ESBLs

Class A Serine p-lactamases SHV-1 penicillinase in K. pneumoniae, and Koxy with activity against certain third generation cephalosporins in K. oxytoca BlaZ staphylococcal penicillinase TEM, SHV, VEB, PER and CTX-M penicillinases and ESBLs (P-lactamases with activity against third generation cephalosporins and aztreo-nam) KPC, IMI/NMC and SME carbapenemases... 

Local treatment of skin and soft tissue infections with antibiotic-containing ointments or solutions should not be used because it leads to allergic reactions and rapid development of bacterial resistance. In settings where MRSA or resistant Enterobacte-riaceae (like ESBL s gram negative bacteria with extended spectrum beta lactames) or Pseudomonas spp. occur, the empiric use of vancomycin and a carbapenem can be necessary. The risk of transmission of these organisms should be minimalised by hygienic and isolation measures. 

Meropenem (Merrem) is another carbapenem antibiotic with a broad spectrum of activity comparable to that of imipenem. A methyl group attached at the one-position on the five-member ring confers stability to dehydropeptidase 1. Consequently, meropenem does not require administration with cilastatin. When compared in human trials, imipenem-cilastatin and meropenem achieve similar clinical outcomes in patients with serious intraabdominal and soft tissue infections. Both imipenem-cilastatin and meropenem are used to treat infections caused by highly resistant Klebsiella pneumoniae producing ESBLs.The major cUnicaUy relevant distinction between imipenem-cilastatin and meropenem... 

The importance to the continuing study of the molecular mechanism of the /3-lactamases, for the purpose of assessing new /3-lactam structure and for the conceptual development of ideas to preserve the clinical efficacy of the /3-lactams, is certain. Two recent observations underscore this assertion. The basis for /3-lactam resistance by Mycobacterium tuberculosis is the possession of a chromosomally encoded Class A ESBL /3-lactamase, BlaC. This /3-lactamase is, however, inactivated by clavulanate, suggesting the utility of combination /3-lactam-clavulanate therapy for tuberculosis. " A second example involves the site-directed mutagenesis... 

ESBL extended spectrum /3-lactamase MRSA methicillin-resistant Staphylococcus aureus PBP penicillin binding protein... 

B. subtilis, S. aureus, methicillin-resistant coagulase-negative staphylococci, vancomycin-resistant Enterococcus faecium, ESBL-positive K. pneumonia, S. typhi. Vibrio choiera... 

D.L. Paterson, W.C. Ko and S. Mohapatra et al. Klebsiella pneumoniae bacteremia impact of extended spectrum beta-lactamase (ESBL) production in a global study of 216 patients (abstract). 37 Interscience Conference on Antimicrobial Agents and Chemotherapy Sept. 28-Oct. 1 Toronto, Ontario, Canada, 1997. 

The concentration of meropenem in breast milk was evaluated in a study of a 41-year-old woman treated for a postpartum urinary tract infection caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli with meropenem 1 g IV q 8 h. Levels were taken from five samples, and ranged from 0.246 mcg/mL to 0.644 mcg/mL. The average breast milk concentration was 0.48 mcg/mL. It was found that the levels were comparable to those of imipenem in breast milk [75 ]. 

An 84-year-old woman was treated with ertapenem 1 g IV daily for an ESBL E. coli UTl. Her CrCl was 37 mL/ min (by Cockgroft-Gault) on admission. Although her UTl symptoms improved, she became confused, disoriented and experienced visual hallucinations. MRI, GSF examination, chest X-ray and cultures did not reveal any causative reason for her disorientation. Due to the timing of onset and rule-out of other potential causes, ertapenem was discontinued and quetiapine was initiated for delirium. She returned to her baseline mental status 2 weeks later. The authors speculate that this patient was at higher risk of these effects from ertapenem because she had history of brain infarction. This case brings attention to the potential risk of prolonged encephalopathy related to ertapenem [80 ]. 

Abbreviations. MDR, multidrug resistant ESBL, extended spectrum P-lactamases MSSA, methicillin-sensitive Staphylococcus aureus, MRSA, methicillin-resistant Staphylococcus aureus. 

Of more clinical significance are the producers of ESBLs, which result... 

The ability to detect ESBLs has clinical relevance because it will have an impact on antibiotic therapy. Producers of ESBLs are suspected when susceptibility testing indicates resistance to ceftazidime (but may be paradoxically susceptible to ceftriaxone and cefotaxime by the minimal inhibitory concentration [MIC] or disc diffusion) and susceptible to the cephamycins (11). More recently, a breakpoint of 2 ig/mL to cefpodoxime has been suggested as a standard. Another method of detection is the use of the E-test strip with a gradient of ceftazidime on one side and ceftazidime in combination with clavu-lanate on the other. The ESBLs are thought to be present when enhancement of inhibition is demonstrated. Table 2 highlights some of the more common resistance mechanisms for antimicrobial agents used commonly in the treatment of nosocomial pneumonia. 

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