Increasing numbers of infections caused by antibiotic-resistant gram-positive organisms such as S aureus, group A streptococci (GAS), and Streptococcus pneumoniae are being recognized in both children and adults. Understanding the types of drug resistance that exist is crucial to clinicians' selection of therapeutic approach. Robert Daum, MD, of the University of Chicago reported on a new, lethal syndrome of S aureus sepsis in nonhospitalized infants and young children. Affected patients exhibit hypotension and shock, necrotizing pneumonia, coagulopathy, and thrombocytopenia, and are often first thought to have meningococcal sepsis. Both methicillin-sensitive and methicillin-resistant S aureus (MRSA) have been causally associated with this syndrome, part of which may be due to the Panton Valentin leukocidin exotoxin that such organisms can produce and which is responsible for tissue necrosis.
Dr. Daum addressed the question of how to treat children who present with this S aureus-associated syndrome. Community-acquired MRSA isolates often test as susceptible to clindamycin, in contrast to hospital-acquired MRSA. Some clinical studies have suggested that this drug is usually clinically effective, but Dr. Daum was not completely convinced. Many clinical laboratories are now performing a "D" test to determine whether erythromycin-inducible resistance to clindamycin is present in MRSA. Unfortunately, the clinical significance of this indicator is not yet clear: Some patients appear to respond to clindamycin despite a positive D test, while others do not.Macrolide Resistance in Group A Streptococci (GAS)
Michael Green, MD, of the Children's Hospital of Pittsburgh reported on macrolide resistance in GAS, which is mediated by both methylation of the 50S ribosome and an efflux pump. Resistance is both constitutive and inducible. Macrolide-resistant GAS was first reported in Great Britain in the 1950s and was noted to be common in Europe in 1968. It is still uncommon in the United States, but its incidence is variable from place to place. In Pittsburgh, for example, 48% of GAS isolates were found to be resistant to macrolide drugs. By contrast, Tanz and associates found that only 4% of US GAS isolates were resistant. Dr. Green and colleagues reported similar rates of resistance in a recent national survey of GAS isolates. These latter data are somewhat reassuring, but further vigilance is required. The main concern is that persons at high risk for rheumatic fever who have pharyngeal infections caused by macrolide-resistant GAS will not receive optimal therapy; clinicians therefore need to be aware of the potential problem and its extent as suggested by surveillance studies.Resistance in Pneumococci
Sheldon Kaplan, MD, of Baylor College of Medicine discussed the fact that pneumococcus remains an important pediatric pathogen, even with the widespread implementation of the conjugated pneumococcal vaccine. Increasing resistance among pneumococci has been reported since 1988. In addition to resistance to penicillin, pneumococci are often resistant to other antibiotics. Currently, an estimated 20% of isolates are resistant to erythromycin, clindamycin, and trimethoprim sulfa. For children with suspected pneumococcal meningitis, treatment with cefotaxime or ceftriaxone and vancomycin therefore remains standard. For penicillin-allergic children, vancomycin and rifampin are used. However, for organisms that are highly resistant to cefotaxime or ceftriaxone (MIC ≤ 4 mcg/mL), meropenem may be tried, although there are not many data to support this. Data regarding treatment with quinolones are even more scant.
For children with nonmeningeal but severe systemic pneumococcal infections due to resistant organisms, the Red Book does NOT recommend the use of macrolides, although it does suggest that clindamycin might be used. Currently, less than 50% of pneumococci causing otitis media are susceptible to macrolides. It is thought that the efflux mechanism is responsible for most of this resistance. High-dose amoxicillin (80 mg/kg/day) for 10 days may be used as an approach to decrease carriage of these organisms. The recent decline in otitis media infections caused by penicillin-resistant organisms, which has been attributed to vaccine effects, may ameliorate this situation, however.Extended-Spectrum Beta-Lactamases
Jan Patterson, MD, of the University of Texas Health Science Center reviewed how bacteria become resistant to antimicrobials, citing changes in porins in gram-negative organisms, alteration of penicillin-binding proteins in gram-positive organisms, as well as ribosomal and efflux mechanisms of resistance. She devoted further discussion to beta-lactamases, of which there are now over 100. Beta-lactamases are variably inhibited by clavulanate: group 1 beta-lactamases are not inhibited by clavulanate and are produced by many hospital-acquired organisms; group 2 beta-lactamases are inhibited by clavulanate. Extended-spectrum beta-lactamases (ESBLs) are included in Group 2-b ESBLs, which are largely associated with Klebsiella pneumoniae, were first described in Europe in 1983, and were recognized in the United States in the late 1980s. In the United States, ESBLs are rarely produced by Escherichia coli. In certain organisms, production of ESBLs may not occur at standard drug dilutions, but at higher inocula, their production becomes apparent. ESBL production also seems to correlate with severe infections. Fortunately, with decreasing use of third-generation cephalosporins, the incidence of ESBL-producing organisms may be decreasing in the United States. Recommendations for control of ESBLs include: control of ceftazidime and cefotaxime use; controlled use of piperacillin/tazobactam for serious infections; controlled use of imipenem for resistant, gram-negative infections; employment of infection-control precautions for patients infected with organisms that produce ESBLs; education of medical and nursing personnel about ESBLs; and screening for ESBLs by clinical laboratories with rapid testing.References
Daum RS. Community-acquired MRSA. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 426.
Mongkolrattanothai K, Boyle S, Kahana MD and Daum RS. Severe Staphylococcus aureus infections caused by clonally related community-acquired methicillin-susceptible and methicillin-resistant isolates. Clin Infect Dis. 2003;37:1050-1058.
Green MD. Macrolide resistance in group A streptococcus. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 427.
Martin JM, Green M, Barbadora KA, Wald ER. Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh. N Engl J Med. 2002;346:1200-1206.
Tanz RR, Shulman ST, Kabat W, et al. Differences in macrolide resistance rates among pharyngeal group A streptococci in the U.S. and Canada. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 209.
Green M, Allen C, Bradley J, et al. Macrolide resistance among pharyngeal isolates of group A streptococci (GAS) in the USA: multicenter surveillance study (2002-2003). Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 210.
Kaplan SL. Pneumococcus. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 428.
Schrag SJ, Pena C, Fernandez J, et al. Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: a randomized trial. JAMA. 2001;286:49-56.
Patterson JE. Extended spectrum beta-lactamases. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 429.
Rahal JJ, Urban C, Horn D, et al. Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. JAMA. 1998;280:1233-1237.
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Cite this: Anne A. Gershon. Antimicrobial Resistance in Community-Acquired Pediatric Infections - Medscape - Nov 05, 2003.