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PubMed2006

Hospital- and community-acquired infections: a point prevalence and risk factors survey in a tertiary care center in Saudi Arabia.

BACKGROUND: Point prevalence studies are useful in revealing the prevalence of hospital-acquired infections (HAIs) and community-acquired infections (CAIs). Such information allows prioritization of infection control resources and aids in overall hospital expenditure cut-backs. METHODS: A one-day point prevalence survey was conducted on May 19, 2003 at the King Fahad National Guard Hospital in Riyadh. Since the survey included HAIs and CAIs all patients were included. Data were collected on the underlying diagnosis, infection if present and whether it was hospital-acquired or community-acquired. We identified the presence of a line-associated blood stream infection (BSI), ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (UTI) or a surgical site infection (SSI) based on the United States National Nosocomial Infection Surveillance (NNIS) definitions. RESULTS: Five hundred and sixty-two inpatients were included in the survey. There were 38 patients with 45 (8.0%) HAIs and 76 (13.5%) patients with a CAI. Of the HAIs, 31.1% had a line-related BSI, while 28.9% and 24.4% had a VAP and catheter-related UTI, respectively. Most of the HAIs took place in the intensive care units (ICU) (21 (46.7%)), followed by the medical and surgical wards with six (13.3%) cases in each ward. For all HAIs there was a 12.7-fold increased risk with a hospital stay exceeding eight days (OR: 12.7, CI 3.2-50.6). Most of the 76 CAIs were admitted to the medical ward with community-acquired pneumonia (34.9%) as the most common diagnosis. Among the 89 pathogens isolated, Pseudomonas aeruginosa was the most common (21.3%) followed by Enterococcus spp (16.9%). CONCLUSIONS: The overall rate of HAIs in our hospital was 8%, with significant risk factors including a hospital stay exceeding eight days. A device-related infection was more likely in a patient with a venous or bladder catheter in place for more than eight days, or a patient mechanically ventilated for more than eight days. Catheter-related UTIs were identified as an important source of infection, requiring ongoing surveillance.

Adolescent↗

PubMed2005

Prevalence of hospital-acquired infections in a home care setting.

The aim of this point-prevalence study was to determine the prevalence of hospital-acquired infections (HAIs) by site of infection and the associated risk factors in a 'hospital at home' setting in Paris. All patients undergoing a care procedure with a risk of infection and who had been in home care for more than 48 h on the day of the survey (5 June 2000) were enrolled. A standard questionnaire was completed by nurses, midwives and family doctors. Overall, 6.1% of patients had at least one HAI [95% confidence intervals (CI): 3.7-8.5%] and there were 6.3 infections per 100 patients (infections/infected patients ratio: 1.04). The most common site of infection was the urinary tract (50.0%), followed by the skin (37.9%). Infection rates were 3.2% and 2.4%, respectively. Escherichia coli (29.4%), Staphylococcus aureus (29.4%) and Enterococcus spp. (17.6%) were the predominant micro-organisms. In multivariate analysis, the most significant independent risk factor was the presence of a urinary catheter (odds ratio=15.9, 95%CI: 6.3-40.1, P<0.0001). In conclusion, this prevalence study has provided a better understanding of the types of patient receiving 'hospital at home' care, an insight into risk factors for HAIs in home care, and a basis for improving surveillance and prevention.

Adolescent↗

PubMed2025

Antibody responses in Klebsiella pneumoniae bloodstream infection: a prospective cohort study.

BACKGROUND: Klebsiella pneumoniae is a leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive K pneumoniae. We sought to determine whether the O-specific polysaccharide antigen is immunogenic in humans with K pneumoniae bloodstream infection. We also sought to define the cross-reactivity of human antibody responses among structurally related K pneumoniae O-specific polysaccharide subtypes and to assess the effect of capsule production on O-specific polysaccharide-targeted antibody binding and function. METHODS: In this prospective cohort study, we compared plasma antibody responses to O-specific polysaccharide in a cohort of consecutively enrolled patients with K pneumoniae bloodstream infection with controls, specifically a cohort of healthy individuals and a cohort of individuals with Enterococcus spp bloodstream infection. Patients were enrolled at the Massachusetts General Hospital, a tertiary hospital with affiliated clinics in the USA. We excluded patients whose isolates were not confirmed to be K pneumoniae by whole-genome sequencing. The primary outcome was the measurement of plasma IgG, IgM, and IgA antibody responses. We performed flow cytometry to measure the effects of K pneumoniae capsule production on O-specific polysaccharide antibody binding and O-specific polysaccharide antibody-mediated complement deposition, using patient isolates with variable levels of capsule production and isogenic capsule-deficient strains derived from these isolates. FINDINGS: We enrolled 129 consecutive patients with suspected K pneumoniae bloodstream infection between July 24, 2021, and August 4, 2022, of whom 69 patients (44 [64%] male and 25 [36%] female) with confirmed K pneumoniae bloodstream infection were eligible for immunological evaluation. Common O-specific polysaccharide serotypes (O1, O2, O3, and O5) accounted for 57 (83%) of 69 infections. O-specific polysaccharide was immunogenic in patients with K pneumoniae bloodstream infection, and peak O-specific polysaccharide-IgG antibody responses in patients were ten-fold to 30-fold higher than antibody responses detected in healthy controls, depending on the serotype. There was cross-reactivity among similar O-specific polysaccharide subtypes, including the O1v1 and O1v2, O2v1 and O2v2, and O3 and O3b subtypes, as well as between the O1 and O2 types. Capsule produced by both hyperencapsulated and non-hyperencapsulated K pneumoniae inhibited O-specific polysaccharide-targeted antibody binding and function. INTERPRETATION: O-specific polysaccharide was immunogenic in patients with K pneumoniae bloodstream infection, supporting its potential as a candidate vaccine antigen. The cross-reactivity observed between similar O-specific polysaccharide subtypes in patients with K pneumoniae bloodstream infection suggests that it might not be necessary to include all subtypes in an O-specific polysaccharide-based vaccine. However, these observations are tempered by the fact that capsule production, even in non-highly encapsulated strains, has the potential to interfere with O-specific polysaccharide antibody binding. This finding could limit the effectiveness of vaccines that exclusively target O-specific polysaccharide. FUNDING: National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Humans↗

PubMed2005

Bacteriospermia in extended porcine semen.

Bacteriospermia is a frequent finding in freshly extended porcine semen and can result in detrimental effects on semen quality and longevity if left uncontrolled. The primary source of bacterial contamination is the boar. Other sources that have been identified include environment, personnel, and the water used for extender preparation. A 1-year retrospective study was performed on submissions of extended porcine semen for routine quality control bacteriological screening at the University of Pennsylvania. Out of 250 sample submissions, 78 (31.2%) tested positive for bacterial contamination. The most popular contaminants included Enterococcus spp. (20.5%), Stenotrophomonas maltophilia (15.4%), Alcaligenes xylosoxidans (10.3%), Serratia marcescens (10.3%), Acinetobacter lwoffi (7.7%), Escherichia coli (6.4%), Pseudomonas spp. (6.4%), and others (23.0%). Prudent individual hygiene, good overall sanitation, and regular monitoring can contribute greatly in controlling bacterial load. Strategies that incorporate temperature-dependent bacterial growth and hyperthermic augmentation of antimicrobial activity are valuable for effective control of susceptible bacterial loads. Aminoglycosides remain the most popular antimicrobial class used in porcine semen extenders, with beta-lactam and lincosamide use increasing. With the advent of more novel antimicrobial selection and semen extender compositions in swine, prudent application and understanding of in vitro pharmacodynamics are becoming paramount to industry success in the use of this breeding modality.

Animals↗

PubMed2005

The effect of hygienic treatment on the microbial flora of biowaste at biogas plants.

In Sweden, full-scale, commercial biogas plants (BGP), which process low-risk animal waste, operate a separate pre-pasteurisation at 70 degrees C for 60 min as required by EEC regulation 1774/2002. The purpose of this study was to establish if, during pasteurisation and further processing and handling in full-scale BGPs, pathogens in biowaste could be sufficiently reduced to allow its use on arable land. Four BGPs were sampled on six occasions during 1 year. Sampling was performed from six locations during biogas production. The samples being analysed quantitatively to detect indicator bacteria (Escherichia coli, Enterococcus spp. and coliforms) and spore-forming bacteria (Clostridium spp. and Bacillus spp.) and qualitatively for bacterial pathogens (salmonella, listeria, campylobacter and VTEC O157). Salmonella was the most frequently isolated pathogen before pasteurisation In general, the treatment adequatly reduced both indicator and pathogenic bacteria. Spore-forming bacteria were not reduced. However, recontamination and regrowth of bacteria in biowaste was frequently noted after pasteurisation and digestion.

Animal Husbandry↗

PubMed2006

Site-related airborne biological hazard and seasonal variations in two wastewater treatment plants.

Results of a study conducted to assess the degree of airborne bacterial contamination generated by two wastewater treatment plants (WWTP) with different treatment systems and evaluate the dispersion of potential pathogens, have been described. Aerosols samples were collected in summer and winter with an agar impact sampler from several plant sites. External upwind and downwind controls were also examined. Total colony-forming counts of mesophilic and thermophilic bacteria, actinomycetes and streptomycetes, Gram-negatives, coliforms and sulfite-reducers were determined. Selective media were used in order to detect pathogenic bacteria. The lowest concentrations of mesophilic and thermophilic bacteria were 8 and 28 CFU/m(3) in plants A and B respectively, the highest >40,000 CFU/m(3) in both plants. Strains of Escherichia coli, Clostridium perfringens, Staphylococcus aureus and Enterococcus spp. were isolated in some sites of the two plants. Salmonella spp., Yersinia enterocolitica and Legionella spp. were never detected. The activities involving nebulization and mechanical aeration of wastewaters and the sewage inflows have proved to be of greatest potential risk. In both plants, we found a statistically significant dependence of bacterial contamination on the season for many of the analyzed parameters but a clear seasonal trend could not be observed.

Air↗

PubMed2001

Oxazolidinone antibiotics.

Many common gram-positive pathogens (eg, Staphylococcus aureus, Enterococcus spp, and Streptococcus pneumoniae) have become increasingly resistant to antimicrobial agents, and new drugs with activity against gram-positive bacteria are urgently needed. The oxazolidinones, a new chemical class of synthetic antimicrobial agent, have a unique mechanism of inhibiting bacterial protein synthesis. Linezolid, the first oxazolidinone to be approved for clinical use, displays in-vitro activity (generally bacteriostatic) against many important resistant pathogens, including meticillin-resistant Staph aureus, vancomycin-resistant enterococci, and penicillin-resistant Strep pneumoniae. Linezolid is a parenteral agent that also possesses near-complete oral bioavailability plus favourable pharmacokinetic and toxic effect profiles. Clinical trials confirm the activity of linezolid in the setting of pneumonia, skin and soft-tissue infections, and infections due to vancomycin-resistant enterococci. Linezolid shows promise as an alternative to glycopeptides and streptogramins to treat serious infections due to resistant gram-positive organisms. New agents with greater potency and new spectra of activity could arise from further modification of the oxazolidinone nucleus.

Acetamides↗

PubMed2005

Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP): prospective, randomised, controlled, double-blinded, multicentre trial.

BACKGROUND: Diabetic foot infections are a common and serious problem, yet few randomised trials of adequate quality have compared the efficacy of the various antibiotic regimens available for their treatment. Our aim was to assess the efficacy and safety of ertapenem versus piperacillin/tazobactam for foot infections. METHODS: We did a randomised, double-blinded, multicentre trial in adults (n=586) with diabetes and a foot infection classified as moderate-to-severe and requiring intravenous antibiotics. We assigned patients intravenous ertapenem (1 g daily; n=295) or piperacillin/tazobactam (3.375 g every 6 h; n=291) given for a minimum of 5 days, after which oral amoxicillin/clavulanic acid (875/125 mg every 12 h) could be given for up to 23 days. Investigators retained the option to administer vancomycin to patients in either group to ensure adequate coverage for potentially antibiotic resistant Enterococcus spp and meticillin-resistant Staphylococcus aureus (MRSA). Our primary outcome was the proportion of patients with a favourable clinical response (cure or improvement) on the day that intravenous antibiotic was discontinued. Analyses were by an evaluable-patient only approach. This study is registered with , number NCT00229112. FINDINGS: Of the 576 patients treated, 445 were available for assessment at the end of intravenous therapy. Both baseline characteristics and favourable clinical response rates were similar for the 226 who received ertapenem and the 219 who received piperacillin/tazobactam (94%vs 92%, respectively; between treatment difference 1.9%, 95% CI -2.9 to 6.9). Rates of favourable microbiological responses (eradication rates and clinical outcomes, by pathogen) and adverse events did not differ between groups. INTERPRETATION: Clinical and microbiological outcomes for patients treated with ertapenem were equivalent to those for patients treated with piperacillin/tazobactam, suggesting that this once-daily antibiotic should be considered for parenteral therapy of diabetic foot infections, when deemed appropriate.

Adult↗

PubMed2003

Susceptibility trends in bacteraemias: analyses of 7544 patient-unique bacteraemic episodes spanning 11 years (1990-2000).

The aim of the present study was to design more accurate tools for the selection of appropriate antimicrobial therapy for hospitalized patients with suspected sepsis. We created a large database comprising data on all patient-unique blood cultures obtained over an 11 year period (1 January, 1990 through 31 December, 2000). Improved statistical tools were applied to assess the trends in in vitro activity of individual antibiotic agents against various bacteria over time, and to calculate susceptibility rates of subsets of organisms. During the 11 year study period, 173571 blood cultures were obtained, of which 17703 (10.2%) were positive, with 7544 patient-unique blood cultures (4.3%). The mean annual number of positive, patient-unique cultures was 686 (standard deviation=79). The 10 most frequently isolated organisms were: Escherichia coli (1494), Staphylococcus aureus (1240), Klebsiella pneumoniae (779), Enterococcus spp. (631), Pseudomonas aeruginosa (488), Streptococcus pneumoniae (447), Enterobacter spp. (338), Acinetobacter spp. (298), Proteus mirabilis (260) and Candida spp. (254). No significant change was detected in the annual rates (means, standard deviations) per 1000 admissions of these organisms: the highest was E. coli (5.5, 1), the lowest was Candida (1, 0.3). Forty percent of organisms (N=2943) were obtained from patients in the emergency department (ED), 23% (1744) in medical departments, 15% (1134) in paediatric units, 13% (998) on surgical wards and 9% (709) in intensive care units (ICUs). Trend statistical analysis revealed a significant decrease in susceptibility in ED Enterobacteriaceae to eight of 15 (53%) tested antimicrobials, with a mean annual decrease of 1.6%+/-0.6%, in the ICU isolates, a significant decrease was detected in only five (33%) of the tested antimicrobials, with a mean annual decrease of 2.5%+/-1.3%. The difference in susceptibility between ED and ICU isolates was significant for all antimicrobials (P<0.001). A significant decrease in the susceptibility of E coli to nine of 15 drugs (60%) was detected, ranging from 0.7% to 2.7% annually. In K. pneumoniae a significant decrease in susceptibility of K. pneumoniae was detected with only two agents. Pseudomonas spp. isolates remained highly sensitive to all traditional anti-pseudomonal agents, without significant decay in sensitivity rates over time. Susceptibility of S. aureus to methicillin decreased significantly for several subsets of patients (P<0.001). Marked differences in susceptibility rates between the departments were detected. Trend statistical analyses, when appropriately applied to multi-year databases of microbial susceptibilities, may yield susceptibility tables that are significantly more accurate than traditional semi-annual or annual tables.

Anti-Bacterial Agents↗

PubMed2002

[Effectiveness of contact isolation in the control of multiresistant bacteria in an intensive care service].

AIM: To describe the frequency, characteristics and progression of critically ill patients admitted to the ICU, for whom isolation is indicated due to detection of multiresistant pathogenic bacteria, and to study the effectiveness of precautionary measures to avoid dissemination of these microorganisms. PATIENTS AND METHODS: Prospective, observational, cohort study performed by a specially created working group of four nurses and an ICU specialist. The study included 55 patients in whom contact isolation was indicated (isolation rate, 15.2 per 100 patients), collected over a 16-month period. RESULTS: The multiresistant bacteria responsible for isolation of the patients were: Pseudomonas aeruginosa (17 cases), Staphylococcus aureus (17 cases), Stenotrophomonas maltophilia (15 cases), Acinetobacter baumannii (4 cases) and extended-spectrum beta-lactamase (ESBL)- producing Enterobacteria (2 cases). Vancomycin-resistant Enterococcus spp. was not identified in any case. The mean duration of ICU isolation was 17.6 6 5.1 days (range 1-75). Multiresistant bacteria were classified as intra-ICU nosocomial in 39 cases (70.9%), extra-ICU nosocomial in 10 cases (18.2%) and community-acquired in 6 (10.9%). During the study period, no epidemic outbreak due to any of the controlled bacteria was detected. The multiresistant bacteria presented in the form of colonization in 41 cases (74.5%). The reasons for discontinuing isolation were death of the patient in 18 cases, transferal to a hospital ward (discharge from the ICU) in 19 cases, and eradication of the bacteria in 18 cases. Of the 55 patients with multiresistant bacteria, 35 (63.6%) died during hospitalization, and 23 of these (41.8%) during their stay in the ICU. CONCLUSIONS: The implementation of a working team for early detection of multiresistant pathogenic bacteria resulted in application of contact isolation in 15.2% of patients admitted. Surveillance to fulfill isolation precautions in a medical-surgical ICU achieved an absence of epidemic outbreaks due to these bacteria during the study period.

Aged↗

PubMed2001

Epidemiology and frequency of resistance among pathogens causing urinary tract infections in 1,510 hospitalized patients: a report from the SENTRY Antimicrobial Surveillance Program (North America).

Bacterial urinary tract infections (UTIs) are an important cause of septicemia resulting in high mortality rates, prolonged hospital stays and increased healthcare costs. Periodic reviews of pathogen frequency and susceptibility patterns impact on appropriate antimicrobial usage, leading to more effective prescribing practices. As part of the SENTRY Antimicrobial Surveillance Program (SENTRY, 1998), participants collected 50 consecutive UTI pathogens from patients hospitalized in 31 medical centers (26 in the United States and five in Canada) and forwarded subcultures to the coordinating center. Thirty-four antimicrobial agents were tested including two investigational compounds (quinupristin/dalfopristin [Q/D], gatifloxacin). The rank order of the 32 species identified during the study was: Escherichia coli (46.9%) > Enterococcus spp. (12.8%) > Klebsiella spp. (11.0%) > Pseudomonas aeruginosa (7.5%) > Proteus mirabilis (5.0%) > coagulase-negative staphylococci (CoNS; 3.4%). This pathogen rank order did not change from 1997 to 1998, but resistance patterns changed. Clonal spread of confirmed extended spectrum beta-lactamase-producing strains was not observed, but co-resistance was elevated for aminoglycosides, tetracyclines, sulfonamides, and fluoroquinolones. P. aeruginosa was most susceptible to amikacin (97.3%) > piperacillin +/- tazobactam (92.0-95.6%) > cefepime = imipenem (91.2%) > ceftazidime (85.8%). Fluoroquinolone resistance was greater in P. aeruginosa (24.8-39.8%) > P. mirabilis (5.3-13.3%) > Enterobacter spp. (6.7-8.9%) > Klebsiella spp. (4.2-7.8%) > E. coli (3.0-3.8%). Only 5% of enterococci were resistant to vancomycin. These results emphasize the need for continued surveillance studies for common infections which establish baseline resistance patterns by geographic areas, and have the potential to detect epidemics or direct local epidemiologic interventions.

Adolescent↗

PubMed2003

Occurrence and antimicrobial susceptibility patterns of pathogens isolated from skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 2000).

A total of 1,404 bacterial isolates were recovered from skin and soft tissue infections (SSTIs) from hospitalized patients in 24 sites in the United States (US) and 5 Canadian medical centers as part of the SENTRY Antimicrobial Surveillance Program. Isolates were collected between October and December, 2000. The rank order of pathogens was: Staphylococcus aureus (45.9%), Pseudomonas aeruginosa (10.8%), Enterococcus spp. (8.2%), Escherichia coli (7.0%), Enterobacter spp. (5.8%) and Klebsiella spp. (5.1%). The same order was observed in the US and Canada. Of note, almost 30% of S. aureus were oxacillin-resistant. Vancomycin resistance among enterococci was low (7.8%) representing a marked decrease from earlier SENTRY Program reports. Several antimicrobial agents remained very active against P. aeruginosa and Enterobacteriaceae isolates. In particular amikacin, cefepime, and the carbapenems (imipenem and meropenem) showed an excellent spectrum of activity (>95% susceptible). Extended-spectrum beta-lactamase production was observed in both E. coli (7.1%) and Klebsiella spp. (11.3%). Cefepime remained highly active, even against ceftazidime-resistant isolates of Enterobacter spp. The results of this study have identified the most common causes of SSTIs in hospitalized patients in North America, and can be used to make informed decisions concerning standards of empiric treatment for SSTIs in this region.

Anti-Bacterial Agents↗

PubMed1998

Reassessment of the incubation time in a controlled clinical comparison of the BacT/Alert aerobic FAN bottle and standard anaerobic bottle used aerobically for the detection of bloodstream infections.

This study assessed the minimum incubation time required to detect bloodstream infections during a controlled clinical comparison of the performance characteristics of the BacT/Alert aerobic FAN bottle and the standard anaerobic bottle used aerobically except on a selective basis. Blood was collected from adults with suspected bloodstream infections and inoculated into each bottle, which was monitored in the BacT/Alert Microbial Detection System. The anaerobic bottle was vented before incubation except when cultures were obtained from patients on the colorectal and gynecologic surgical and emergency services. Statistical analysis was limited to those culture sets in which each bottle was inoculated with > or = 8 mL of blood and bacterial growth was considered to be clinically significant. A total of 682 positive cultures from 243 patients satisfied the inclusion criteria. Significantly more isolates of Staphylococcus aureus (p < 0.001), S. epidermidis (p < 0.001), other coagulase-negative staphylococci (p < 0.001), Enterococcus spp. (p = 0.04), Escherichia coli (p = 0.03), all Enterobacteriaceae (p < 0.001), Pseudomonas aeruginosa (p = 0.001), and Candida spp. (p < 0.001) were detected by the aerobic FAN bottle. Significantly more septic episodes due to S. aureus, S. epidermidis, other coagulase-negative staphylococci, Enterobacteriaceae, P. aeruginosa, and Candida spp. were detected by the aerobic FAN bottle. Significantly more bacterial isolates were detected by the aerobic FAN whether or not antibiotics were being administered at the time of blood culture, whereas there were significantly fewer positive cultures in the vented standard anaerobic bottle when patients were receiving antimicrobial therapy than when they were not. All but 5% of positive cultures were detected within three days. Only six of the cultures requiring four or five days of incubation represented true misses, and only one of these six resulted in a change in therapy which, however, did not affect the patent's outcome.

Adult↗

PubMed1999

Characteristics of pathogens causing urinary tract infections in hospitals in North America: results from the SENTRY Antimicrobial Surveillance Program, 1997.

Urinary tract infection (UTI) is common and involves pathogens with changing susceptibility patterns. The SENTRY Antimicrobial Surveillance Program evaluates international pathogen incidence patterns to detect and manage the emergence of resistant strains. We describe the antimicrobial resistance patterns among 1617 pathogens recovered from UTIs during the third-quarter of 1997 in North America (United States and Canada), as part of this worldwide program. The isolates were tested against more than 50 antimicrobial agents (20 reported) by reference broth microdilution methods, and selected isolates were characterized by pulsed-field gel electrophoresis (PFGE) and automated ribotyping. The five most frequently isolated species were Escherichia coli (48.6%), Enterococcus spp. (13.7%), Klebsiella spp. (12.0%), Pseudomonas aeruginosa (6.2%), and Enterobacter spp. or Proteus mirabilis (3.8% each). For each nation, imipenem and cefepime produced the widest spectrum of coverage among the beta-lactams and amikacin was best among the aminoglycosides. For Gram-negative species, high resistance among beta-lactam antimicrobial agents was noted especially for various penicillins against E. coli (37.9% to 42.8%) and for the cephalosporins tested against enterococci (99.4% and 100%). Approximately 7.0% of enterococci in the USA were vancomycin-resistant (88% with Van A). P. aeruginosa provided the most consistent levels of resistance, but the following agents were most active against these organisms: amikacin (96.6 to 97.4% susceptible), tobramycin (89.5 to 100.0%), piperacillin/tazobactam (89.5 to 100.0%), piperacillin (89.5 to 96.6%), imipenem (89.7 to 92.1%), cefepime (77.6 to 89.7%), and ceftazidime (82.9 to 86.2%). E. coli (2.2 to 2.7%), K. pneumoniae (6.2 to 6.4%), and a single Enterobacter cloacae strain produced extended-spectrum beta-lactamases; and five other Enterobacter spp. were likely to have expressed chromosomally mediated (Amp C) Stably derepressed cephalosporinases with associated resistance to ceftazidime (16.7 to 21.2% resistance). These data demonstrated that several UTI isolates in SENTRY hospitals have high levels of resistance to various classes of antimicrobial agents with little evidence of clonal dissemination.

Anti-Bacterial Agents↗

PubMed1999

Disk diffusion susceptibility test development for the new glycylcycline, GAR-936.

The in vitro activity of GAR-936, a new semisynthetic glycylcycline, was evaluated in comparison with two tetracyclines and the disk diffusion susceptibility test was assessed. Nearly 700 recent clinical isolates were tested by reference broth microdilution and disk diffusion (two disk contents) methods. Among the Enterobacteriaceae, GAR-936 was generally two- to 16-fold more active than other tetracyclines. All enteric bacilli MIC90 results were < or = 4 micrograms/mL; the exception being Proteus mirabilis and indole-positive Proteae (> or = 8 micrograms/mL). GAR-936 demonstrated excellent activity against all Gram-positive cocci with Enterococcus spp. (including vancomycin-resistant isolates) inhibited at 0.25 microgram/mL (GAR-936 MIC90, 0.12 or 0.25 microgram/mL) and the oxacillin-resistant Staphylococcus aureus strains were inhibited at < or = 0.25 microgram/mL. GAR-936 demonstrated good potency against several non-fermentative bacteria, but possessed limited activity against Pseudomonas aeruginosa (MIC50, 8 micrograms/mL). In vitro susceptibility test methods were developed (disk diffusion versus reference MIC results) and tentative breakpoints were proposed. Using susceptibility criteria of either < or = 2 or < or = 4 micrograms/mL, GAR-936 in vitro susceptibility tests demonstrated rare significant serious inter-method discords (< or = 1.2%) and an absolute agreement between test results of 92.3 to 96.2%. These results indicate that GAR-936 has potent in vitro activity against a wide range of clinically important rapidly growing pathogenic bacteria, and that this novel glycylcycline candidate for clinical use should be further developed.

Anti-Bacterial Agents↗

PubMed2000

Antimicrobial activity and spectrum of the new glycylcycline, GAR-936 tested against 1,203 recent clinical bacterial isolates.

The in vitro activity of GAR-936, a new semisynthetic glycylcycline, was evaluated in comparison with two tetracyclines and several other antimicrobial agents. A total of 1,203 recent clinical isolates were tested by reference broth or agar dilution methods. Among the members of the family Enterobacteriaceae, GAR-936 was generally two- to four-fold more active than minocycline, and two- to 16-fold more active than tetracycline. All enteric bacilli MIC90 results were < or = 4 microg/mL; the exception being Proteus mirabilis and indole-positive Proteae (> or = 8 microg/mL). GAR-936 demonstrated excellent activity against all gram-positive cocci with 90% of the penicillin-resistant Streptococcus pneumoniae isolates inhibited at 0.03 microg/ml, while the same isolates had a MIC90 of 8 and > 8 microg/mL for minocycline and tetracycline, respectively. All Enterococcus spp., including vancomycin-resistant isolates, were inhibited at 0.25 microg/mL of GAR-936 (MIC90, 0.12 or 0.25 microg/mL). Although GAR-936 (MIC50, 0.25 microg/mL) was two-fold less active than minocycline (MIC50, 0.12 microg/mL) against oxacillin-resistant Staphylococcus aureus, all isolates were inhibited at < or = 0.25 microg/mL. GAR-936 demonstrated good activity against nonfermentative bacteria such as Acinetobacter spp. (MIC90, 2 microg/ml) and Stenotrophomonas maltophilia (MIC90, 4 microg/mL), but the compound exhibited only modest activity against Pseudomonas aeruginosa (MIC50, 8 microg/mL). Haemophilus influenzae (MIC90, 1-2 microg/mL), Moraxella catarrhalis (MIC90, 0.12 microg/mL), and various Neisseria spp. (MIC90, 0.12-0.5 microg/mL) were susceptible to GAR-936. These results indicate that GAR-936 has potent in vitro activity against a wide range of clinically important pathogenic bacteria, and that several gram-positive and -negative isolates resistant to older tetracyclines and other drug classes remain susceptible to GAR-936, the newest glycylcycline candidate for clinical use.

Anti-Bacterial Agents↗

PubMed2000

Antimicrobial and cancer cell growth inhibitory activities of 3beta-acetoxy-17beta-(L-prolyl)amino-5alpha-androstane in vitro.

The in vitro activity of the steroidal amide 3beta-acetoxy-17beta-(L-prolyl)amino-5alpha-androstane against 179 gram-positive clinical isolates was examined. The minimum bactericidal concentration (MBC)/MIC ratios were < or = 2 for 73% of methicillin-resistant Staphyllococcus aureus, 59% of vancomycin-resistant Enterococcus spp. and 88% of penicillin-resistant Streptococcus pneumoniae. The androstane derivative was bactericidal for a variety of other gram-positive genera, including Nocardia, Corynebacterium and Listeria. Variation in MICs is pH 6-8 media was slight. The frequency of occurrence of bacterial spontaneous mutations to resistance ranged from 10(-6) to 10(-9). Kill curve analysis confirmed the bactericidal nature of the steroidal amide, and demonstrated that killing was time dependent but not concentration dependent for all organisms. The ability of 3beta-acetoxy-17beta-(L-prolyl)amino-5alpha-androstane to inhibit human cancer cell growth was also evaluated. The concentration required to inhibit 50% of cell growth (GI50) was < 2.5 mg/l for all cell lines examined. In single-dose murine toxicity evaluations, the androstane derivative was non-toxic at doses up to 400 mg/kg.

Androstanes↗

PubMed2002

Moxifloxacin activity against clinical isolates compared with the activity of ciprofloxacin.

The activity of moxifloxacin, a new 8-methoxyquinolone, was compared in vitro with the activity of ciprofloxacin against clinical strains isolated from various sites of infection. The mode MIC values of moxifloxacin were superior to those of ciprofloxacin against Streptococcus pneumoniae, methicillin-susceptible and -resistant Staphylococcus aureus, Enterococcus spp., Escherichia coli and Acinetobacter spp., while ciprofloxacin was more active against Klebsiella pneumoniae and Pseudomonas spp. Both antibiotics had similar activity against Haemophilus influenzae, Moraxella catarrhalis and Enterobacter spp.

Anti-Infective Agents↗