Lege Artis Medicinae

[The microbiology pharmacokinetics and clinical use of carbapenems]

BÁN Éva1, PRINZ Gyula2

MARCH 01, 2000

Lege Artis Medicinae - 2000;10(03)

[ Imipenem and meropenem the two currently available carbapenems inhibit the synthesis of the cell wall similarly to other bactericidal B-lactam antimicrobials. These agents have excellent activity against the vast majority of aerobic and anaerobic Gram-positive and Gram-negative organisms. In addition to other B-lactam resistant microbes (e.g. Chlamydia, Mycoplasma) only Stenotrophomonas maltophilia and Enterococcus faecium bacteria are naturally resistant to carbapenems. Carbapenems are extremely stable compounds against nearly all types of B-lactamases: from the penicillinase of Staphylococcus to Class A and Class B types of B-lactamase enzymes of Gram-negative bacteria. Secondary resistance against carbapenems was described in case of the following bacteria: penicilline resistant S. pneumoniae, methicilline resistant Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter cloaceae, less frequently Enterobacter aerogenes, Serratia mercescens, Klebsiella pneumoniae and Acinetobacter baumannii. The pharmacokinetic profile of imipenem and meropenem are very similar. Carbapenems are valuable as empirical monotherapy due to their broad spectrum of antimicrobial activity and ß lactamase stability in the treatment of severe nosocomial infections, lower respiratory tract or intraabdominal infections and febrile neutropenia. The use of imipenem in central nervous system infection is not approved due to the high incidence of seizures. ]


  1. Mikrobiológiaia Laboratórium, Fővárosi Szent László Kórház, Budapest
  2. IV. Belgyógyászati Osztály, Fővárosi Szent László Kórház, Budapest



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Lege Artis Medicinae

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Lege Artis Medicinae

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Lege Artis Medicinae


KONKOLY Thege Marianne, BÁN Éva, LUDWIG Endre

[INTRODUCTION - The clinical significance of Gram-negative infections has not diminished in recent years. The number of resistant and multiresistant isolates has increased among Gramnegatives similarly to Gram-positive bacteria. Moreover, panresistant strains (i.e. resistant to all available agents active against Gram-negatives) have emerged. A prospective, multicenter study carried out in 2000 was repeated in 2004 in order to have up to date knowledge of resistance situation of Gram-negative aerobic bacteria and Bacteroides fragilis. In addition, the local data of 2004 were compared to MYSTIC (Meropenem Yearly Susceptibility Test Information) database of year 2004. MATERIALS AND METHODS - The in vitro study protocol-guided was carried out in 20 microbiology laboratories from April 1 to November 15, 2004. Study strains were isolated from relevant samples taken in medical, surgical, haematology, infectious disease wards and intensive care units. The sensitivity of 2099 aerobic Gram-negative and 97 B. fragilis isolates to meropenem and its comparator agents with excellent Gram-negative and/or antianaerob activity was tested according to NCCLS (National Committee for Clinical Laboratory Standards). RESULTS - Meropenem and imipenem have almost retained their 100% activity against Enterobacteriaceae, Acinetobacter and B. fragilis. A very small number of carbapenem nonsusceptible isolates emerged among Enterobacter, Proteus and Acinetobacter strains. Meropenem and especially imipenem sensitivity of Pseudomonas aeruginosa decreased significantly over the 4-year interval (76% vs 67%). The difference between the meropenem and imipenem sensitivity of P. aeruginosa proved significant (<0.001) and a similar difference was found in MYSTIC Programme. The isolation frequency of extended spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella strains was relatively low (4.1% and 8.5%, respectively) in Hungary comparing to that in other European countries. Only the carbapenems inhibited consistently the ESBLproducing strains whereas ceftazidime, cefepime and piperacillin/tazobactam were ineffective versus these strains. The rate of cefepime sensitive strains declined significantly in case of Enterobacter (82%), Citrobacter (90%), Acinetobacter (31%) and P. aeruginosa (69%), whereas it did not change among Serratia and Proteus strains. The activity of ceftazidim has decreased, as well: 61% of Enterobacter, 74% of Citrobacter, 15% of Acinetobacter and 78% of P. aeuginosa isolates were sensitive to it. A trend over time toward greater resistance was noted for piperacillin/tazobactam, however, it remained the most active in vitro agent against P. aeruginosa (83%). This rate is better than that was found in MYSTIC. There was not a clear trend in changes of sensitivity to aminoglycosides in Gram-negatives. A significant decrease in gentamicin and tobramycin sensitivity of E. coli and Klebsiella was noted (<90%), and in gentamicin, tobramycin and amikacin sensitivity of P. aeruginosa (57%, 65%, and 79%, respectively). Ciprofloxacin sensitivity also declined over the years: E. coli 85%, Proteus 83%, Acinetobacter 16%, P. aeruginosa 68%. Aztreonam and polymyxin sensitivity were examined only in case of P. aeruginosa because these two agents may be the drugs of choice in infections caused by multior panresistant strains: all isolates were susceptible to polymyxin, and 84% of them to aztreonam. However, panresistant isolates were not sensitive to aztreonam. Ampicillin/sulbactam may be a possible alternative drug in serious infections caused by multiresistant Acinetobacter: 83% of isolates showed sensitivity to it. Carbapenems, piperacillin/tazobactam and metronidazole were active against B. fragilis in 100%, amoxicillin/clavulanic acid resistance occurred scarcely, whereas clindamycin sensitivity was only 79%. CONCLUSIONS - There is no single antibacterial agent which would be effective against >90% of most frequently occurring Gram-negative aerobic bacteria in Hungary. The high increase in resistance rates over a relatively short 4-year period will result in serious challenges in the therapy. At the same time the Hungarian sensitivity rates are better than those reported by MYSTIC Programme.]