Anaerobic Bacteria in Intra-Abdominal Infections and Bacteremia Maria Hedberg, Umeå University, Umeå, Sweden Anaerobic Bacteria: Next Generation Technology Meets Anaerobic Diagnostics ESCMID Postgraduate Technical Workshop September 29 October 1, 2014 Groningen, The Netherlands
SEM of mixed microbial population recovered from the lavage fluid of patient with peritonitis Adapted from Edmiston et al. Clin Infect Dis 2002;35(Suppl 1):S112-118
Intra-abdominal infections (IAI) Occur after entry of enteric microorganisms into the peritoneal cavity through an impairment of the intestinal wall as a result of - obstruction - trauma -surgery Local or generalized peritonitis Abscess formation
IAI Postsurgical intra-abdominal infections Appendicitis Peritonitis Liver abscess Biliary tract infections Retroperitoneal abscess Pelvic abscess
IAI: Location of primary source and 80 70 60 50 40 30 20 10 0 microbiology (Infection 2009; 37:522-527and Drugs 2012; 72:e17-e32) Gastroduodenal Gram-negatives Gram-positives Anaerobes Yeasts Biliary tract Small intestine Primary source of infection Initial culture results in secondary and tertiary peritonitis. Percentages of positive cultures according to the primary source of infection. Colorectal Appendix
Virulence factors of anaerobic bacteria Adhesins Capsule (polysaccharides) Fimbriae Hemagglutinin Lectin Antifagocytic factors Capsule Plasminogen-binding protein IgA, IgM, IgG proteases LPS Volatile fatty acids Resist oxygen toxicity Superoxide dismutase, catalase Tissue destruction Phospholipase C Hemolysins Proteases Collagenase Fibrinolysin Neuraminidase Heparinase Chondroitin sulfatase Glucuronidases N-actylglucosaminidase Volatile fatty acids
Importance of B. fragilis capsule in infection Gastrointestinal lumen Intra-abdominal abscess Blood Capsule + 4 % 79 % 83 % Pili + 81 % 92 % 6 % Adapted from Brook, 1994
Importance of B. fragilis capsule in abscess formation Structures of the B. fragilis polysaccharide repeating units (Tzianabos AO et al., 1993). Comstock LE et al., 1999
Stages of abscess formation Condition Mortality, % Abscess, % Control 37 100 Gentamycin 4 98 Clindamycin 35 5 Clinda/Genta 7 6 Adapted from Bartlett et al., Arch Surg 1978;113:853-857
Retroperitoneal abcesses Bacterial isolate Pancreatic (n=46) Lower GI (n=29) Pelvic retroperitoneal (n=23) Enterococci 11 E. coli 18 19 K. pneumoniae 12 Enterobacteriaceae 4 (other) N. gonorrhoeae 4 AGPC 29 35 V. parvula 6 B. fragilis group 17 20 5 Prevotella sp. 4 5 Numbers of aerobic and anaerobic bacterial isolates from retroperitoneal abscesses in patients treated between 1974 and 1990, n=161 (Brook and Frazier CID 1998; 26:938-941).
Significance of anaerobic bacteria in mixed infections with other flora Encapsulated strains of Bacteroides, Prevotella and Porphyromonas are often more important than aerobic bacteria in the abscess. Encapsulated anaerobic and facultative Grampositive cocci, Clostridium sp. and Fusobacterium sp. are often equal to or less important than their aerobic counterparts, variations exist. As determined by abscess size [in animal model] most of the anaerobic organisms enhanced mixed infections. Brook I. FEMS Microbiol Rev 1994;13:65-74
Synergy between anaerobic and aerobic or Aerobic facultative bacteria facultative anaerobic bacteria Anaerobic Gram-pos. cocci Anaerobic bacteria B. fragilis P. asaccharolytica P. aeruginosa Yes Yes Yes E. coli No Yes Yes K. pneumoniae No Yes Yes P. mirabilis No Yes Yes S. aureus Yes Yes Yes Data from Brook et al. J Infect Dis 1984;149:929-931
Gastrointestinal variant of Lemierre s syndrome (case report) Zheng L, Giri B. Am J Ther 2014 [Epub ahead of print] F. nucleatum linked to to gastrointestinal variant of Lemierre s syndsome Bacteremia and hepatic vein thrombosis Originating from subclinical primary infection in lower GI tract
Treatment of IAI Surgical correction and drainage Administration of antimicrobials effective against aerobic and anaerobic bacteria Geographical and hospital specific differences in susceptibility patterns emphasize the need of individual isolate testing in the case of severe infections involving anaerobes!
Bloodstream infection About 5 % of bacteremia cases involve anaerobic bacteria B. fragilis is the anaerobe most commonly isolated Secondary to infection from the bowel, female genital tract, respiratory tract, oral cavity or soft tissue Transient bacteremia Recovery of anaerobic bacteria from the bloodstream requires anaerobic blood culture bottles!
Risk factors of anaerobic bacteriemia -a case control study (1999-2012) Jpn J Antibiot 2014; 67:133-143 71 patients with anaerobic bacteremia Association between anaerobic bacteremia and malignancy GI and genitourinary tract infections Douglas pouch drains chest drains
Prognostic factors and impact of antibiotherapy in 117 cases of anaerobic bacteremia Eur J Clin Microbiol Infect Dis 2008;27:671 678 Case-control study, France, January 2002- December 2003 to evaluate the impact of bacteremia due to anaerobic bacteria 2 658 /35 922 (7.4 %) positive blood cultures, at least one microorganism. Of these, 184 cultures grew at least one anaerobe bacterium (7 % of positive cultures; 0.5 % of total) 130 anaerobic isolates in total
Prognostic factors and impact of antibiotherapy in 117 cases of anaerobic bacteremia Eur J Clin Microbiol Infect Dis 2008;27:671 678 Anaerobic bacteria most frequently isolated (%) B. fragilis 42 B. fragilis group 20 Clostridium sp. 25 Fusobacterium sp. 12 Anaerobic Gram-positive cocci 9 In 24/117 cases (20 %) also aerobic bacteria were isolated
Prognostic factors and impact of antibiotherapy in 117 cases of anaerobic bacteremia Eur J Clin Microbiol Infect Dis (2008) 27:671 678 Sites of infection in patients with anaerobic bacteremia Origin Number Digestive tract 61 Bone or joint 12 Skin 10 Oropharyngeal 5 Lung or pleura 5 Gynecological 5 Catheter 2 Endocarditis 2 Urinary tract 1 Undetermined 14 Total 117
Prognostic factors and impact of antibiotherapy in 117 cases of anaerobic bacteraemia Eur J Clin Microbiol Infect Dis (2008) 27:671 678 Outcomes 32/117 (27 %) patients died during hospitalization 15/85 (18 %) who received anti-anaerobe drug died 17/29 (59%) who received inactive or poorly active drug died Median length of hospitalization (days): 30 (1-150) Control (days): 18 (2-70)** Median length of ICU stay (days): 28 (2-102) Control (days): 14 (2-43)** **P<0.01
Prognostic factors and impact of antibiotherapy in 117 cases of anaerobic bacteraemia Eur J Clin Microbiol Infect Dis (2008) 27:671 678 Summary Absence of antimicrobial therapy effective against anaerobic bacteria was independently and strongly associated with mortality. Antimicrobial resistance among anaerobes makes the selection of reliable empirical therapy difficult. Isolation of anaerobic bacteria represents a rare but relevant situation in patients with bacteremia that is associated with substantial morbidity and increased length of hospital stay.
Antimicrobial resistance and clinical outcome of Bacteroides bacteremia: findings of a multicenter prospective observational trial Clin Inf Dis 2000;30:870-876 Correlation between in vitro susceptibility testing and clinical response to therapy for Bacteroides bacteremia?
Importance of antimicrobial susceptibility testing! Bacteroides bacteremia: Clinical failures in 20/92 patients Mortality rate in patients who received inactive therapy was higher (45 %) than in patients receiving active therapy (16 %) 5/8 patients who received an antibiotic to which in vitro resistance was noted, died M.H. Nguyen et al. Antimicrobial resistance and clinical outcome of Bacteroides bacteremia: Findings of a multicenter prospective observational trail. 2000; CID 30:870-876.
MDR in B. fragilis in Canada Total 387 isolates 25 % were susceptible to all tested antimicrobial agents 14 % R to 3 agents 8 % 4 2 % 5 0.3 % 6 0.3 % 7 Amox-clav, cefoxitin, clindamycin, imipenem, moxifloxacin, pip-tazo, tigecycline Prevalence of antimicrobial resistance among clinical isolates of B. fragilis group in Canada in 2010-2011: CANWARD surveillance study. Karlowsky JA et al., AAC, 2012
Bloodstream infections (BSI) due to Peptoniphilus spp., case reports 2007-2011 Brown K et al., Clin Microbiol Infect. 2014 [Epub ahead of print] 16S rdna sequencing in patients with pneumonia pre-term-delivery soft tissue infection colon or bladder disease 7/15 polymicrobial BSIs Peptinophilus sp., rare but important cause of BSI
Economic consequences Secondary intra-abdominal infections 16 % failed initial antibiotic therapy Risk of clinical failure 17 % Inappropriate antibiotic treatment increased risk of clinical failure 3-fold Hospitalization prolonged about 7 days Costs incurred 6,300 Sturkenboom M et al., Br J Clin Pharmacol, 2005 Complicated intra-abdominal infections 22 % failed initial antibiotic therapy Hospitalization prolonged about 5 days About 4 % higher risk to die in the hospital Costs incurred 6,400$ Edelsberg J et al., Surg Infect, 2008
Conclusion Proper treatment of sever anaerobic infections will save lives, costs and pain
Thank you for your attention!