Comparative in vitro activity profile of oritavancin against recent gram-positive clinical isolates.

Oritavancin activity was tested against 15,764 gram-positive isolates collected from 246 hospital centers in 25 countries between 2005 and 2008. Organisms were Staphylococcus aureus (n = 9,075), coagulase-negative staphylococci (n = 1,664), Enterococcus faecalis (n = 1,738), Enterococcus faecium (n = 819), Streptococcus pyogenes (n = 959), Streptococcus agalactiae (n = 415), group C, G, and F streptococci (n = 84), and Streptococcus pneumoniae (n = 1,010). Among the evaluated staphylococci, 56.7% were resistant to oxacillin. The vancomycin resistance rate among enterococci was 21.2%. Penicillin-resistant and -intermediate rates were 14.7% and 21.4%, respectively, among S. pneumoniae isolates. Among nonpneumococcal streptococci, 18.5% were nonsusceptible to erythromycin. Oritavancin showed substantial in vitro activity against all organisms tested, regardless of resistance profile. The maximum oritavancin MIC against all staphylococci tested (n = 10,739) was 4 microg/ml; the MIC(90) against S. aureus was 0.12 microg/ml. Against E. faecalis and E. faecium, oritavancin MIC(90)s were 0.06 and 0.12, respectively. Oritavancin was active against glycopeptide-resistant enterococci, including VanA strains (n = 486), with MIC(90)s of 0.25 and 1 microg/ml against VanA E. faecium and E. faecalis, respectively. Oritavancin showed potent activity against streptococci (n = 2,468); MIC(90)s for the different streptococcal species were between 0.008 and 1 microg/ml. These data are consistent with previous studies with respect to resistance rates of gram-positive isolates and demonstrate the spectrum and in vitro activity of oritavancin against a wide variety of contemporary gram-positive pathogens, regardless of resistance to currently used drugs. The data provide a foundation for interpreting oritavancin activity and potential changes in susceptibility over time once oritavancin enters into clinical use.

Comparative surveillance study of telavancin activity against recently collected gram-positive clinical isolates from across the United States.

Telavancin is an investigational, rapidly bactericidal lipoglycopeptide antibiotic that is being developed to treat serious infections caused by gram-positive bacteria. A baseline prospective surveillance study was conducted to assess telavancin activity, in comparison with other agents, against contemporary clinical isolates collected from 2004 to 2005 from across the United States. Nearly 4,000 isolates were collected, including staphylococci, enterococci, and streptococci (pneumococci, beta-hemolytic, and viridans). Telavancin had potent activity against Staphylococcus aureus and coagulase-negative staphylococci (MIC range, 0.03 to 1.0 microg/ml), independent of resistance to methicillin or to multiple agents. Telavancin activity was particularly potent against all streptococcal groups (MIC(90)s, 0.03 to 0.12 microg/ml). Telavancin had excellent activity against vancomycin-susceptible enterococci (MIC(90), 1 microg/ml) and was active against VanB strains of vancomycin-resistant enterococci (MIC(90), 2 microg/ml) but less active against VanA strains (MIC(90), 8 to 16 microg/ml). Telavancin also demonstrated activity against vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus strains (MICs, 0.5 microg/ml to 1.0 microg/ml and 1.0 microg/ml to 4.0 microg/ml, respectively). These data may support the efficacy of telavancin for treatment of serious infections with a wide range of gram-positive organisms.

Effect of polysorbate 80 on oritavancin binding to plastic surfaces: implications for susceptibility testing.

Oritavancin, a semisynthetic lipoglycopeptide with activity against gram-positive bacteria, has multiple mechanisms of action, including the inhibition of cell wall synthesis and the perturbation of the membrane potential. Approved guidelines for broth microdilution MIC assays with dalbavancin, another lipoglycopeptide, require inclusion of 0.002% polysorbate 80. To investigate the potential impact of polysorbate 80 on oritavancin susceptibility assays, we quantified the recovery of [(14)C]oritavancin from susceptibility assay plates with and without polysorbate 80 and examined the effect of the presence of polysorbate 80 on the oritavancin MICs for 301 clinical isolates from the genera Staphylococcus, Enterococcus, and Streptococcus. In the absence of polysorbate 80, [(14)C]oritavancin was rapidly lost from solution in susceptibility assay test plates: 9% of the input drug was recovered in broth at 1 h when [(14)C]oritavancin was tested at 1 mug/ml. Furthermore, proportionately greater losses were observed at lower oritavancin concentrations, suggesting saturable binding of oritavancin to surfaces. The inclusion of 0.002% polysorbate 80 or 2% lysed horse blood permitted the recovery of 80 to 100% [(14)C]oritavancin at 24 h for all drug concentrations tested. Concordantly, oritavancin MIC(90)s for streptococcal isolates, as determined in medium containing 2% lysed horse blood, were identical with and without polysorbate 80. In stark contrast, polysorbate 80 reduced the oritavancin MIC(90)s by 16- to 32-fold for clinical isolates of enterococci and staphylococci, which are typically cultured without blood. The results presented here provide evidence that the MIC data for oritavancin in the current literature significantly underestimate the potency of oritavancin in vitro. Moreover, the combination of data from MIC and [(14)C]oritavancin recovery studies supports the revision of the oritavancin broth microdilution method to include polysorbate 80 throughout the assay.

In vitro activity of tigecycline against gram-positive and gram-negative pathogens as evaluated by broth microdilution and Etest.

The current surveillance establishes the activity profile of tigecycline against recent clinical U.S. isolates of target pathogens. Findings from a distributed surveillance that utilized Etest yielded a tigecycline activity profile that varied from that observed in a separate centralized broth microdilution (BMD) surveillance (D. C. Draghi et al., Poster D-0701, 46th Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA). Differences were noted among Acinetobacter spp. and Serratia marcescens and, to a lesser extent, with Streptococcus pyogenes. To address whether these differences were due to discordance in testing methodology or to variations among the analyzed populations, isolates from the current surveillance were concurrently tested by BMD and Etest. In all, 1,800 Staphylococcus aureus, 259 S. pyogenes, 226 Streptococcus pneumoniae, 93 Enterococcus faecalis, 1,356 Enterobacteriaceae, and 227 Acinetobacter baumannii strains were evaluated. Tigecycline had potent activity by BMD, with >99.6% susceptibility (%S) observed for all pathogens with interpretive criteria, excluding Enterobacter cloacae (98.3% S) and E. faecalis (86.0% S), and MIC(90)s ranged from 0.03 mug/ml (S. pyogenes/S. pneumoniae) to 1 mug/ml (Enterobacteriaceae/A. baumannii). Similar profiles were observed by Etest, with the exception of A. baumannii, although for most evaluated pathogens Etest MICs trended one doubling-dilution higher than BMD MICs. Major or very major errors were infrequent, and a high degree of essential agreement was observed, excluding A. baumannii, S. marcescens, and S. pneumoniae, for which >/=4-fold differences in MICs were observed for 29, 27.1, and 34% of the isolates, respectively. Further analysis regarding the suitability of the tigecycline Etest for testing S. marcescens, Acinetobacter spp., and S. pneumoniae is warranted.

In vitro activity of telavancin against recent Gram-positive clinical isolates: results of the 2004-05 Prospective European Surveillance Initiative.

OBJECTIVES: Telavancin is a novel semi-synthetic lipoglycopeptide currently in late-stage clinical development for the treatment of serious infections due to Gram-positive bacteria. The objective of this study was to provide a baseline prospective assessment of its in vitro activity against a large and diverse collection of Gram-positive clinical isolates from Europe and Israel. METHODS: Gram-positive clinical isolates, collected between October 2004 and December 2005 from 36 hospital laboratories in 15 countries, were tested by broth microdilution using CLSI methodology. RESULTS: In total, 3206 isolates were collected. Telavancin had potent activity against Staphylococcus aureus and coagulase-negative staphylococci (MIC range < or =0.015 to 2 mg/L), independent of resistance to methicillin or to multiple drugs. Telavancin had particularly strong activity against streptococcal isolates (MIC range < or =0.001 to 0.5 mg/L), including penicillin-resistant and multiple drug-resistant Streptococcus pneumoniae and erythromycin non-susceptible beta-haemolytic and viridans group streptococci. Telavancin also had excellent activity against vancomycin-susceptible enterococci (MIC(90) 0.5 mg/L), and although its MICs were elevated against VanA strains (Enterococcus faecalis MIC(90) 8 mg/L and Enterococcus faecium MIC(90) 4 mg/L), its MIC(90) was substantially lower than observed with available glycopeptides. CONCLUSIONS: Telavancin has potent in vitro activity against contemporary Gram-positive clinical isolates from diverse geographic areas in Europe and Israel.

Susceptibility of Staphylococcus aureus isolated from skin and wound infections in the United States 2005-07: laboratory-based surveillance study.

OBJECTIVES: The aim of this study was to describe the rates of antimicrobial susceptibility of Staphylococcus aureus from skin and wound infections reported from nine regions of the USA during 2005-07 and to identify the regional variation in patterns of resistance. METHODS: The Surveillance Network (TSN) comprises 296 laboratories across the nine census regions of the USA. TSN laboratories reported the susceptibility data for six antimicrobials by isolate with source and other relevant data. Antimicrobial susceptibility data were analysed by individual drug resistance, multidrug resistance and geographical distribution of resistance phenotypes. RESULTS: There were over 380 000 isolates of S. aureus tested and reported for the period 2005-07. Methicillin resistance was observed in 57.8% in 2007, with little change from 2005. There was little difference in rates of methicillin resistance between community and hospital strains, although strains from intensive care units (ICUs) tended to be slightly more resistant overall. Resistance to other antimicrobials was also reported. A regional variation in resistance rates was noted with the highest rates in the Central states and lowest in the New England and Mid-Atlantic regions. There was high activity observed with trimethoprim/sulfamethoxazole and gentamicin. Linezolid resistance was rare. Oxacillin resistance was similar among paediatric and elderly cohorts, whereas ciprofloxacin and clindamycin resistance was significantly (P < 0.01) more common in elderly patients when compared with both paediatric and adult populations. Less than a third of all isolates showed no resistance mechanism, 30.3%. Three distinct resistance phenotypes accounted for 46% of all resistant strains. Overall, there were more highly drug-resistant isolates from the ICU with four, five or six drug-resistant phenotypes accounting for over a third of all strains. CONCLUSIONS: S. aureus has become methicillin-resistant in both the community and hospital settings; however, little change has been seen in the past 3 years. Multiresistant strains now are seen in all settings, but due to regional variation, empirical therapy should be guided by local susceptibility patterns. Currently, among the agents studied, only trimethoprim/sulfamethoxazole, gentamicin and linezolid exhibit susceptibility rates of >95%.

Prevalence of multidrug-resistant, methicillin-resistant Staphylococcus aureus in the United States: findings of the stratified analysis of the 2004 to 2005 LEADER Surveillance Programs.

Surveillance data for methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistance (MDR) among MRSA were analyzed by patient location and age. MRSA rates were 55.7% among inpatients (53.9% MDR) and 48.7% among outpatients (30.7% MDR), with MDR rates increasing with age. These findings could impact the guidelines for the management and treatment of staphylococcal infections.

Newly defined in vitro quality control ranges for oritavancin broth microdilution testing and impact of variation in testing parameters.

A 9-laboratory M23-A2 quality control (QC) study was performed to evaluate reproducibility of oritavancin MICs against reference strains of Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae using broth microdilution assays in the presence of polysorbate 80. Polysorbate 80 has previously been shown to be required for accurate measurement of oritavancin broth microdilution MICs. Greater than 95% of replicate results (n = 270/organism) fell within the following QC ranges (in micrograms per milliliter): S. aureus ATCC 29213, 0.015 to 0.12; E. faecalis ATCC 29212, 0.008 to 0.03; and S. pneumoniae ATCC 49619, 0.001 to 0.004. Oritavancin MIC QC ranges were, thus, narrow and reproducible. Parameters affecting testing results in the presence of polysorbate 80 were also evaluated. Oritavancin MICs were equivalent to or within 1 doubling dilution of those obtained under standard Clinical and Laboratory Standards Institute testing conditions, regardless of incubation time (18, 24, or 48 h), Ca(2+) concentration, pH, or frozen panel storage time (up to 6 months).

Increasing prevalence of methicillin resistance in serious ocular infections caused by Staphylococcus aureus in the United States: 2000 to 2005.

PURPOSE: To report the nationwide prevalence of methicillin resistance in serious ocular infections involving Staphylococcus aureus and profile in vitro antimicrobial susceptibility of S aureus from ocular isolates over time. SETTING: Mount Sinai School of Medicine, New York, New York, USA. METHODS: Data on S aureus submitted to The Surveillance Network (TSN) by more than 200 laboratories in the United States from January 2000 to December 2005 were reviewed. The prevalence of methicillin resistance in S aureus ocular infections and in vitro susceptibility to antibiotic agents commonly used to treat or prevent ocular infections were determined. RESULTS: The proportion of S aureus infections culture-positive for methicillin-resistant S aureus (MRSA) increased from 29.5% in 2000 to 41.6% in 2005. The MRSA ocular isolates were multidrug resistant; that is, in vitro resistance to 3 antibiotic agents or more, including all fluoroquinolones tested. CONCLUSIONS: Multidrug-resistant MRSA is increasing in serious ocular infections. Based on the rate of increase in the TSN database, MRSA cultures from serious ocular infections could be more common than methicillin-susceptible S aureus within 2 to 3 years. Large-scale national surveillance programs are needed to monitor in vitro antimicrobial resistance trends in ocular isolates.

Baseline in vitro activity of tigecycline among key bacterial pathogens exhibiting multidrug resistance.

Tigecycline is the first clinically available semisynthetic glycylcycline approved for clinical use. This study was done to establish a baseline for ongoing surveillance of tigecycline's activity as this agent's clinical use increases. Against 1,796 Staphylococcus aureus (559 multidrug resistant), tigecycline had the lowest minimal inhibitory concentration (MIC(90); 0.12 microg/ml) among all agents tested and 99.8% of the isolates were susceptible. For Acinetobacter spp., tigecycline again demonstrated the lowest MIC(90) (2 microg/ml) and the highest percent susceptibility (96.9%). Among Enterobacteriaceae, the 2 most active agents were tigecycline (MIC(90) = 1 microg/ml; 99% susceptible) and imipenem (MIC(90) = 1 microg/ml; 99.5% susceptible). Tigecycline also demonstrated high activity against Streptococcus pneumoniae, Streptococcus pyogenes,Haemophilus influenzae and Enterococcus spp. In summary, tigecycline currently exhibits potent activity against a broad array of bacteria species. Given the dynamics of resistance development, careful monitoring of tigecycline activity against these organisms should remain a significant aspect of ongoing surveillance.

Current antimicrobial resistance profiles among methicillin-resistant Staphylococcus aureus encountered in the outpatient setting.

The acquisition of the mec gene complex by methicillin-susceptible Staphylococcus aureus in the community and the increased spread of methicillin-resistant Staphylococcus aureus (MRSA) from the health care setting to the community underscore a need to monitor the resistance phenotypes likely to be encountered among outpatient MRSA. Data from the LEADER 2004 surveillance program were analyzed to evaluate current resistance profiles among outpatient MRSA. Outpatient MRSA exhibited 26 different resistance phenotypes; the 4 most common were resistance to erythromycin only (40.8%), multidrug resistance to erythromycin, clindamycin, and levofloxacin (21.5%), double drug resistance to erythromycin and levofloxacin (11.3%), and double drug resistance to clindamycin and erythromycin (5.1%). These phenotypes were also the most common among inpatient MRSA (n = 946), but multidrug resistance to erythromycin, clindamycin, and levofloxacin (43.7%) was most common. Fifty percent (256) of the outpatient MRSA were resistant to 2 or more agents, whereas resistance to either vancomycin or linezolid was not encountered. The extensive similarities in resistance profiles between inpatient and outpatient MRSA have important implications for establishing outpatient management and treatment guidelines for staphylococcal infections.

Activity of cefditoren against beta-lactamase-positive and -negative Haemophilus influenzae and Moraxella catarrhalis.

Cefditoren is a novel broad-spectrum oral cephalosporin. To determine the influence of beta-lactamase production on cefditoren activity, 1,170 H. influenzae and 641 M. catarrhalis isolated during 2000 were tested by NCCLS broth microdilution methodology (M7-A5, 2000). Against H. influenzae the potency of cefditoren (MIC(90,) 0.015 microg/mL) was similar to that of ceftriaxone (MIC(90,) < or = 0.015 microg/mL) and levofloxacin (MIC(90,) 0.015 microg/mL), and its MIC distribution was unaffected by beta-lactamase production. In comparison, the beta-lactamase status of M. catarrhalis affected the potency of all beta-lactams tested, including cefditoren, as well as trimethoprim-sulfamethoxazole. However, regardless of the presence of beta-lactamase, cefditoren demonstrated potent activity, as concentrations of 0.5 and 1 microg/mL inhibited 93.1 and 100% of M. catarrhalis isolates, respectively. We conclude that cefditoren is highly active in vitro against beta-lactamase-positive H. influenzae and M. catarrhalis.

In vitro susceptibility of recent clinical isolates of pneumococci to the investigational cephalosporin cefditoren.

From February to June 2000, 2,597 isolates of Streptococcus pneumoniae were prospectively collected from 146 clinical laboratories across the United States (US) and tested to evaluate the in vitro activity of cefditoren, an investigational oral cephalosporin. In all, 2,492 isolates (96.0%) had a cefditoren MIC of 0.5 microg/mL or less, 74 isolates (2.8%) had an MIC of 1 microg/mL, 30 isolates (1.2%) had an MIC of 2 microg/mL, and 1 isolate (<0.1%) had an MIC of 4 microg/mL. Among the beta-lactams tested, the rank order of potency (MIC(90,) microg/mL) was cefditoren (0.5) > ceftriaxone (1) > amoxicillin-clavulanate (2) > cefuroxime (4) > cefprozil (8). Penicillin-resistant isolates (n = 443; 17.1%) were inhibited by lower concentrations (MIC(90,) microg/mL; MIC range,) of cefditoren (1; 0.03-4) than ceftriaxone (2; 0.25- > 2), amoxicillin-clavulanate (8; 0.5- > 8), cefuroxime (16; 2- > 16), and cefprozil (32; 2- > 32). Cefditoren MIC(90)s against cefuroxime-resistant (n = 640) and ceftriaxone-resistant (n = 89) isolates were 1 and 2 microg/mL, respectively. All isolates with reduced susceptibility to cefditoren (MIC, 2 or 4 microg/mL; n = 31) were resistant to penicillin, cefuroxime, and ceftriaxone. The potent in vitro activity of cefditoren against a recent US collection of pneumococci as demonstrated in this study supports its continued development for oral empiric therapy in outpatients with respiratory tract infections.

Epidemiology and antibiotic susceptibility of bacteria causing skin and soft tissue infections in the USA and Europe: a guide to appropriate antimicrobial therapy.

Susceptibility data for all organisms associated with a range of skin and soft tissue infections (SSTI) in hospitalised patients were studied. Data were reported by clinical laboratories in the USA, France, Germany, Italy and Spain during 2001 which participate in The Surveillance Network (TSN). Staphylococcus aureus, Enterococcus spp. and coagulase-negative staphylococci (CNS), Escherichia coli and Pseudomonas aeruginosa were the most prevalent pathogens in all countries. MRSA was detected in 44.4, 34.7, 12.4, 41.8 and 32. 4% of S. aureus in each country, respectively. The majority of MRSA were cross resistant to other compound classes tested except for vancomycin (100% susceptible) trimethoprim-sulphamethoxazole with range 1.7% (France) to 15.9% (Italy) resistant, and gentamicin with range 12.2% (France) to 87.0% (Italy) resistant. More than 99.0% of MSSA tested susceptible to ceftriaxone and >94.9% to trimethoprim-sulphamethoxazole. 87.2% (France) to 94.6% of MSSA (Germany) were ciprofloxacin susceptible; 73.2% (USA) to 86.6% (Spain) were erythromycin susceptible; 85.4% (Italy) to 99.2% (France) were gentamicin susceptible. MSSA were more frequently found and generally more antibiotic susceptible from out patients. Overall, 100% of Streptococcus agalactiae and Streptococcus pyogenes were susceptible to penicillin, ceftriaxone and cefotaxime. Macrolide resistance was common among S. agalactiae (20.7%, Germany to 10%, Italy and Spain), S. pyogenes (19.2%, France to 11.1%, USA) and viridans streptococci (25.7%, France to 14.1%, Germany). Vancomycin-resistant Enterococcus spp. were uncommon outside the USA (17.5%) and Italy (7.4%). For all countries susceptibility of E. coli was 100% to imipenem, >98.7% to amikacin, >96.0% to ceftriaxone and cefotaxime. Susceptibility of E. coli isolates to ciprofloxacin was 77.6% in Spain to 94.3% in Germany. Klebsiella spp., Proteus spp., Citrobacter spp. and Enterobacter spp. displayed varying susceptibilities between countries to drugs tested. Putative extended spectrum beta-lactamase expression in E. coli remained rare comprising 4-5% of isolates in USA, Italy and Spain and in France and Germany <2%. For P. aeruginosa piperacillin-tazobactam, amikacin, imipenem and ceftazidime were the most active compounds tested irrespective of region. Surveillance data should be considered when selecting empirical therapy for treating SSTI.

Antibiotic susceptibility of bacteria most commonly isolated from bone related infections: the role of cephalosporins in antimicrobial therapy.

Bone infections, which can be acute or chronic, often require aggressive antibiotic therapy, whether treated at home or in the community. Surveillance programmes are essential tools in the monitoring of antimicrobial resistance and can act as a resource to maintain effective prescribing. The Surveillance Network (TSN), which collects organism and patient-specific data from a network of laboratories across the United States, was used to analyse susceptibility of common bacterial species isolated from bone infections during 2000-2002. Narrow-spectrum antimicrobials such as vancomycin, quinupristin-dalfopristin and linezolid demonstrated good activity against Staphylococcus aureus and streptococci, and were active against 100% of isolates. However, Gram-negative species were also commonly isolated from these sites of infection. Later-generation cephalosporins, represented by ceftriaxone, cefotaxime and cefepime, exhibited a broad spectrum of activity including Enterobacteriaceae, streptococci and methicillin-susceptible S. aureus, but they were not active against methicillin-resistant S. aureus (MRSA) and showed variable activity against Pseudomonas aeruginosa. Using ceftazidime as a marker for extended spectrum beta-lactamase (ESBL) expression, less than 3% of Escherichia coli or Klebsiella pneumoniae expressed this phenotype. Based on current in vitro activity, the third-generation cephalosporins provide broad-spectrum coverage useful for the empirical therapy of suspected bone infections, especially for patients treated in the community or hospitalised with community-acquired infections.

Antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in two successive respiratory seasons in the US.

Antimicrobial susceptibilities of clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were determined in two consecutive respiratory seasons in the US and suggested that national susceptibilities to commonly tested antimicrobials changed only slightly from the 1999-2000 to the 2000-2001 respiratory season. However, a significant regional variation in S. pneumoniae susceptibilities was observed, as was a decrease in beta-lactamase rates among H. influenzae from the 1999-2000 to 2000-2001 respiratory seasons.

Prevalence of antimicrobial resistance in bacteria isolated from central nervous system specimens as reported by U.S. hospital laboratories from 2000 to 2002.

BACKGROUND: Bacterial infections of the central nervous system, especially acute infections such as bacterial meningitis require immediate, invariably empiric antibiotic therapy. The widespread emergence of resistance among bacterial species is a cause for concern. Current antibacterial susceptibility data among central nervous system (CNS) pathogens is important to define current prevalence of resistance. METHODS: Antimicrobial susceptibility of pathogens isolated from CNS specimens was analyzed using The Surveillance Database (TSN) USA Database which gathers routine antibiotic susceptibility data from >300 US hospital laboratories. A total of 6029 organisms derived from CNS specimen sources during 2000-2002, were isolated and susceptibility tested. RESULTS: Staphylococcus aureus (23.7%) and Streptococcus pneumoniae (11.0%) were the most common gram-positive pathogens. Gram-negative species comprised approximately 25% of isolates. The modal patient age was 1 or <1 year for most organisms. Prevalence of MRSA among S. aureus from cerebrospinal fluid (CSF) and brain abscesses were 29.9-32.9%. Penicillin resistance rates were 16.6% for S. pneumoniae, 5.3% for viridans group streptococci, and 0% for S. agalactiae. For CSF isolates, ceftriaxone resistance was S. pneumoniae (3.5%), E. coli (0.6%), Klebsiella pneumoniae (2.8%), Serratia marcescens (5.6%), Enterobacter cloacae (25.0%), Haemophilus influenzae (0%). Listeria monocytogenes and N. meningitidis are not routinely susceptibility tested. CONCLUSIONS: Resistance is commonly detected, albeit still at relatively low levels for key drugs classes such as third-generation cephalosporins. This data demonstrates the need to consider predominant resistance phenotypes when choosing empiric therapies to treat CNS infections.

Prevalence and antimicrobial susceptibilities of bacteria isolated from blood cultures of hospitalized patients in the United States in 2002.

BACKGROUND: Bloodstream infections are associated with significant patient morbidity and mortality. Antimicrobial susceptibility patterns should guide the choice of empiric antimicrobial regimens for patients with bacteremia. METHODS: From January to December of 2002, 82,569 bacterial blood culture isolates were reported to The Surveillance Network (TSN) Database-USA by 268 laboratories. Susceptibility to relevant antibiotic compounds was analyzed using National Committee for Clinical Laboratory Standards guidelines. RESULTS: Coagulase-negative staphylococci (42.0%), Staphylococcus aureus (16.5%), Enterococcus faecalis (8.3%), Escherichia coli (7.2%), Klebsiella pneumoniae (3.6%), and Enterococcus faecium (3.5%) were the most frequently isolated bacteria from blood cultures, collectively accounting for >80% of isolates. In vitro susceptibility to expanded-spectrum beta-lactams such as ceftriaxone were high for oxacillin-susceptible coagulase-negative staphylococci (98.7%), oxacillin-susceptible S. aureus (99.8%), E. coli (97.3%), K. pneumoniae (93.3%), and Streptococcus pneumoniae (97.2%). Susceptibilities to fluoroquinolones were variable for K. pneumoniae (90.3-91.4%), E. coli (86.0-86.7%), oxacillin-susceptible S. aureus (84.0-89.4%), oxacillin-susceptible coagulase-negative staphylococci (72.7-82.7%), E. faecalis (52.1%), and E. faecium (11.3%). Combinations of antimicrobials are often prescribed as empiric therapy for bacteremia. Susceptibilities of all blood culture isolates to one or both agents in combinations of ceftriaxone, ceftazdime, cefepime, piperacillin-tazobactam or ciprofloxacin plus gentamicin were consistent (range, 74.8-76.3%) but lower than similar beta-lactam or ciprofloxacin combinations with vancomycin (range, 93.5-96.6%). CONCLUSION: Ongoing surveillance for antimicrobial susceptibility remains essential, and will enhance efforts to identify resistance and attempt to limit its spread.

Tracking the implementation of NCCLS M100-S12 expanded-spectrum cephalosporin MIC breakpoints for nonmeningeal isolates of Streptococcus pneumoniae by clinical laboratories in the United States during 2002 and 2003.

BACKGROUND: The Performance Standards for Antimicrobial Susceptibility Testing, Twelfth Informational Supplement, M100-S12, published by the National Committee for Clinical Laboratory Standards (NCCLS) in January 2002 introduced distinct minimum inhibitory concentration (MIC) interpretative breakpoints for ceftriaxone, cefotaxime, and cefepime for nonmeningeal isolates of Streptococcus pneumoniae. Previously, a single set of interpretative breakpoints was used for both meningeal and nonmeningeal isolates. METHODS: To estimate the rate of adoption of the M100-S12 interpretive breakpoints by clinical laboratories, antimicrobial susceptibility test results for ceftriaxone and cefotaxime from nonmeningeal S. pneumoniae isolates were studied using data collected from January 2002 to June 2003 by The Surveillance Network Database--USA (TSN, an electronic surveillance database. RESULTS: Of the 262 laboratories that provided data that could be evaluated, 67.6% had adopted the M100-S12 breakpoints one and one-half years after they were published. CONCLUSIONS: The NCCLS M100-S12 recommendation to interpret MICs to expanded-spectrum cephalosporins using two distinct sets of breakpoints for meningeal and nonmeningeal isolates of S. pneumoniae was steadily implemented by clinical microbiology laboratories in the United States following their initial publication in January 2002. The use of these new breakpoints more accurately reflects the clinical activities of expanded-spectrum cephalosporins than did the single set of interpretative breakpoints previously used for both meningeal and nonmeningeal isolates.

Emerging resistance among bacterial pathogens in the intensive care unit--a European and North American Surveillance study (2000-2002).

BACKGROUND: Globally ICUs are encountering emergence and spread of antibiotic-resistant pathogens and for some pathogens there are few therapeutic options available. METHODS: Antibiotic in vitro susceptibility data of predominant ICU pathogens during 2000-2 were analyzed using data from The Surveillance Network (TSN) Databases in Europe (France, Germany and Italy), Canada, and the United States (US). RESULTS: Oxacillin resistance rates among Staphylococcus aureus isolates ranged from 19.7% to 59.4%. Penicillin resistance rates among Streptococcus pneumoniae varied from 2.0% in Germany to as high as 20.2% in the US; however, ceftriaxone resistance rates were comparably lower, ranging from 0% in Germany to 3.4% in Italy. Vancomycin resistance rates among Enterococcus faecalis were < or = 4.5%; however, among Enterococcus faecium vancomycin resistance rates were more frequent ranging from 0.8% in France to 76.3% in the United States. Putative rates of extended-spectrum beta-lactamase (ESBL) production among Enterobacteriaceae were low, <6% among Escherichia coli in the five countries studied. Ceftriaxone resistance rates were generally lower than or similar to piperacillin-tazobactam for most of the Enterobacteriaceae species examined. Fluoroquinolone resistance rates were generally higher for E. coli (6.5% - 13.9%), Proteus mirabilis (0-34.7%), and Morganella morganii (1.6-20.7%) than other Enterobacteriaceae spp (1.5-21.3%). P. aeruginosa demonstrated marked variation in beta-lactam resistance rates among countries. Imipenem was the most active compound tested against Acinetobacter spp., based on resistance rates. CONCLUSION: There was a wide distribution in resistance patterns among the five countries. Compared with other countries, Italy showed the highest resistance rates to all the organisms with the exception of Enterococcus spp., which were highest in the US. This data highlights the differences in resistance encountered in intensive care units in Europe and North America and the need to determine current local resistance patterns by which to guide empiric antimicrobial therapy for intensive care infections.