Lege Artis Medicinae

[Microbiology - contagious thoughts]

BARCS István

JUNE 20, 2013

Lege Artis Medicinae - 2013;23(05-06)

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Lege Artis Medicinae

[Optimizing the efficacy of triple combination therapy of chronic hepatitis C]

TORNAI István

[The outcome of chronic hepatitis C (CHC) therapy has been improved significantly. If sustained virologic response (SVR) is achieved, then it may prevent the occurrence of liver failure and hepatocellular carcinoma. With the currently used double combination therapy (peginterferon and ribavirin) SVR can be achieved in 40-50% of patients with genotype 1. In treatment naive patients, triple combination with protease inhibitors can result in 70-75% SVR. In treatment experienced patients, however, the result of the previous therapy, which mostly depends on the reaction to interferon (IFN), has a significant influence on the outcome of triple combination. INF sensitivity is the highest in relapsers, triple combination can achieve about 85% SVR, while in null responders this is only 30%. Viral resistance is a new phenomenon during triple combination therapy of CHC. In poorly IFN responsive patients the virus is effectively exposed to protease inhibitor functional monotherapy, leading to the rapid emergence of resistant virus. IFN sensitivity is well represented by the on-treatment viral response, therefore the knowledge of the previous viral response, relapse, a partial response or a null response is absolutely important. Optimization of triple therapy is crucial, since for a lot of patients with advanced liver disease it might be the last chance to achieve an SVR. The selection of the patients seems very important. Relapsers are the best candidates, there is no doubt with the indication. However, there are many debates for cirrhotic nullresponders, since the most virological failures are expected in this group. Prevention of viral resistance is crucial. PegIFN and ribavirin suppress both wild-type and resistant virus. PegIFN α-2a based treatment proved to be the most effective backbone for triple combination. This combination should be preferred especially for treatment experienced patients. Adherence to therapy is also critically important to prevent resistance. If resistant mutants appear, treatment should be stopped promptly.]

Lege Artis Medicinae

[A Teacher who Created a School ]

BEDROS J. Róbert

Lege Artis Medicinae

[Development of the diagnostic criteria of Alzheimer’s disease]

KOVÁCS Tibor

[Alzheimer’s disease is a new endemic of the 21st century, which is going to become the biggest health and social problem of the ageing societies in the next few decades. Significant discoveries have been made by structural and functional imaging and biochemical (especially CSF) and genetic tests regarding the diagnosis of Alzheimer’s disease. The modern diagnostic results were recently incorporated into the diagnostic criteria. This review summarises these diagnostic results.]

Lege Artis Medicinae

[Summer Exhibitions at the Museum of Fine Arts ]

NAGY Zsuzsanna

Lege Artis Medicinae

[The EDUVITAL concept: self-conscious epigenetics for our health]

FALUS ANDRÁS, MELICHER Dóra

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[CHANGES IN SENSITIVITY OF NOSOCOMIAL GRAM-NEGATIVE PATHOGENS TO MEROPENEM AND ITS COMPARATIVE AGENTS DURING A FOUR-YEAR PERIOD (2000-2004) - ANALYSIS OF DATA FROM TWO PROSPECTIVE MULTICENTER STUDIES IN HUNGARY]

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.]