Ertapenem versus cefepime for initial empirical treatment of pneumonia acquired in skilled-care facilities or in hospitals outside the intensive care unit.

The study presented here compared the efficacy and safety of ertapenem and cefepime as initial treatment for adults with pneumonia acquired in skilled-care facilities or in hospital environments outside the intensive care unit (ICU). Non-ventilated patients developing pneumonia in hospital environments outside the ICU, in nursing homes, or in other skilled-care facilities were enrolled in this double-blind non-inferiority study, stratified by APACHE II score (15) and randomized (1:1) to receive cefepime (2 g every 12 h with optional metronidazole 500 mg every 12 h) or ertapenem (1 g daily). After 3 days of parenteral therapy, participants demonstrating clinical improvement could be switched to oral ciprofloxacin or another appropriate oral agent. Probable pathogens were identified in 162 (53.5%) of the 303 randomized participants. The most common pathogens were Enterobacteriaceae, Streptococcus pneumoniae, and Staphylococcus aureus, isolated from 59 (19.5%), 39 (12.9%), and 35 (11.6%) participants, respectively. At the test-of-cure assessment 7-14 days after completion of all study therapy, pneumonia had resolved or substantially improved in 89 (87.3%) of 102 clinically evaluable ertapenem recipients and 80 (86%) of 93 clinically evaluable cefepime recipients (95% confidence interval for the difference, -9.4 to 11.8%), fulfilling pre-specified criteria for statistical non-inferiority. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this study population, ertapenem was as well-tolerated and efficacious as cefepime for the initial treatment of pneumonia acquired in skilled-care facilities or in hospital environments outside the ICU.

Antimicrobial resistance of nasopharyngeal pneumococci from children from day-care centres and orphanages in Russia: results of a unique prospective multicentre study.

This study assessed the antimicrobial resistance of nasopharyngeal pneumococci isolated from children aged < 5 years in day-care centres and orphanages throughout Russia during 2001-2002. Swabs were collected from 2484 children in 43 day-care centres and eight orphanages in 11 cities of European Russia, and from 1669 children in 37 day-care centres and three orphanages in eight cities of Asian Russia, with a total of 1144 and 912 Streptococcus pneumoniae isolates being recovered in European and Asian Russia, respectively. All macrolide-non-susceptible (MICs 0.5-128 mg/L) and fluoroquinolone-non-susceptible (ciprofloxacin MICs > or = 4 mg/L) isolates were tested for resistance mechanisms and clonal relatedness. Non-susceptibility rates, by CLSI criteria, were 19.3%, 0.9% and 0.4% for penicillin G, cefotaxime and amoxycillin-clavulanate, respectively. Resistance to macrolides and lincosamides was also relatively low, i.e., < 7% for clindamycin and 14- and 15-membered macrolides. The highest rates of non-susceptibility were for tetracycline and co-trimoxazole (52.0% and 64.5%, respectively). No clones resistant to ciprofloxacin (MICs > or = 8 mg/L) were found, but 1.7% of isolates were non-susceptible (MIC 4 mg/L). No resistance was found to levofloxacin, gemifloxacin, telithromycin or vancomycin. Pulsed-field gel electrophoresis analysis showed no relationship between ciprofloxacin- and macrolide-non-susceptible isolates in European and Asian Russia. Resistance among macrolide-resistant isolates resulted mostly from the presence of erm(B) and mef(A), and from changes in L4; additionally, L22 mutations were common in isolates from Asian Russia. Non-susceptibility to quinolones was associated with mutations in parC and parE among European isolates. Asian Russian isolates had mutations in parC and gyrA, and alterations in parE were more common. There were substantial differences in non-susceptibility and mechanisms of resistance between pneumococci from Asian and European Russia, with orphanages appearing to be 'hot-spots' of resistance.

Antimicrobial resistance of nosocomial strains of Staphylococcus aureus in Russia: results of a prospective study.

A total of 879 Staphylococcus aureus clinical isolates from 17 medical institutions in different regions of Russia were tested. Susceptibility to 18 antimicrobials was determined by agar dilution in accordance with the NCCLS recommendations. The most potent antimicrobials were glycopeptides, linezolid, and fusidic acid, to which no resistance was found. Other antimicrobials with low frequency of non-susceptibility were mupirocin (0.3%), trimethoprim/sulfamethoxazole (0.8%), quinupristin/dalfopristin (1.8%) and rifampicin (7.0%). Fluoroquinolones displayed moderate activity (5.8% of non-susceptible strains to moxifloxacin, 9.1% to levofloxacin, 13.1% to ciprofloxacin). High rates of non-susceptibility were found to clindamycin (27.1%), gentamicin (30.7%), tetracycline (37.1%), erythromycin (39.6%) and chloramphenicol (43.1%). The prevalence of oxacillin-resistant S. aureus (ORSA) was 33.5% and varied from 0% to 89.5% in different hospitals. ORSA were isolated most frequently in the burn units (77.5%), intensive care units (54.8%), trauma and orthopedics units (42.1%). This is the first multicenter study published of antimicrobial resistance of S. aureus in Russia which meets international standards.

Multiple outbreaks of nosocomial salmonellosis in Russia and Belarus caused by a single clone of Salmonella enterica serovar Typhimurium producing an extended-spectrum beta-lactamase.

Thirty-four cefotaxime-resistant Salmonella enterica serovar Typhimurium isolates representative of the isolates that caused outbreaks of gastroenteritis in 10 hospitals in seven regions of Russia and Belarus from 1994 to 2003 were analyzed. All isolates produced the CTX-M-5-like extended-spectrum beta-lactamase, which confers high-level resistance to cefotaxime and ceftriaxone and decreased susceptibility to ceftazidime. The bla(CTX-M) genes were located on small (7.4- to 12-kb) non-self-transferable plasmids approximately 20 bp downstream of the ISEcp1 insertion sequences. Some isolates carried additional conjugative plasmids mediating resistance to penicillin-inhibitor combinations and various non-beta-lactam agents, including tetracycline, chloramphenicol, gentamicin, tobramycin, and co-trimoxazole. Despite the minor differences in susceptibility patterns, all isolates were considered clonally related on the basis of arbitrarily primed PCR and pulsed-field gel electrophoresis analysis. The similarities of the restriction profiles of the CTX-M-coding plasmids further supported the clonal origin of these isolates.

Use of quantitative and objective enzyme immunoassays to investigate the possible association between Chlamydia pneumoniae and Mycoplasma pneumoniae antibodies and asthma.

Sera from 150 consecutive patients with established asthma and 150 matched controls were examined for Chlamydia pneumoniae IgG and IgA with commercially available enzyme immunoassays (EIAs) detecting immune response solely to surface proteins of elementary bodies. The assays were also modified to measure combined immune response to surface proteins and family-specific lipopolysaccharide antigen. Mycoplasma pneumoniae IgG and IgA were measured with new commercial EIAs utilising P1-enriched protein fraction as an antigen. No statistically significant differences between the patient groups in terms of prevalence or levels of antibodies to either organism were found with these methods.

European recommendations for antimicrobial resistance surveillance.

The problem of antimicrobial resistance surveillance in Europe has been debated extensively in many excellent documents issued by national committees that often assume the value of national guidelines. However, a comprehensive document addressing the whole matter from a European perspective, as well as reviewing its present status and drafting future perspectives, has been lacking. The present recommendations have been produced by the ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS) through a consensus process involving all members of the Study Group. The recommendations focus on the detection of bacterial resistance and its reporting to clinicians, public health officers and a wider-and ever-increasing-audience. The leading concept is that the basis for resistance monitoring is microbiological diagnostics. The prerequisites for resistance monitoring are findings of adequate quality and quantity, which have been recorded properly and evaluated correctly. Different types of surveillance studies should fulfil different requirements with regard to data collection and reporting, the expected use of data, and the prerequisites for networking such activities. To generate relevant indicators, bacterial resistance data should be reported using adequate denominators and stratification. Reporting of antimicrobial resistance data is necessary for selection of empirical therapy at the local level, for assessing the scale of the resistance problem at the local, national or international levels, for monitoring changes in resistance rates, and for detecting the emergence and spread of new resistances types. Any type of surveillance study should conclude, where appropriate, with a proposal for intervention based on the data obtained.

Prevalence and molecular epidemiology of CTX-M extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Russian hospitals.

A total of 904 consecutive nosocomial isolates of Escherichia coli and Klebsiella pneumoniae collected from 28 Russian hospitals were screened for production of extended-spectrum beta-lactamases (ESBLs). The ESBL phenotype was detected in 78 (15.8%) E. coli and 248 (60.8%) K. pneumoniae isolates. One hundred fifteen isolates carried the genes for CTX-M-type beta-lactamases, which, as shown by PCR-restriction fragment length polymorphism analysis, were distributed into the two genetic groups of CTX-M-1 (93%)- and CTX-M-2 (7%)-related enzymes. Isolates producing the enzymes of the first group were found in 20 hospitals from geographically distant regions of the country and were characterized by considerable diversity of genetic types, as was demonstrated by enterobacterial repetitive consensus PCR typing. Within this group the CTX-M-3 and the CTX-M-15 beta-lactamases were identified. In contrast, the enzymes of the CTX-M-2 group (namely, CTX-M-5) were detected only in eight clonally related E. coli isolates from a single hospital. Notably, the levels of resistance to ceftazidime were remarkably variable among the CTX-M producers. This study provides further evidence of the global dissemination of CTX-M type ESBLs and emphasizes the need for their epidemiological monitoring.

Cefepime versus imipenem-cilastatin for treatment of nosocomial pneumonia in intensive care unit patients: a multicenter, evaluator-blind, prospective, randomized study.

In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (-16 to 8%) failed to exclude the predefined lower limit for noninferiority of -15%. In addition, therapy of pneumonia caused by an organism producing an extended-spectrum beta-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, -9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P = 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, -23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P = 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P = 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological efficacies. Cefepime appeared to be less active against organisms producing an ESBL, but primary and secondary resistance to imipenem was more common for P. aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia should be guided by local resistance patterns.

The inventory of antibiotics in Russian home medicine cabinets.

The objective of this study was to inventory the stock of antimicrobials in the home medicine cabinets (HMCs) of the general population in Russia and to find out for which indications people report that they would use antibiotics without a physician's recommendation. The research was performed in 9 Russian cities by physicians who visited households. An inventory of antibiotics in HMCs was made, and respondents were asked about instances in which they would choose automedication with antibiotics. We found that 83.6% of families had antibiotics for systemic use in HMCs. The most common antibiotics in HMCs were trimethoprim-sulfamethoxazole (46.3% of HMCs), ampicillin (45.1%), chloramphenicol (32.7%), erythromycin (25.5%), and tetracycline (21.8%). The major indications for automedication with antibiotics were acute viral respiratory tract infections (12.3% of total indications), cough (11.8%), intestinal disorders (11.3%), fever (9%), and sore throat (6.8%). According to this study, antibiotics are widely stocked among the general population in Russia, and people use antibiotics in an uncontrolled and imprudent manner.

Antimicrobial susceptibility of nasopharyngeal isolates of Haemophilus influenzae from healthy children in day-care centres: results of multicentre study in Russia.

Resistance of Haemophilus influenzae from clinical isolates can be predicted on the basis of results of antimicrobial susceptibility of nasopharyngeal isolates. The carriage rate and the antimicrobial susceptibility of H. influenzae isolated in healthy children attending day-care centres in Moscow, Smolensk and Yartsevo was studied. The susceptibility of ampicillin, amoxycillin/clavulanate, cefaclor, erythromycin, roxithromycin, clarithromycin and trimethoprim-sulphamethoxazole were determined by the E-test. The mean carriage rate of H. influenzae was 44%. Resistance of H. influenzae to ampicillin was 2.3%, to amoxycillin/clavulanate 0.7%, to cefaclor 0.7%, to clarithromycin 18.7% and to trimethoprim-sulphamethoxazole 21%. These included strains that showed intermediate-resistance. The antimicrobial resistance profiles varied in different centres. The clinical use of trimethoprim-sulphamethoxazole should be restricted because of the high resistance of H. influenzae to antifolate compounds.

The usage of antibiotics in Russia and some countries in Eastern Europe.

The patterns of antibiotic use in 1998 in Russia and some other countries in Eastern Europe (Belarus, Poland, Slovakia, Hungary) were studied. Poland, Slovakia and Hungary were "more modern" users of antibiotics, consuming new and expensive drugs. Russia and Belarus were "conservative" having a lower level of total consumption and using lesser quantities of penicillins, cephalosporins, macrolides, quinolones, carbapenems but greater amounts of aminoglycosides and chloramphenicol. It is essential for "conservative" countries to establish a national surveillance system of antibiotic consumption to monitor the development of bacterial resistance to antimicrobial agents and to monitor individual antibiotic use.

Antimicrobial resistance of Streptococcus pneumoniae isolated from healthy children in day-care centers: results of a multicenter study in Russia.

BACKGROUND: It has been previously shown that study of susceptibility of nasopharyngeal isolates in healthy carriers can predict resistance in clinical isolates. The purpose of this multicenter study was to determine the carriage rate of Streptococcus pneumoniae in healthy children attending day-care centers in Moscow, Smolensk and Yartsevo, Russia, and in vitro activity of penicillin G, amoxicillin/clavulanate, cefaclor, erythromycin, roxithromycin, clarithromycin and trimethoprim-sulfamethoxazole (TMP-SMX) against representative isolates. METHODS: Included in this study were 305 pneumococcal isolates from 733 children attending 9 day-care centers in Moscow, Smolensk and Yartsevo. All children enrolled in this study were <7 years of age. MICs of selected antimicrobials were determined by Etest. Serotyping of selected pneumococcal isolates was done with pool and type antisera. RESULTS: The carriage rate of S. pneumoniae in the 3 centers varied from 44.9% to 66.0% (mean, 55.9%). Susceptibility testing was performed with 305 (74.4%) of 410 isolates. Only 23 (7.5%) of 305 pneumococcal isolates were penicillin-intermediate (range, 2.8 to 12.8%) with no penicillin-resistant strains. All tested pneumococci were susceptible to amoxicillin/clavulanate. Macrolides possessed comparable activity against S. pneumoniae, at 4.6% resistant strains for both erythromycin (range, 1.1 to 17.1%) and clarithromycin (range, 1.7 to 17.1%). The highest level of resistance was observed with TMP-SMX, 53.4% (range, 43.8 to 70.9%). Of 23 strains 20 (87.0%) with intermediate resistance to penicillin were serotyped. The most prevalent serotype was 14 (5 isolates), followed by serogroups 19 (4) and 23 (4). CONCLUSIONS: Resistance to penicillin, other beta-lactams and macrolides does not seem to be a problem for Russia now. The high level of resistance to TMP-SMX considerably restricts its usage for the treatment of pneumococcal infections.

National and local antibiotic policies in Central and Eastern Europe.

To assess the antibiotic policies of Central European countries, we performed an overview of antibiotic stewardship, prescription habits and antibiotic prescription regulatory procedures. Since most Central European countries have had centralized health care and drug policies, the situation 10 years after decentralization is surprising. Only 3 of 10 Central European countries have some regulation of prescription of antibiotics, only 4 restrict some antibiotics, only 5 have hospital and only 3 national antibiotic policies. In all but 3 countries physicians can prescribe quinolones and/or 3rd generation oral cephalosporins as first-line antibiotics. Information on local and national antibiotic policies in Central and Eastern European countries is given including prescription guidelines for antibiotic use in community and hospital.