Ceftobiprole Compared With Vancomycin Plus Aztreonam in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Results of a Phase 3, Randomized, Double-blind Trial (TARGET).

BACKGROUND: The development of novel broad-spectrum antibiotics, with efficacy against both gram-positive and gram-negative bacteria, has the potential to enhance treatment options for acute bacterial skin and skin structure infections (ABSSSIs). Ceftobiprole is an advanced-generation intravenous cephalosporin with broad in vitro activity against gram-positive (including methicillin-resistant Staphylococcus aureus) and gram-negative pathogens. METHODS: TARGET was a randomized, double-blind, active-controlled, parallel-group, multicenter, phase 3 noninferiority study that compared ceftobiprole with vancomycin plus aztreonam. The Food and Drug Administration-defined primary efficacy endpoint was early clinical response 48-72 hours after treatment initiation in the intent-to-treat (ITT) population and the European Medicines Agency-defined primary endpoint was investigator-assessed clinical success at the test-of-cure (TOC) visit. Noninferiority was defined as the lower limit of the 95% CI for the difference in success rates (ceftobiprole minus vancomycin/aztreonam) >-10%. Safety was assessed through adverse event and laboratory data collection. RESULTS: In total, 679 patients were randomized to ceftobiprole (n = 335) or vancomycin/aztreonam (n = 344). Early clinical success rates were 91.3% and 88.1% in the ceftobiprole and vancomycin/aztreonam groups, respectively, and noninferiority was demonstrated (adjusted difference: 3.3%; 95% CI: -1.2, 7.8). Investigator-assessed clinical success at the TOC visit was similar between the 2 groups, and noninferiority was demonstrated for both the ITT (90.1% vs 89.0%) and clinically evaluable (97.9% vs 95.2%) populations. Both treatment groups displayed similar microbiological success and safety profiles. CONCLUSIONS: TARGET demonstrated that ceftobiprole is noninferior to vancomycin/aztreonam in the treatment of ABSSSIs, in terms of early clinical response and investigator-assessed clinical success at the TOC visit. CLINICAL TRIALS REGISTRATION: NCT03137173.

Safety, Tolerability, and Population Pharmacokinetics of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients.

Isavuconazole, administered as the water-soluble prodrug isavuconazonium sulfate, is a new triazole agent used to treat invasive fungal infections. This phase 1 study evaluated the pharmacokinetics (PK), safety, and tolerability of isavuconazole in 46 immunocompromised pediatric patients, stratified by age (1 to <6 [intravenous (i.v.) only], 6 to <12, and 12 to <18 years), receiving 10 mg/kg body weight (maximum, 372 mg) isavuconazonium sulfate either i.v. or orally. A population PK model using weight-based allometric scaling was constructed with the pediatric i.v. and oral data plus i.v. data from a phase 1 study in adults. The best model was a 3-compartment model with combined zero-order and first-order input, with linear elimination. Stepwise covariate modeling was performed in Perl-speaks-NONMEM version 4.7.0. None of the covariates examined, including age, sex, race, and body mass index, were statistically significant for any of the PK parameters. The area under the concentration-time curve at steady state (AUCSS) was predicted for pediatric patients using 1,000 Monte Carlo simulations per age cohort for each administration route. The probability of target attainment (AUCSS range, 60 to 233 µg · h/ml) was estimated; this target range was derived from plasma drug exposures in adults receiving the recommended clinical dose. Predicted plasma drug exposures were within the target range for >80% and >76% of simulated pediatric patients following i.v. or oral administration, respectively. Intravenous and oral administration of isavuconazonium sulfate at the studied dosage of 10 mg/kg was well tolerated and resulted in exposure in pediatric patients similar to that in adults. (This study has been registered at ClinicalTrials.gov under identifier NCT03241550).

Outcomes by MIC Values for Patients Treated with Isavuconazole or Voriconazole for Invasive Aspergillosis in the Phase 3 SECURE and VITAL Trials.

This pooled analysis evaluated the relationship of isavuconazole and voriconazole MICs of Aspergillus pathogens at baseline with all-cause mortality and clinical outcomes following treatment with either drug in the SECURE and VITAL trials. Isavuconazole and voriconazole may have had reduced efficacy against pathogens with drug MICs of ≥16 µg/ml, but there was no relationship with clinical outcomes in cases where the MIC was <16 µg/ml for either drug.

Perspectives of older adults on co-management of low back pain by doctors of chiropractic and family medicine physicians: a focus group study.

BACKGROUND: While older adults may seek care for low back pain (LBP) from both medical doctors (MDs) and doctors of chiropractic (DCs), co-management between these providers is uncommon. The purposes of this study were to describe the preferences of older adults for LBP co-management by MDs and DCs and to identify their concerns for receiving care under such a treatment model. METHODS: We conducted 10 focus groups with 48 older adults who received LBP care in the past year. Interviews explored participants' care seeking experiences, co-management preferences, and perceived challenges to successful implementation of a MD-DC co-management model. We analyzed the qualitative data using thematic content analysis. RESULTS: Older adults considered LBP co-management by MDs and DCs a positive approach as the professions have complementary strengths. Participants wanted providers who worked in a co-management model to talk openly and honestly about LBP, offer clear and consistent recommendations about treatment, and provide individualized care. Facilitators of MD-DC co-management included collegial relationships between providers, arrangements between doctors to support interdisciplinary referral, computer systems that allowed exchange of health information between clinics, and practice settings where providers worked in one location. Perceived barriers to the co-management of LBP included the financial costs associated with receiving care from multiple providers concurrently, duplication of tests or imaging, scheduling and transportation problems, and potential side effects of medication and chiropractic care. A few participants expressed concern that some providers would not support a patient-preferred co-managed care model. CONCLUSIONS: Older adults are interested in receiving LBP treatment co-managed by MDs and DCs. Older adults considered patient-centered communication, collegial interdisciplinary interactions between these providers, and administrative supports such as scheduling systems and health record sharing as key components for successful LBP co-management.

Extraction of small boat harmonic signatures from passive sonar.

This paper investigates the extraction of acoustic signatures from small boats using a passive sonar system. Noise radiated from a small boats consists of broadband noise and harmonically related tones that correspond to engine and propeller specifications. A signal processing method to automatically extract the harmonic structure of noise radiated from small boats is developed. The Harmonic Extraction and Analysis Tool (HEAT) estimates the instantaneous fundamental frequency of the harmonic tones, refines the fundamental frequency estimate using a Kalman filter, and automatically extracts the amplitudes of the harmonic tonals to generate a harmonic signature for the boat. Results are presented that show the HEAT algorithms ability to extract these signatures.

Ceftobiprole versus daptomycin in Staphylococcus aureus bacteremia: a novel protocol for a double-blind, Phase III trial.

Although Staphylococcus aureus is a common cause of bacteremia, treatment options are limited. The need for new therapies is particularly urgent for methicillin-resistant S. aureus bacteremia (SAB). Ceftobiprole is an advanced-generation, broad-spectrum cephalosporin with activity against both methicillin-susceptible and -resistant S. aureus. This is a Phase III, randomized, double-blind, active-controlled, parallel-group, multicenter, two-part study to establish the efficacy and safety of ceftobiprole compared with daptomycin in the treatment of SAB, including infective endocarditis. Anticipated enrollment is 390 hospitalized adult patients, aged ≥18 years, with confirmed or suspected complicated SAB. The primary end point is overall success rate. Target completion of the study is in the second half of 2021. Clinicaltrials.gov identifier: NCT03138733.

Evaluation of reagents used to coat the hollow-fiber bioreactor membrane of the Quantum® Cell Expansion System for the culture of human mesenchymal stem cells.

The addition of a coating reagent to promote cell adherence is necessary to prepare the membrane surface of the Quantum® Cell Expansion System hollow-fiber bioreactor for the culture of mesenchymal stem cells. In this study, the efficacy of 8 potential coating reagents has been compared in terms of the doubling times of their cell populations, cell morphology, characterization via flow cytometry, and capacity for trilineage differentiation. Human fibronectin (FN), pooled human cryoprecipitate (CPPT), and recombinant human vitronectin (VN) were successful as coating reagents, and each product has advantages in different cell culture contexts. Mesenchymal stem cells harvested from Quantum cultured with each of these 3 compounds as coating reagents all met International Society for Cellular Therapy standards for plastic adherence, surface marker expression, and successful trilineage differentiation. No significant differences were observed among the doubling times from Quantum harvests using FN, CPPT, or VN as coating reagents (P = 0.31). Coating with gelatin, human serum albumin, collagen I, poly­l­lysine, and poly­d­lysine resulted in significantly lower harvest yield; these agents are not recommended for use as coating reagents in the Quantum system.

Differences between ceftriaxone and cefotaxime: microbiological inconsistencies.

OBJECTIVE: To review data to determine why pneumococcal isolates appear to be increasingly resistant to cefotaxime, historically regarded as having the same in vitro susceptibility to ceftriaxone, and what this observation might imply clinically. DATA SOURCES: Literature was accessed through MEDLINE (1966-October 2007) using the MeSH terms cefotaxime, ceftriaxone, susceptibility, microbial sensitivity tests, antibiotics, pneumococcal infections, Streptococcus pneumoniae, resistance, and cephalosporin resistance. Abstracts and surveillance databases were reviewed and unpublished data were provided by state departments of health and institutions. STUDY SELECTION AND DATA EXTRACTION: All articles published in the English language that were identified from the data sources were evaluated. DATA SYNTHESIS: An experimental model of pneumococcal infection in mice conducted 2 decades ago predicted that the delta T minimum inhibitory concentration (MIC) varied less for ceftriaxone than for cefotaxime. Studies of plasma and serum concentrations show that ceftriaxone remains at a concentration above the S. pneumoniae MIC for 100% of the dosing interval at 12 hours. Types of MIC susceptibility test methods for ceftriaxone and cefotaxime used against S. pneumoniae respiratory isolates were found to be similar. Data from state and county health departments found microbiological discrepancies between ceftriaxone and cefotaxime. In areas with high rates of penicillin-resistant S. pneumoniae (PRSP), isolates were twice as susceptible to ceftriaxone versus cefotaxime. Surveillance databases consistently show differences between susceptibility of S. pneumoniae to cefotaxime versus ceftriaxone over time. MIC and pulsed-field gel electrophoresis studies suggest that phenotypic discrepancies may account for penicillin resistance. Ongoing studies are examining S. pneumoniae isolates at the molecular level to determine the basis of difference in resistance to cefotaxime and ceftriaxone. CONCLUSIONS: An increase in rates of PRSP and differences in S. pneumoniae isolate susceptibility between ceftriaxone and cefotaxime emphasize the necessity for hospital laboratories to detect these changes as they occur. Clinicians should select the most appropriate agent for patients with S. pneumoniae.

Contracting, prompting, and reinforcing substance use disorder continuing care: a randomized clinical trial.

Although continuing care is strongly related to positive treatment outcomes for substance use disorder (SUD), participation rates are low and few effective interventions are available. In a randomized clinical trial with 150 participants (97% men), 75 graduates of a residential Veterans Affairs Medical Center SUD program who received an aftercare contract, attendance prompts, and reinforcers (CPR) were compared to 75 graduates who received standard treatment (STX). Among CPR participants, 55% completed at least 3 months of aftercare, compared to 36% in STX. Similarly, CPR participants remained in treatment longer than those in STX (5.5 vs. 4.4 months). Additionally, CPR participants were more likely to be abstinent compared to STX (57% vs. 37%) after 1 year. The CPR intervention offers a practical means to improve adherence among individuals in SUD treatment.

Stable antimicrobial susceptibility rates for clinical isolates of Pseudomonas aeruginosa from the 2001-2003 tracking resistance in the United States today surveillance studies.

From 2001 to 2003, rates of susceptibility to piperacillin-tazobactam (86%), ceftazidime (80%), ciprofloxacin (68%), and levofloxacin (67%) did not decrease or decreased by <1.5%, whereas the rate of susceptibility to gentamicin decreased by 3.2% (from 75.5% to 72.3%) and the rate of susceptibility to imipenem decreased by 5.6% (from 84.4% to 78.8%), for 2394 clinical isolates of Pseudomonas aeruginosa collected in the Tracking Resistance in the United States Today surveillance studies. Rates of multidrug resistance (i.e., resistance to > or =3 antimicrobial agents) increased from 7.2% in 2001 to 9.9% in 2003 and were significantly higher for isolates from the East North Central and Mid-Atlantic regions of the United States than for isolates from other regions. Analysis of minimum inhibitory concentrations (MICs) suggested that combining an antipseudomonal beta -lactam with ciprofloxacin or levofloxacin would yield a 3.4%-7.1% increase in the percentage of isolates susceptible to the combination, compared with the beta -lactam alone. Ratios of the area under the serum concentration-time curve values for free drug to modal MICs for ciprofloxacin and levofloxacin were similar and were >125 (target ratio), whereas those ratios for gatifloxacin and moxifloxacin were significantly lower. Ongoing surveillance of P. aeruginosa is essential.

Susceptibility of antimicrobial-resistant urinary Escherichia coli isolates to fluoroquinolones and nitrofurantoin.

In vitro surveillance data from across the United States indicate that approximately 10%-20% of urinary Escherichia coli isolates from female outpatients are resistant to trimethoprim-sulfamethoxazole (TMP-SMX). Alternative therapies for uncomplicated urinary tract infections in women include fluoroquinolones and nitrofurantoin, but the activities of these agents against TMP-SMX-resistant isolates are rarely reported. Among TMP-SMX-resistant urinary E. coli isolates tested in US laboratories from 1998 through 2001, 9.5% (5767 of 60,414) were resistant to ciprofloxacin and 1.9% (1214 of 63,817) were resistant to nitrofurantoin; 10.4% of ciprofloxacin-resistant isolates (683 of 6560) were resistant to nitrofurantoin. An association between resistance to fluoroquinolones and nitrofurantoin in E. coli has not been previously reported and warrants further study.

Regional trends in antimicrobial resistance among clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States: results from the TRUST Surveillance Program, 1999-2000.

The ongoing TRUST (Tracking Resistance in the United States Today) study, which began monitoring antimicrobial resistance among respiratory pathogens in 1996, routinely tracks resistance at national and regional levels. The 1999-2000 TRUST study analyzed 9499 Streptococcus pneumoniae, 1934 Haemophilus influenzae, and 1108 Moraxella catarrhalis isolates that were prospectively collected from 239 laboratories across the 9 US Bureau of the Census regions. Penicillin-resistant S. pneumoniae varied significantly by region, from 8.3% to 24.8% (P<.001). In each region, penicillin resistance closely predicted resistance to other beta-lactams, macrolides, and trimethoprim-sulfamethoxazole. Levofloxacin resistance was 0.5% nationally (regional range, 0.1%-1.0%). Multidrug resistance also varied significantly (P<.001) by region. beta-Lactamase production among H. influenzae varied significantly (regional range, 24.0%-34.6%) and M. catarrhalis (86.2%-96.8%) also varied by region. Notable variation in regional antimicrobial resistance rates (S. pneumoniae) and beta-lactamase production (H. influenzae, M. catarrhalis) exists throughout the United States.

Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998-2002).

To identify factors associated with antimicrobial resistance, data were analyzed from 27,828 isolates of Streptococcus pneumoniae submitted to the Tracking Resistance in the United States Today (TRUST) surveillance program during 4 consecutive respiratory seasons. From the 1998-1999 season to the 2001-2002 season, the prevalence of azithromycin resistance increased by 4.8% to 27.5%, the prevalence of penicillin resistance increased by 3.7% to 18.4%, the prevalence of ceftriaxone resistance increased by 0.5% to 1.7%, and the prevalence of levofloxacin resistance increased by 0.3% to 0.9%. Isolates recovered from patients <18 years of age and lower respiratory tract specimens had elevated rates of penicillin, azithromycin, and trimethoprim-sulfamethoxazole resistance (P<.00001); penicillin resistance correlated with coresistance to trimethoprim-sulfamethoxazole (87.3%), azithromycin (76.3%), ceftriaxone (9.1%), and levofloxacin (1.3%) (P<.00001). Only 62 (0.2%) of 27,828 isolates were concurrently resistant to penicillin and levofloxacin. Minimum inhibitory concentrations (MICs) of penicillin correlated strongly with MICs of ceftriaxone (R2=0.90), trimethoprim-sulfamethoxazole (R2=0.53), and azithromycin (R2=0.41). Patient age, specimen source, and penicillin resistance were factors associated with antimicrobial resistance, particularly for nonfluoroquinolone antimicrobial agents.

The activity of levofloxacin and other antimicrobials against clinical isolates of Streptococcus pneumoniae collected worldwide during 1999-2002.

Streptococcus pneumoniae is the most important causative bacterial pathogen in respiratory infections. Globally, increasing levels of resistant strains highlight the need for continued surveillance programs to guide antibiotic choice. The current study compared susceptibility results of 4,788 strains of S. pneumoniae collected during 2001-2002 to susceptibility results from 3,884 strains collected from the same hospitals during 1999-2000. Participant centers were dispersed throughout five regions. By region, the prevalence of penicillin-resistant S. pneumoniae and percentage change from the previous 1999-2000 study was Mexico (26.0%, 12.5%), Brazil (7.9%; 5.5%), Asia (China, Hong Kong, South Korea, Thailand) (44.1%; 0.8%), Europe (France, Germany, Italy, Spain, UK) (11.1%; -0.6%) and South Africa (7.9; -1.8%). Multidrug-resistant (MDR) strains of S. pneumoniae were most frequently isolated from Asia (36.3%) compared with approximately 5% in the other four regions. Increases in the incidence of MDR isolates in Mexico (13.5%), Brazil (1.7%) and Asia (6.1%) were reported with no increases in MDR in South Africa and Europe. Levofloxacin resistance was rarely associated with MDR phenotypes. Levofloxacin maintained an MIC(90) of 1 microg/ml against the isolates collected from all five regions with no change during the study periods, despite differences in levofloxacin resistance rates between regions or nations (0%-3.2%). The prevalence of levofloxacin resistance (MIC > or =8 microg/ml) increased only slightly over the study period in Europe (0.3%-0.7%) and in Asia (3.0-3.2%), but little or no change was seen in Mexico (3.8%-0%) or Brazil or South Africa, where no levofloxacin resistant isolates were detected in either study period.

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.

Antimicrobial susceptibilities of Streptococcus pyogenes isolated from respiratory and skin and soft tissue infections: United States LIBRA surveillance data from 1999.

This study evaluated current levels of antimicrobial resistance and associated demographic trends among clinical isolates of Streptococcus pyogenes in the United States as part of the LIBRA surveillance initiative. In 1999, 2,742 isolates of S. pyogenes (2,039 respiratory; 405 skin and soft tissue; 148 blood) were collected from 324 clinical laboratories and centrally tested for antimicrobial susceptibility by the broth microdilution method. All isolates were susceptible to penicillin (MIC(90,) < or = 0.06 microg/mL), ceftriaxone (MIC(90,) < or =0.03 microg/mL), vancomycin (MIC(90,) 0.5 microg/mL), levofloxacin (MIC(90,) 1 microg/mL), and moxifloxacin (MIC(90,) 0.25 microg/mL). Twenty-four (0.9%) azithromycin-intermediate (MIC, 1 microg/mL) and 170 (6.2%) azithromycin-resistant (MIC, > or = 2 microg/mL) isolates were identified. Regionally, azithromycin resistance varied by < 5%, ranging from 3.0% in New England to 7.7% in the Pacific region. Azithromycin resistance was significantly higher (P < 0.001) among patients aged 15-64 years (8.3%) than patients < or =14 years (4.3%). This study found higher rates of macrolide resistance among S. pyogenes than previously reported in the United States and suggests that macrolide resistance is common among respiratory isolates from both younger and older patients. Fluoroquinolones (moxifloxacin > levofloxacin) demonstrated potent in vitro activity against all isolates of S. pyogenes tested, including those from skin and soft tissue infections. Given the higher rates of macrolide resistance reported in other countries and the seriousness of invasive infections, continued antimicrobial surveillance of S. pyogenes in the United States would be prudent.

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.