Lege Artis Medicinae

[IN VITRO SENSITIVITY OF PSEUDOMONAS AERUGINOSA STRAINS AND ITS CLINICAL CONSEQUENCES IN HUNGARY]

LUDWIG Endre, KONKOLY Thege Marianne

NOVEMBER 30, 2004

Lege Artis Medicinae - 2005;15(03 klsz)

[INTRODUCTION - The antibiotic sensitivity of Pseudomonas aeruginosa isolates in nosocomial infections was determined in a prospective multicenter study in Hungary. METHODS - The sensitivity of 441 nonduplicated Pseudomonas aeruginosa isolates were determined by E-test methodology. Antibiotic sensitivities were determined according to the NCCLS standard. RESULTS - The sensitivity of isolates decreased compared to the results of 2000 surveillance data (meropenem 83 vs 76%, imipenem 82 vs 67%, ceftazidime 80,2 vs 78%, piperacillin/tazobactam 86.3 vs 83%, amikacin 88.2 vs 79%, ciprofloxacin 75,9 vs 68%). The highest resistance rates were detected at the intensive care units and in case of isolates from bloodstream infections. CONCLUSIONS - The antibiotic sensitivity of Pseudomonas aeruginosa isolates decreased in the last three years and the high resistance rates detected in intensive care units and of invasive strains are of special concern. For effective therapy antibiotics should be used in high doses and betalactams given in prolonged infusions might be more efficacious than administered in bolus. In case of probable Pseudomonas infections the use of two effective antipseudomonas agents is recommended. Prudent use of the antibiotics and effective infection control are needed to prevent the further loss of activity of these antimicrobial agents.]

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Lege Artis Medicinae

[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

[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.]

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Lege Artis Medicinae

[In vitro sensitivity of human anaerobic pathogenic bacteria for tigecycline and comparative antibiotics in Hungary - Prospective multicentre trial]

NAGY Erzsébet, URBÁN Edit, JAKAB Gabriella, SZIKRA Lenke, MISZTI Cecília, SZABÓ Judit

[INTRODUCTION - Tigecycline, the first member of the glycylcycline family of antibiotics, is a semisynthetic derivative of minocycline. The modified tetracycline nucleus is protected against the resistance mechanisms that inactivate tetracyclines, thus tigecycline is expected to be effective against tetracycline- resistant strains. The aim of this multicenter survey, performed in 2007 and 2008 by three Hungarian laboratories, was to examine the efficiency of this drug against antianaerobic bacteria in vitro. MATERIALS AND METHODS - The participating laboratories isolated 540 strains of Gram-positive and Gram-negative anaerobic bacteria from various infectious sites. These sites represent the classes of infections for which tigecycline was recently approved as a treatment option (skin and soft tissue and intra-abdominalinfections), or for which it will be licensed in the near future (lower respiratory tract infections). Evaluation of antibiotic susceptibility was performed by Etest, and the efficiencies of six antibiotics were determined using MIC values. RESULTS - The 540 strains belonged to 33 different species. Of the 104 strains of Gram-positive anaerobic cocci, 100% proved to be susceptible to tigecycline. Similarly, 98% of the examined Clostridium strains showed susceptibility to this antibiotic. Two of the 56 Prevotella strains were resistant against tigecycline. MIC50 and MIC90 values in the 280 Bacteroides strains were 0.5 μg/ml and 1 μg/ml, respectively, whereas only 1.8% of the tested strains showed low resistance. CONCLUSION - Similarly to the findings of international surveys, our results show that tigecycline is effective against the great majority (97.4% susceptibility) of relevant anaerobic bacteria that are isolated from skin and soft tissue, intra-abdominal and lower respiratory tract infections. Thus, empiric use of tigecycline is recommended in any infections where anaerobic bacteria alone or a mixed flora of aerobic and anaerobic bacteria are likely to be present.]

Lege Artis Medicinae

[Treatment of chronic Pseudomonas aeruginosa lung infections in cystic fibrosis with inhaled tobramycin]

NAGY Béla, HOLICS Klára

[BACKGROUND - Intermittent or chronic pulmonary infections caused by Pseudo­monas aeruginosa (Pa) deteriorate clinical status and worsen lung function in patients with cystic fibrosis (CF). The prognosis of the disease and life expectancy of patients are substantially dependent on lung infections and inflammation; therefore the primary goal of the treatment is the early termination of the infection. PATIENTS AND METHODS - Efficacy of tobramycin (TOBI® 300 mg/5 mL solution for inhalation, henceforth TOBI®) inhalation in Pa pulmonary infections was studied in a non-interventional, observational, open-label, single-arm trial in subjects with CF. Fifty-three patients aged six to 31 years (averaged 15.8 years) were enrolled into the study. Three treatment cycles of TOBI® inhalation (28 days on drug, 28 days off drug) plus 6 months observational period were evaluated. Primary endpoint was changing in the predictive values of forced expiratory volume in 1 sec (FEV1) compared to the initial values after three cycles of the treatment. Secondary endpoints were changing in the FEV1 predictive values at the end of the complete study compared to the initial values; ratios of patients with decreased density of originally Pa-positive result of sputum culture; as well as safety and tolerability of the TOBI® treatment. RESULTS - FEV1 and FEV1% results were unchanged comparing to the initial values at the end of the treatment and after the observational period in the whole study population. However, sputum cultures became negative in 47.2% of all subjects as a result of the treatment, and the FEV1 values were gradually increased in these patients: after the third treatment cycle plus 160 mL, and at the end of the study plus 110 mL comparing to the initial values. Similar considerable increase was detected in the predictive FEV1% in this sub-group: after the first cycle plus 5.2%, at the end of third cycle plus 7%, after the observational period above 3.8% considering the starting results. CONCLUSIONS - TOBI® inhalation proved to be effective in improvement of lung function results and eradication of infection in our patients with Pa positive CF. The treatment was well tolerated and safe.]

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[About the care of patients with hyperuricaemia and gout]

[This consensus document is intended to provide guidance for the effective and efficient treatment of asymptomatic individuals with high uric acid levels and gout patients.]