was performed in 307 (56%) patients; 10 patients (2%) died of their infection. Microaerophilic streptococci (MS) are not true anaerobes, as they can become aerotolerant after subculture; however, they grow better anaerobically and are often grouped under anaerobes in many studies. These organisms include the Streptococcus intermedius group (previously called the Streptococcus milleri group, which include Streptococcus angiosus, Streptococcus constellatus, and Streptococcus intermedius), and Gemella morbillorum (previously called Streptococcus morbillorum. MS are of particular importance in chronic sinusitis14 and brain abscesses.34,73 They have also been recovered from obstetric and gynecologic infections and abscesses. We summarized our experience in recovery of MS from children over a period of 15 years (1974 to 1989).80 A total of 148 isolates (including 47 of of S. constellatus, 43 of S intermedius, and 5 of G morbillorum were cultured from 123 children (Table 1.10). There were predisposing conditions in 47 (38%) patients, of which most common were previous surgery (14), trauma (11), malignancy (9), diabetes (6) and immunodeficiency (5). MS were the only bacteria isolated from 12 (10%) patients, and mixed infections were encountered in 111, where the number of isolates varied between 2 and 7 (average 3.0) isolates per specimen. The bacteria most commonly isolated with MS were anaerobic cocci (70 isolates), B. fragilis group (54), pigmented Prevotella and Porphyromonas (34), and E. coli (26). Most B. fragilis and E. coli organisms were recovered from intra-abdominal infections and infections of skin and soft tissue adjacent to the rectum. Most specimens of pigmented Prevotella and Fusobacterium were isolated from oropharyngeal, pulmonary, and head and neck sites. Most MS were recovered from abscesses (43%) and infections of the abdominal cavity (17%), sinuses (10%), and chest (9%). Antimicrobial therapy was administered to all patients, in 61 this was combined with surgical drainage or correction. Three patients died.

Number of Specimens

Abscesses Bites Blood Burn Conjunctivitis Decubitus ulcers Empyema Omphalitis Otitis (acute) Otitis (chronic) cholesteatoma mastoiditis Otitis (serous) Peritonitis Pneumonia Osteomyelitis Sinusitis Urinary tract Total

Number of Isolates

With P. alone

P. sp.

P. asacch.

95 18 2 10 27 10 4 2 19 21 6 10

57 4 1 6

Total

With P.

538 39 34 180 148 59 72 25 218 94 24 24 23 115 80 27 45 5

205 25 6 22 24 19 8 4 26 36 10 18 4 82 60 26 22 1

15 4

1 1 2

51 40 10 4

1750

598

45

329

6 5 1 7 2

1

P. morbil. 3 1 2 1

1 4 1 2 3 8 5 5 5 1 103

P. prevotii 22

4

19

P. micros

P. magnus

15

22 5 1 6

3 1

2 2

2 2 1 2 1 15 4

3 5

1 3 1 2

1

1 2 3 2 2 1 2 7 5 3

11

56

3

P. P. sacch. anaerobius

1 1 1 2

1 4 1 1 1 3 2

1

3 6 3 1

10

46

3

5

12 2 7 4

51

74

total P. 237 27 6 27 29 22 8 4 28 38 13 20 5 95 66 30 24 1

Anaerobes as Pathogens in Childhood

Table 1.9 680 Peptostreptococcus (P) Species in 598 Specimens Obtained from Children

680

Source: Ref. 78.

19

20

Chapter 1

Table 1.10 Microaerophilic Streptococci Recovered from 123 Children

Source

Total number of specimens

Abdomen Abscess Blood Burn Chest CNS Eye Ears Parotid gland Mastoids Sinuses Wounds Total

Number of with Microaerophilic S. S. G. MS streptococci constellatus intermedius morbillorum

136 487 346 180 115 184 132 211 26 24 46 75

23 55 4 4 13 5 2 1 3 3 14 4

2 30 2

1962

131

53

4 1 1 3 1 9

17 13 1 2 6 1

6 20 1 2 4 3 2

4 3

2 2 1

47

43

4 1

5

Source: Ref. 80.

GRAM-NEGATIVE COCCI Three species are described as anaerobic gram-negative cocci: Veillonella, Acidaminococcus, and Megasphaera. There are two described species of Veillonella and only one each of the other two genera. The veillonellae are the most frequently involved of the three species and are part of the normal flora of the mouth, vagina, and the small intestine of some persons.7 Veillonella spp. are found infrequently in children, mostly in association with mixed infections, and are recovered mixed with mouth and bowel flora. Although they rarely are isolated from clinical infections, these organisms have been recovered occasionally from almost every type of pediatric infection. Their exact pathogenic role is unclear, however. We have summarized our experience in isolation of Veillonella spp. from children over a period of 15 years (1974 to 1999). A total of 2033 specimens from children were submitted for culture of anaerobic bacteria (Table 1.11). Eighty-three isolates of Veillonella spp. were recovered from 83 children (4%).81 Most Veillonella spp. were recovered from abscesses, aspiration pneumonias, burns, bites, and sinuses. The infections were polymicrobial in 79 (95%) patients, but in 4 (5%) patients, Veillonella spp. were recovered in pure culture. The predisposing conditions associated with the recovery of these organisms were previous surgery, malignancy, steroid therapy, foreign body, and immunodeficiency. CONCLUSION Many infectious diseases in children can be produced by anaerobic bacteria. Anaerobes of major clinical importance tend to follow certain predictable patterns, according to anatomic sites and their virulence. In the upper respiratory passages and lung, the major anaerobic pathogens are Peptostreptococcus spp., pigmented Prevotella and Porphy-

Anaerobes as Pathogens in Childhood

21

TABLE 1.11 Veillonella Isolates in 83 Specimens from Various Clinical Specimens from Children

Source of Infection Abscess Cervical lymphadenitis Chronic mastoiditis Serous otitis media Pulmonary Aspiration pneumonia Empyema Ventilator pneumonia Pneumonia in cystic fibrosis Wounds Tracheostomy site Paronychia Wounds Burns Bites Gastrostomy site Omphalitis Peritonitis Osteomyelitis Sinusitis, chronic Total

Total No. of Specimens

Total No. (%) of Veillonella spp.

428 53 24 64

29 (6.8) 2 (3.8) 1 (4.2) 1 (1.6)

74 72 10 6

12 (16.2) 1 (1.4) 1 (10) 2 (33.3)

25 33 75 180 39 22 23 116 26 45

3 (12.0) 1 (3.0) 3 (4.0) 7 (3.9) 7 (17.9) 2 (9.1) 1 (4.3) 3 (2.6) 1 (3.8) 6 (13.6)

1,315

83 (6.3)

Source: Ref. 81.

romonas spp. and Fusobacterium spp. In intraabdominal infections and female genital infections, the most frequent isolates are of the B. fragilis group followed by anaerobic gram-positive cocci and Clostridium species. Recognition of the pathogenic features of these organisms enables prompt identification and initiation of appropriate management of the infections that they cause. REFERENCES 1. Finegold, S.M.: Anaerobic Bacteria in Human Disease. New York: Academic Press; 1977. 2. Brook, I.: Recovery of anaerobic bacteria from clinical specimens in 12 years at two military hospitals. J. Clin. Microbiol. 26:1181, 1988. 3. Howard, M.F., et al.: Outbreak of necrotizing enterocolitis caused by Clostridium butyricum. Lancet. 2:1099, 1977. 4. Brook, I.: Isolation of toxin producing Clostridium difficile from two children with oxacillin and dicloxacillin associated diarrhea. Pediatrics 65:1154, 1980. 5. Brook, I., et al: Clostridium difficile in pediatric infections. J. Infect. 4:253, 1982. 6. Fischer, M.G.W., Sunakorn, P., Duangman, C.: Otogenous tetanus: A sequela of chronic ear infections. Am. J. Dis. Child. 131:445, 1977.

22

Chapter 1

7. Rosebury, T.: Microorganisms Indigenous to Man. New York: McGraw-Hill, 1966. 8. Cashore, W.J., et al.: Clostridium colonization and clostridial toxin in neonatal necrotizing enterocolitis. J. Pediatr. 98:308, 1981. 9. Sturm, R., et al: Neonatal necrotizing enterocolitis associated with penicillin resistant Clostridium butyricum. Pediatrics 66:928, 1980. 10. Cooperstock, M.S., et al.: Clostridium difficile in normal infants and sudden infant death syndrome: an association with infant formula feeding. Pediatrics 70:91, 1982. 11. Brook, I., et al: Anaerobic bacteremia in children. Am. J. Dis. Child. 134:1052, 1980. 12. Brook, I., Gluck, R.S.: Clostridium paraputrificum sepsis in sickle cell disease: a report of a case. South. Med. J. 73:1644, 1980. 13. Brook, I., Schwartz, R.H., Controni, G.,: Clostridium ramosum isolation in acute otitis media. Clin. Pediatr. 18:699, 1979. 14. Brook, I.: Microbiology of chronic otitis media with perforation in children. Am. J. Dis. Child. 130:564, 1980. 15. Brook, I.: Bacteriological features of chronic sinusitis in children. J.A.M.A. 246:967, 1981. 16. Brook, I.: Aerobic and anaerobic bacteriology of chronic mastoiditis in children. Am. J. Dis. Child. 135, 1981. 17. Brook, I.: Aerobic and anaerobic bacteriology of peritonsillar abscess in children. Acta. Pediatr. Scand. 70:831, 1981. 18. Brook, I.: Bacterial studies of peritoneal cavity and postoperative surgical wound drainage following perforated appendix in children. Ann. Surg. 192:208, 1980. 19. Brook, I., Martin, W.J., Finegold, S.M.: Effect of silver nitrate application on the conjunctival flora of the newborn and the occurrence of clostridial conjunctivitis. J. Pediatr. Ophthalmol. Strabismus 15:173, 1978. 20. Brook, I.: Clostridial infection in children. J. Med.Microbiol. 42:78, 1995. 21. Sato, J., Mochizuki, K., Homma, N.: Affinity of the Bifidobacterium to intestinal mucosal epithelial cells. Bifidobact. Microfl. 1:51, 1982. 22. Gorbach, S.L., Thadepalli, H.: Clindamycin in pure and mixed anaerobic infections. Arch. Intern. Med. 134: 87, 1974. 23. O’Connor, J., MacCormick, D.E.: Mixed organism peritonitis complicating continuous ambulatory peritoneal dialysis. N.Z. Med. J. 95: 811, 1982. 24. Thomas, A.V., Sodeman, T.H., Bentz, R.R.: Bifidobacterium (Actinomyces) eriksonii infection. Am. Rev. Respir. Dis. 110:663, 1974. 25. Hata, D., et al.: Meningitis caused by Bifidobacterium in an infant. Pediatr. Infect. Dis. J. 7: 669, 1988. 26. Vincent, J.W., Falkler, W.A., Suzuki, J.B.: Systemic antibody response of clinically characterized patients with antigens of Eubacterium brachy initially and following periodontal therapy. J. Periodontol. 57: 625, 1986. 27. Hill, G.B., Ayers, O.M., Kohan, A.P.: Characteristics and sites and infection of Eubacterium nodatum. Eubacterium timidum, Eubacterium brachy, and other asaccharolytic eubacteria. J. Clin. Microbiol. 25:1540, 1987. 28. Fainstein, V., Elting, L.S., Bodey, G.P.: Bacteremia caused by non-sporulating anaerobes in cancer patients. A 12-year experience. Medicine (Baltimore) 68:151, 1989. 29. Brook, I.: Anaerobic bacterial bacteremia: 12-year experience in two military hospitals. J. Infect. Dis. 160:1071, 1989. 30. Cox, S.M., Phillips, L.E., Mercer, L.J., Stager, C.E., Waller, S., Faro, S.: Lactobacillemia of amniotic fluid origin. Obstet. Gynecol. 68: 134, 1986. 31. Sherman, M.E., et al.: Lactobacillus: An unusual case of splenic abscess and sepsis in an immunocompromised host. Am. J. Clin. Pathol. 88: 659, 1987. 32. Brook, I., Frazier, E.H.: Significant recovery of nonsporulating anaerobic rods from clinical specimens. Clin. Infect. Dis. 16: 476, 1993.

Anaerobes as Pathogens in Childhood

23

33. Brook, I.: Isolation of non-sporing anaerobic rods from infections in children. J. Med. Microbiol. 45:21, 1996. 34. Brook, I.: Bacteriology of intracranial abscess in children. J. Neurosurg. 54:484, 1981. 35. Brook, I., Finegold, S.M.: Bacteriology of aspiration pneumonia in children. Pediatrics 65:1115, 1980. 36. Drake, D.P., Holt, R.J.: Childhood actinomycosis: Report of 3 recent cases. Arch. Dis. Child. 51:979, 1976. 37. McGinley, K.J., Webster, G.F., Leyden, J.J.: Regional variations of cutaneous prionibacteria. Appl. Environ Microbiol. 35:62, 1978. 38. Brook, I., Pettit, T.H., Martin, W.J., Finegold, S.M.: Aerobic and anaerobic bacteriology of acute conjunctivitis. Ann. Ophthalmol. 11:13, 1978. 39. Gorbach SL. Intestinal microflora. Gastroenterology 60:1110. 1971. 40. Brook, I.: Presence of anaerobic bacteria in conjunctivitis associated with wearing contact lenses. Ann. Ophthalmol. 20:397, 1988 41. Heineman, H.S., Braude, A.I.: Anaerobic infection of the brain. Observations on eighteen consecutive cases of brain abscess. Am. J. Med. 35:682, 1963. 42. Mathisen, G.E., et al.: Brain abscess and cerebritis. Rev. Infect. Dis. 6:101, 1984. 43. Dunkle, L.M., Brotherton, T.J., Feigin, R.D.: Anaerobic infections in children: A prospective study. Pediatrics. 57:311, 1976. 44. Goldberg, M.H.: Corynebacterium: An oral-systemic pathogen. Report of cases. J. Oral. Surg. 29:349, 1971. 45. Kaplan, K., Weinstein, L.: Diptheroid infections of man. Ann. Intern. Med. 70:919, 1969. 46. Everett, E.D., Eickhoff, T.C., Simon, R.H.: Cerebrospinal fluid shunt infections with anaerobic diphtheroids (Propionibacterium species). J. Neurosurg. 44: 580, 1976. 47. Wilson, W.R., et al.: Anaerobic bacteremia. Mayo Clin. Proc. 47:639, 1972. 48. Beeler, B.A., et al.: Propionibacterium acnes: pathogen in central nervous system shunt infection. Report of three cases including immune complex glomerulo-nephritis. Am. J. Med. 61:935, 1976. 49. Brown, S.K., Salita A.R.: Acne vulgaris. Lancet 351:1871, 1988. 50. Brook, I.: Infection caused by Propionibacterium in children. Clin. Pediatr. 33:486, 1994. 51. Olson-Liljequest, B., Dornbusch, K., Nord, C.E.: Characterization of three different beta-lactamases from the Bacteroides fragilis group. Antimicrob. Agents Chemother. 18:220, 1980. 52. Cato, E.P., Johnson, J.L.: Reinstatement of species rank for Bacteroides fragilis, B. ovatus, B. distasonis, B. thetaiotaomicron, and B. vulgatus: designation of neotype strains for Bacteroides fragilis (Veillin and Zuber) Castellani and Chalmers and Bacteroides thetaiotaomicron (Distaso) Castellani and Chalmers. Int. J. Syst. Bacteriol. 26:230, 1976. 53. Sperry, J.F., Adamu, S.A.: Polymorphonuclear neutrophil chemotaxis induced and inhibited by Bacteroides spp. Infect. Immun. 33:806, 1981. 54. Brook, I., Finegold, S.M.: Aerobic and anaerobic bacteriology of cutaneous abscesses in children. Pediatrics 67:891, 1981. 55. Brook, I., Randolph, J.: Aerobic and anaerobic flora of burns in children. J. Trauma 21:313, 1981. 56. Brook, I., Finegold, S.M.: The bacteriology and therapy of lung abscess in children. J. Pediatr. 94:10, 1979. 57. Brook, I., et al: Aerobic and anaerobic flora of maternal cervix and newborn’s conjunctiva and gastric fluid: A prospective study. Pediatrics 63:451, 1979. 58. Brook, I., Martin, W.J., Finegold, S.M.: Neonatal pneumonia caused by members of the Bacteroides fragilis group. Clin. Pediatr. 19:541, 1980. 59. Brook, I.: Bacteriology of neonatal omphalitis. J. Infect. 5:127, 1982. 60. Brook, I.: Osteomyelitis and bacteremia caused by Bacteroides fragilis: A complication of fetal monitoring. Clin. Pediatr. 19:639, 1980.

24

Chapter 1

61. Brook, I.: Bacteroides infections in children. J. Med. Microbiol. 43:92.1995. 62. Brook, I., Gillmore, J.D., Coolbaugh, J.C., Walker, R.I.: Pathogenicity of encapsulated Bacteroides melaninogenicus group, Bacteroides oralis, and Bacteroides ruminicola in abscesses in mice. J. Infect. 7:218, 1983. 63. Summanen, P. et al.: Wadsworth Bacteriology Manual, 5th ed. Belmont, CA: Star Publishing, 1993. 64. Brook, I.: Microbiology of human and animal bite wounds. Pediatr. Infect. Dis. J. 6:29, 1987. 65. Brook, I.: Bacteriology of paronychia in children. Am. J. Surg. 141:703, 1981. 66. Brook, I.: Urinary tract infection caused by anaerobic bacteria in children. Urology 16:596, 1980. 67. Brook, I.: Anaerobic osteomyelitis in children. Pediatr. Infect. Dis. J. 5:550, 1986. 68. Slots, J.: The predominant cultivable organisms in juvenile periodontitis. Scand. J. Dent. Res. 85:114, 1977. 69. Brook, I., Grimm, S., Kielich, R.B.: Bacteriology of acute periapical abscess in children. J. Endodontol. 7:378, 1981. 70. Okuda, K., Takazoe, I.: Antiphagocytic effects of the capsular structure of a pathogenic strain of Bacteroides melaninogenicus. Bull. Tokyo Med. Dent. Univ. 14:99, 1973. 71. Brook, I.: Prevotella and Porphyromonas infections in children J. Med. Microbiol. 42:340, 1995. 72. Brook, I.: Fusobacterial infections in children J. Infect. 28:155, 1994. 73. Brook, I., et al: Complications of sinusitis in children. Pediatrics 66:568, 1980. 74. Brook, I., Calhoun, L., Yocum, P.: Beta lactamase producing isolates of Bacteroides species from children. Antimicrob. Agents Chemother. 18:164, 1980. 75. Brook, I.: Infections caused by beta-lactamase-producing Fusobacterium spp. in children. Pediatr. Infect. Dis J. 12:532.1993 76. Brook, I.: Anaerobic and aerobic bacteriology of decubitus ulcers in children. Am. J. Surg. 46:624, 1980. 77. Brook, I., Anthony, B.F., Finegold, S.M.: Aerobic and anaerobic bacteriology of acute otitis media in children. J. Pediatr. 92:13, 1978. 78. Brook, I.: Peptostreptococcal infection in children. Scand. J. Infect. Dis. 26:503,1994. 79. Gossling, J.: Occurrence and pathogenicity of Streptococcus milleri group. Rev. Infect. Dis. 10:257, 1988. 80. Brook, I.: Microaerophilic streptococcal infection in children J. Infect. 28:241, 1994. 81. Brook, I.: Veillonella infections in children. J. Clin. Microbiol. 34:1283, 1996.

2 The Indigenous Microbial Flora in Children

The human body’s mucosal and epithelial surfaces are covered with aerobic and anaerobic micro-organisms.1 The surfaces of the body that are inhabited by normal flora are the skin, conjunctiva, mouth, nose, throat, lower intestinal tract, vagina, and urethra. The organisms that reside at these sites are predominantly anaerobic and are actively multiplying. The trachea, bronchi, esophagus, stomach, and upper urinary tract are not normally colonized by indigenous flora. However, a limited number of transient organisms may by present at these sites from time to time. Differences in the environment, such as oxygen tension and pH and variations in the ability of bacteria to adhere to these surfaces, account for changing patterns of colonization. Microflora also vary in different sites within the body system, as in the oral cavity; for example, the micro-organisms present in the buccal folds vary in their concentration and types of strains from those isolated from the tongue or gingival sulci. However, the organisms that prevail in one body system tend to belong to certain major bacterial species, and their presence in that system is predictable. The relative and total counts of organisms can be affected by various factors, such as age, diet, anatomic variations, illness, hospitalization, and antimicrobial therapy. However, these sets of bacterial flora, with predictable pattern, remain stable through life, despite their subjection to perturbing factors. Anaerobes outnumber aerobic bacteria in all mucosal surfaces, and certain organisms predominate in the different sites (Tables 2.1 and 2.2). The predominance of anaerobic bacteria in the intestinal and genitourinary tracts and their sparsity at other sites is partially due to the differences in oxygen tension at these locations. The number of anaerobes at a site is generally inversely related to the oxygen tension. Their predominance in the skin, mouth, nose, and throat—which are exposed to oxygen—is explained by the anaerobic microenvironment generated by the facultative bacteria that consume oxygen. Knowledge of the composition of the flora at certain sites is useful for predicting which organisms may be involved in an infection adjacent to that site and can assist in the selection of a logical antimicrobial therapy even before the exact microbial etiology of the infection is known. Furthermore, this information can also be helpful in determining the source and significance of microorganisms recovered from unrelated sites of the body. For 25

26

Chapter 2

Table 2.1 Normal Aerobic and Anaerobic Floraa Aerobes

Predominant Anaerobic Organisms

Anaerobes

Skin Oral Cavity

108–9

109–11

Upper GI tract Lower GI Tract Vagina

102–5 105–9 108

103–7 1010–12 109

P. acnes Peptostreptococcus sp. Pigmented Prevotella and Porphyromonas Fusobacterium sp. B. fragilis group Clostridium sp. P. bivia P. disiens

a

Number of organisms per 1 g of secretion or contents.

Table 2.2 Predominant Human Microbial Flora Body Site

Type of Bacteria Aerobic and facultative Staphylococcus sp. Streptococcus sp. Haemophilus sp. Moraxella catarrhalis Enterobacteriaceae Anaerobic Veillonella sp. Peptostreptococcus sp. Actinomyces sp. Bifidobacterium sp. Eubacterium sp. Lactobacillus sp. Propionibacterium sp. Clostridium sp. Fusobacterium sp. Bacteriodes sp. Prevotella sp. Porphyromonas sp. a

Skin

Conjuctiva

Nasopharynx

+ +

+ +

+ +

+

+

Enterococcus sp. Pigmented species c Prevotella bivia and Prevotella disiens. b

+

+

Oral Cavity

+ + +

+ + + + +

+

+ +b +b

+

Lower Gastrointestinal Tract

Genitourinary Tract

+a

+

+

+

+ +

+ + + + + + +

+ + + + + +

+ +c

The Indigenous Microbial Flora in Children

27

example, bacterial endocarditis caused by Enterococcus faecalis is more often associated with urinary tract infection, while endocarditis due to alpha hemolytic streptococci is more often seen in patients with poor dental hygiene and tooth extraction. A knowledge of the indigenous microbiota is also helpful in determining the consequence of overgrowth of one microorganism by another. For example, the overgrowth of Candida within the gastrointestinal tract is frequent in patients given neomycin, because it inhibits the bacteria of the family Enterobacteriaceae but has little effect on Candida. Antimicrobial agents that suppress the intestinal anaerobic bacteria may select for the growth of Clostridium difficile. Uncontrolled proliferation of C. difficile can result in the elaboration of a potent enterotoxin that may cause pseudomembranous enterocolitis. Recognition of the normal flora can also help the clinical microbiology laboratory to choose proper culture media that will be selective in inhibiting certain organisms regarded as contaminants. Furthermore, proper media can be used to enhance the growth of expected pathogens that reside among the indigenous flora near the infection site. The usefulness of such information is apparent during investigation of bacteremia of unknown origin, for which the presence of certain organisms can suggest a possible port of entry (i.e. Clostridium and Bacteroides fragilis usually originate from the gastrointestinal tract).2 The normal flora is not just a potential hazard for the host but also a beneficial partner. An example for such synergy is the development of vitamin K deficiency following antimicrobial therapy, which suppresses the gut flora that produce this vitamin. Normal body flora also serve as protectors from colonization or subsequent invasion by potentially virulent bacteria. In instances where the host defenses are impaired or a breach occurs in the mucous membranes or skin, however, the members of the normal flora can cause infections. THE SKIN The most common members of the cutaneous microflora belong to the bacterial genera Staphylococcus, Micrococcus, Corynebacterium, Propionibacterium, Brevibacterium, and Acinetobacter and the yeast Pityrosporum. (Table 2.2) The indigenous microbiota of the skin will vary greatly depending on the sites of the body and the characteristics of the skin at these sites. The anaerobic propionibacteria, for example, live preferentially in the lipid-secreting glands of the dermis. Most other species are found only on desquamating epithelial cells of the stratum corneum. Organisms such as viruses, which require living cells for hosts, must invade cells of the basal epithelial layers, where there is active cellular metabolism. Some important pathogens commonly found in skin are only transient residents that contaminate the area around orifices. The oral region or sites that can be in contact with the oropharyngeal flora (i.e., nipples, fingers, genitalia) can become colonized with aerobic and anaerobic organisms that originate form the oral flora.3 These organisms include Haemophilus sp., Staphylococcus aureus, Peptostreptococcus sp., Fusobacterium sp., and pigmented Prevotella and Porphyromonas sp. Similarly the rectal, vulvovaginal areas, and lower extremities can become colonized with organisms that originate from the colon and vaginal flora. These include Escherichia coli, Enterococcus sp., B. fragilis groups, Clostridium sp., (in the rectal area) or Neisseria gonorrhoeae, group B Streptococcus, and Prevotella sp. (vaginal origin). Because of this spread, these organisms can cause local in-

28

Chapter 2

fections (wounds, abrasions, infected burns, or decubitus ulcers) or serve as a source of systemic spread or bacteremia.2 The anaerobic microflora of the skin usually is made up of the genus Propionibacterium.4 The majority of the isolates of this genus are Propionibacterium acnes, while Propionibacterium granulosum and Propionibacterium avidum can be recovered less frequently. P. acnes and P. granulosum are found on skin with a high sebum content; P. acnes is found in all postpubertal individuals; whereas P. granulosum is found in 10% to 20% of individuals and then in numbers of about 100 to 1000-fold fewer than P. acnes. The third species, P. avidum, is found in the axillae and seems to need conditions with a high availability of water rather than the presence of abundant lipids. Species of Eubacterium and Peptostreptococcus may also be encountered. These organisms grow within the openings of the sebaceous glands; consequently, their distribution is proportional to the number of glands, the amount of sebum produced, and the composition of skin surface lipids.5 Propionibacterium sp. are capable of producing free fatty acids from triglycerides by generating lipase.6 The degree of hydrolysis of sebum triglycerides varies, but it occurs most effectively with P. acnes and P. granulosum.7 These fatty acids have strong antibacterial and antifungal activity and can interfere with the growth of nonidigenous microorganism on skin surfaces. Staphylococcus sp., Streptococcus pyogenes, and aerobic gram-negative bacilli are sensitive to these fatty acids. The fatty acids generated by Propionibacterium sp. may therefore play a role in excluding more virulent organisms from the skin surfaces thus maintaining the stability of the cutaneous flora. The fatty acids produced by Propionibacterium species may, however, play a deleterious role in the development of acne. These acids, generated in the hair follicles and sebaceous gland ducts, can cause an inflammatory response, resulting in the production of acne lesions.8 In general, the numbers of P. acnes on the skin are higher for adults than for young children. Because of their prevalence in the skin and the ear canal, these organisms can contaminate blood cultures and aspirates of abscesses and inner ear fluid. The occurrence of anaerobic diphtheroids, which were probably P. acnes, was studied by Sommerville and Murphy9 in 22 persons. Considerable variation was noted among the subjects. Sites with mean values of more than 105 anaerobic diphtheroids per centimeter of skin were the forehead, presternal area, subclavicular area, midline upper back, and deltoid area. Sites with the fewest organisms (