Improved eradication of Clostridium difficile spores from toilets of hospitalized patients using an accelerated hydrogen peroxide as the cleaning agent.

BACKGROUND: C. difficle spores in the environment of patients with C. difficile associated disease (CDAD) are difficult to eliminate. Bleach (5000 ppm) has been advocated as an effective disinfectant for the environmental surfaces of patients with CDAD. Few alternatives to bleach for non-outbreak conditions have been evaluated in controlled healthcare studies. METHODS: This study was a prospective clinical comparison during non-outbreak conditions of the efficacy of an accelerated hydrogen peroxide cleaner (0.5% AHP) to the currently used stabilized hydrogen peroxide cleaner (0.05% SHP at manufacturer recommended use-dilution) with respect to spore removal from toilets in a tertiary care facility. The toilets used by patients who had diarrhea with and without C. difficile associated disease (CDAD) were cultured for C. difficile and were monitored using an ultraviolet mark (UVM) to assess cleaning compliance on a daily basis 5 days per week. A total of 243 patients and 714 samples were analysed. The culture results were included in the analysis only if the UVM audit from the same day confirmed that the toilet had been cleaned. RESULTS: Our data demonstrated that the efficacy of spore killing is formulation specific and cannot be generalized. The OxivirTB AHP formulation resulted in statistically significantly (p = 0.0023) lower levels of toxigenic C. difficile spores in toilets of patients with CDAD compared to the SHP formulation that was routinely being used (28% vs 45% culture positive). The background level of toxigenic C. difficile spores was 10% in toilets of patients with diarrhea not due to CDAD. The UVM audit indicated that despite the enhanced twice-daily cleaning protocol for CDAD patients cleaning was not achieved on approximately 30 - 40% of the days tested. CONCLUSION: Our data indicate that the AHP formulation evaluated that has some sporicidal activity was significantly better than the currently used SHP formulation. This AHP formulation provides a one-step process that significantly lowers the C. difficile spore level in toilets during non-outbreak conditions without the workplace safety concerns associated with 5000 ppm bleach.

Real-time PCR assay provides reliable assessment of intrapartum carriage of group B Streptococcus.

The objective of this study was to determine the reliability of the real-time PCR assay for determining the group B Streptococcus (GBS) status of women in labor. In this prospective study we compared the results of culture and PCR testing of vaginal and rectal samples collected by nursing staff when women were in labor. Patients' charts were also reviewed to obtain relevant information about pregnancy risk factors. Our results demonstrated a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 90.5%, 96.1%, 86.4%, and 97.4%, respectively, for rapid PCR. Of the 196 women evaluated, 29 (14.8%) presented with unknown GBS status, 11 (37.9%) of whom received unnecessary intrapartum antibiotics. The rapid real-time PCR test was robust and was able to reliably detect the presence of GBS in women in labor within 1 h of specimen submission to the laboratory. We recommend that the rapid PCR test be targeted to women who present in labor with unknown GBS status. In cases where the laboratory does not offer 24-h availability of testing, sample collection followed by PCR testing the next morning is still valuable and provides reliable results 24 to 48 h faster than culture and will aid appropriate decision-making regarding continuing or stopping antibiotics for neonates of women with unknown GBS status.

Reductions in workload and reporting time by use of methicillin-resistant Staphylococcus aureus screening with MRSASelect medium compared to mannitol-salt medium supplemented with oxacillin.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in both nosocomial and community settings, and screening for carriers is an important infection control practice in many hospitals. In this retrospective study, we demonstrate that the implementation of an MRSA screening protocol using a selective chromogenic medium (MRSASelect) reduced the workload for this screening test by 63.7% overall and by 12.6% per specimen and reduced the turnaround time for reporting by an average of 1.33 days for all MRSA screening specimens, 1.97 days for MRSA-positive specimens, and 1.3 days for MRSA-negative specimens compared to standard mannitol-salt agar supplemented with 6 mg of oxacillin/liter.

Antibiotic resistance in outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA).

The goal of the North American Urinary Tract Infection Collaborative Alliance (NAUTICA) study was to determine antibiotic susceptibility to commonly used agents for urinary tract infections against outpatient urinary isolates obtained in various geographic regions in the USA and Canada. Forty-one medical centres (30 from the USA and 11 from Canada) participated, with each centre submitting up to 50 consecutive outpatient midstream urine isolates. Isolates were identified to species level by the standard protocol of each laboratory. Susceptibility testing was determined using the National Committee for Clinical Laboratory Standards (NCCLS) microdilution method. Resistance breakpoints used were those published by the NCCLS, including: ampicillin (resistant > or = 32 microg/mL), sulphamethoxazole/trimethoprim (SMX/TMP) (resistant > or = 4 microg/mL), nitrofurantoin (resistant > or = 128 microg/mL), ciprofloxacin (resistant > or = 4 microg/mL) and levofloxacin (resistant > or = 8 microg/mL). Of the 1990 isolates collected, 75.1% (1494) were collected from the USA and 24.9% (496) were collected from Canada. The mean age of the patients was 48.3 years (range 1 month to 99 years), and 79.5% and 20.5% of isolates were obtained from women and men, respectively. The most common organisms were Escherichia coli (57.5%), Klebsiella pneumoniae (12.4%), Enterococcus spp. (6.6%), Proteus mirabilis (5.4%), Pseudomonas aeruginosa (2.9%), Citrobacter spp. (2.7%), Staphylococcus aureus (2.2%), Enterobacter cloacae (1.9%), coagulase-negative staphylococci (1.3%), Staphylococcus saprophyticus (1.2%), Klebsiella spp. (1.2%), Enterobacter aerogenes (1.1%) and Streptococcus agalactiae (1.0%). Among all 1990 isolates, 45.9% were resistant to ampicillin, 20.4% to SMX/TMP, 14.3% to nitrofurantoin, 9.7% to ciprofloxacin and 8.1% to levofloxacin. Fluoroquinolone resistance was highest in patients > or = 65 years of age. For the 1142 E. coli isolates, resistance rates were: ampicillin 37.7%, SMX/TMP 21.3%, ciprofloxacin 5.5%, levofloxacin 5.1% and nitrofurantoin 1.1%. For all 1990 isolates and for the 1142 E. coli only, resistance rates were significantly higher in US compared with Canadian medical centres. This study reports higher rates of antibiotic resistance in US versus Canadian outpatient urinary isolates and demonstrates the continuing evolution of resistance to antimicrobial agents.

Antibiotic combinations significantly more active than monotherapy in an in vitro infection model of Stenotrophomonas maltophilia.

The goal of this study was to investigate clinical doses of trimethoprim-sulfamethoxazole (TMP-SMX) alone and in combination against Stenotrophomonas maltophilia in an in vitro pharmacodynamic infection model. A 1-compartment model was established using 4 clinical isolates of S. maltophilia susceptible to TMP-SMX and susceptible or intermediately susceptible to at least one other agent (ie, ceftazidime, ciprofloxacin, gentamicin, tobramycin). Antibiotics alone and in combination were tested by simulating unbound serum concentration profiles achieved with multiple-dose regimens in humans. Despite susceptible minimum inhibitory concentrations, TMP-SMX alone was bacteriostatic at best against all isolates. All antibiotic combinations were more active than monotherapy as determined by bacterial reductions at both 24 and 48 h (P < 0.0001). Significant benefit was observed even with agents inactive alone or only intermediately susceptible based on minimum inhibitory concentrations. These preclinical data support further investigation of antibiotic combinations in the management of serious S. maltophilia infections.

Pharmacokinetics and pharmacodynamics of meropenem in febrile neutropenic patients with bacteremia.

BACKGROUND: Pharmacodynamic investigations with antimicrobials define the relationship between the infecting organism and achievable drug concentrations with clinical outcome. OBJECTIVE: To examine this relationship for meropenem in a population of patients who are at high risk of infection-related morbidity and mortality. METHODS: The study was a retrospective analysis of a multicenter, randomized, blinded clinical trial. A population-based predictive model was created using data from adults with febrile neutropenia and the nonparametric modeling program, NPEM. Patient age, body weight, and serum creatinine level were covariates in the model used to predict unbound concentrations for each patient. Pathogen susceptibility was estimated using product literature minimum inhibitory concentrations for effectiveness against 50% of microorganisms (MIC50) for specific organisms. The pharmacodynamic index of percent time above MIC (% T>MIC) was analyzed for its association with clinical outcome. RESULTS: A 2-compartment pharmacokinetic model using patient covariates of body weight and renal function best described the pharmacokinetics of meropenem in febrile neutropenic patients. Sixty patients with confirmed gram-positive or -negative bacteremia were studied. An average of 83% T>MIC was identified for the 42 clinical responders compared with 59% T>MIC for the 18 nonresponders (p = 0.04). An 80% clinical response rate was evident when the % T>MIC for meropenem exceeded 75% of the dosing interval (p = 0.01). CONCLUSIONS: To our knowledge, this is the first published report of a relationship between a pharmacodynamic index and clinical outcome in a febrile neutropenic population. Based on this relationship, dosing with intravenous meropenem 500 mg every 6 hours is predicted to be comparable to the currently recommended 1 g every 8 hours for serious infections. Our model provides further justification for a prospective clinical trial to evaluate a pharmacodynamically targeted meropenem dosing schedule as to its ability to improve clinical outcome in these patients.

Predictors of receipt of a fluoroquinolone versus trimethoprim-sulfamethoxazole for treatment of acute pyelonephritis in women in Manitoba, Canada.

PURPOSE: The increasing and comparatively high proportion of uropathogens in Canada resistant to trimethoprim-sulfamethoxazole (TMP-SMX) may be partially responsible for the increasing use of fluoroquinolones. A number of patient-specific variables have been identified as risk factors for infections caused by antibiotic-resistant pathogens. However, variables unrelated to need, have also been associated with receipt of broad-spectrum antibiotics. We identified patient variables associated with receipt of a fluoroquinolone versus TMP-SMX for treatment of acute pyelonephritis. METHODS: Healthcare claims from the province of Manitoba, Canada for the period February 1996 to March 1999 were examined to identify episodes of pyelonephritis in non-pregnant females between 18 and 65 years of age treated with TMP-SMX or a fluoroquinolone. Patient variables were identified based on healthcare claims review and data from Statistics Canada. Logistic regression was used to model the probability of receipt of a fluoroquinolone. RESULTS: A total of 1084 women met inclusion criteria; 653 treated with TMP-SMX and 431 treated with a fluoroquinolone. Age, income, rural residence, recent antibiotic use, recent hospitalization and presentation to an emergency room (ER) were positively associated with receipt of a fluoroquinolone. CONCLUSIONS: Patient variables reportedly associated with an increased probability of resistant organisms (e.g., age, recent antibiotic use and recent hospitalization) were significantly associated with an increased probability of receipt of fluoroquinolones. However, variables unrelated to antibiotic resistance (e.g., income, rural residence and presentation to an ER) were also significantly associated with receipt of a fluoroquinolone.

Effect of antibiotic sequence on combination regimens against Pseudomonas aeruginosa in a multiple-dose, in vitro infection model.

The goal of this study was to investigate the effect of antibiotic sequence on combination regimens against Pseudomonas aeruginosa in an in vitro infection model. Ceftazidime plus ciprofloxacin and ceftazidime plus tobramycin were dosed every 12 h for 48 h using simultaneous or staggered administration. Simultaneous dosing and ceftazidime followed by ciprofloxacin or tobramycin were significantly more active at both 24 h (p = 0.03) and 48 h (p < 0.0001) than ciprofloxacin or tobramycin followed by ceftazidime. Final bacterial kill was sixfold greater with the former regimens. This study showed that antibiotic sequence had a significant and class dependent effect on antibacterial response. The clinical relevance of these observations warrants further investigations in animal models.

Peritoneal fluid titer test for peritoneal dialysis-related peritonitis.

Standard microbiological tests (i.e., MIC) do not account for the unique factors of peritoneal dialysis (PD)-related peritonitis which can significantly influence treatment response. Our goals were to develop a peritoneal fluid titer (PFT) test and to conduct a pilot study of its association with clinical outcome. The methodology was developed by using spent dialysate collected from patients with bacterial PD-related peritonitis prior to the initiation of antibiotics. Dialysate was processed and spiked with antibiotic to simulate two standard intraperitoneal regimens: cefazolin plus tobramycin and cefazolin alone. Thirty-six clinical isolates, including Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa, were tested. In the pilot study, dialysate was collected from 14 patients with bacterial PD-related peritonitis. Titers were determined by using each patient's dialysate and infecting pathogen. Titers were highly reproducible, with discrepancies in only 1% of cases. Overall, PFTs were notably higher against gram-positive bacteria (P < 0.0001). The addition of tobramycin increased titers significantly from zero to values of 1/16 to 1/64 against E. cloacae and P. aeruginosa (P < 0.0001). In the pilot study, peritoneal fluid inhibitory titers were significantly associated with clinical outcome, with a median value of 1/96 for patients who were cured compared to 1/32 for those who failed treatment (P = 0.036). In conclusion, this study provides preliminary support for the PFT as a pharmacodynamic index specific to the treatment of PD-related peritonitis. With further characterization and validation in patients, the PFT test may advance the study of antibiotic therapies for PD-related peritonitis.

Treatment and outcome of Pseudomonas aeruginosa bacteraemia: an antibiotic pharmacodynamic analysis.

OBJECTIVES: To conduct a retrospective study of antibiotic pharmacodynamics in the treatment of Pseudomonas aeruginosa bacteraemia, and to identify pharmacodynamic indices associated with clinical cure. METHODS: Cases of P. aeruginosa bacteraemia were identified, and information related to patient demographics, clinical status, antibiotic treatment and clinical outcome were documented. Anti-pseudomonal therapy was assessed, and concentration versus time profiles were constructed using measured levels for aminoglycosides, or population pharmacokinetic models for other antibiotics. P. aeruginosa isolates from all patients were retrieved and MICs for the anti-pseudomonal agents used to treat the episode of bacteraemia were determined. Patient- and treatment-related factors were tested for associations with clinical outcome using univariate and multivariate analyses. RESULTS: Fifty cases of P. aeruginosa bacteraemia were identified and 38 cases were included in the pharmacodynamic analysis. Eighty-seven percent of patients received an aminoglycoside or ciprofloxacin and 79% received piperacillin or ceftazidime. A majority of patients, 71%, were administered a combination of antibiotics. Treatment outcomes were documented as persistent infection in 21%, death within 2-30 days in 21% and clinical cure in 58% of cases. Peak/MIC (P=0.001) and AUC24/MIC (P=0.002) for aminoglycosides and ciprofloxacin were significant factors in univariate tests. Only peak/MIC was associated independently with treatment outcome (P=0.017) in logistic regression analysis. The predicted probability of cure was > or =90% when peak/MIC was at least 8. CONCLUSION: Pharmacodynamic considerations including aggressive dosing with targeted peak/MICs for aminoglycosides and ciprofloxacin are strongly associated with clinical outcome and essential to the appropriate management of P. aeruginosa bacteraemia.

AUC(0-t)/MIC is a continuous index of fluoroquinolone exposure and predictive of antibacterial response for Streptococcus pneumoniae in an in vitro infection model.

OBJECTIVE: To conduct a comprehensive pharmacodynamic analysis of moxifloxacin and levofloxacin against Streptococcus pneumoniae in an in vitro infection model. METHODS: In dose escalation studies, single doses with peak concentrations equivalent to 1 x, 2 x, 4 x, 8 x, 16 x and 32 x MIC against two isolates of S. pneumoniae were studied over 24 h. Traditional pharmacodynamic indices, including peak concentration divided by MIC (peak/MIC), time of concentration above MIC (T > MIC) and AUC24/MIC, were estimated for all regimens. As a continuous index of fluoroquinolone exposure, AUC0-t/MIC was also calculated, as AUC from time 0 to 1, 2 and 6 h divided by MIC. Correlations between pharmacodynamic indices and antibacterial effects were examined using linear and non-linear methods. In validation experiments, the pharmacodynamic model was used to predict bacterial kill curves, produced by simulated clinical doses of moxifloxacin and levofloxacin against two other S. pneumoniae isolates. RESULTS: Peak/MIC was most predictive of early bacterial kill, whereas T > MIC was significantly associated with final bacterial counts at 24 h. Antibacterial effects were bacteriostatic when T > MIC was 48% and bactericidal when values exceeded 55%. AUC0-t/MIC was strongly associated with bacterial kill throughout the dosing interval. Bactericidal activity and bacterial eradication were associated with AUC0-t/MICs of 28 and 135, respectively. AUC0-t/MIC was also highly predictive of bacterial kill curves produced by simulated clinical doses of moxifloxacin and levofloxacin (precision 0.36 log10 cfu/mL, bias 0.02 log10 cfu/mL). CONCLUSION: This study demonstrated the novel application of AUC0-t/MIC as a continuous index of antibiotic activity, and provided extensive characterization of fluoroquinolone pharmacodynamics against S. pneumoniae.

Antimicrobial treatment in diabetic women with asymptomatic bacteriuria.

BACKGROUND: Asymptomatic bacteriuria is common among women with diabetes, and the treatment of such infections has been recommended to prevent complications related to symptomatic urinary tract infection. METHODS: We enrolled women (>16 years of age) with diabetes, bacteriuria (> or =105 colony-forming units of an organism per milliliter in cultures of two consecutive urine specimens), and no urinary symptoms; 50 were randomly assigned to receive placebo and 55 to receive antimicrobial therapy. For the first six weeks, which included the initial course of treatment, the study was placebo-controlled and double-blind. Subsequently, the women were screened for bacteriuria every three months for up to three years; antimicrobial therapy was provided to women in the antimicrobial-therapy group who had asymptomatic bacteriuria. RESULTS: Four weeks after the end of the initial course of therapy, 78 percent of placebo recipients had bacteriuria, as compared with 20 percent of women who received antimicrobial agents (P<0.001). During a mean follow-up of 27 months, 20 of 50 women in the placebo group (40 percent) and 23 of 55 women in the antimicrobial-therapy group (42 percent) had at least one episode of symptomatic urinary tract infection. The time to a first symptomatic episode was similar in the placebo group and the antimicrobial-therapy group (P=0.67 by the log-rank test), as were the (+/-SD) rates of any symptomatic urinary tract infection (1.10+/-0.17 and 0.93+/-0.14 per 1000 days of follow-up, respectively; relative risk, 1.19; 95 percent confidence interval, 0.28 to 1.81), pyelonephritis (0.28+/-0.08 and 0.13+/-0.05 per 1000 days of follow-up; relative risk, 2.13; 95 percent confidence interval, 0.81 to 5.62), and hospitalization for urinary tract infection (0.10+/-0.36 and 0.06+/-0.22 per 1000 days of follow-up; relative risk, 1.93; 95 percent confidence interval, 0.47 to 7.89). The women in the antimicrobial-therapy group had almost five times as many days of antibiotic use for urinary tract infection as did the women in the placebo group (158.2+/-1.7 vs. 33.7+/-0.91 per 1000 days of follow-up; relative risk, 0.21; 95 percent confidence interval, 0.20 to 0.22). CONCLUSIONS: Treatment of asymptomatic bacteriuria in women with diabetes does not appear to reduce complications. Diabetes itself should not be an indication for screening for or treatment of asymptomatic bacteriuria.

Challenging the current treatment paradigm for methicillin-resistant Staphylococcus epidermidis peritonitis in peritoneal dialysis patients.

OBJECTIVES: To analyze clinical outcomes of Staphylococcus epidermidis peritoneal dialysis peritonitis before and after an interventional switch from a vancomycin/ tobramycin to a cefazolin/tobramycin regimen for empiric treatment. To examine risk factors associated with clinical failure. DESIGN: A retrospective study. SETTING: A peritoneal dialysis program within a university-affiliated tertiary-care hospital. PATIENTS: 93 episodes of S. epidermidis peritonitis over a 6-year period. INTERVENTIONS: Clinical responses were compared between treatments using chi-square or Fisher's exact test. Univariate and multivariate analyses were used to identify significant risk factors for clinical failure. MEASUREMENTS AND MAIN RESULTS: There was no difference in the overall response rates observed with vancomycin (40/49; 81.6%) and cefazolin (23/29; 79.3%) regimens for episodes of S. epidermidis peritonitis. Furthermore, the presence of methicillin resistance in 63 of 93 cases (67.7%) had no influence on clinical outcome, with response rates of 83.9% (26/31) and 82.4% (14/17) for empiric vancomycin and cefazolin regimens, respectively. Tobramycin therapy of less than 2 days was an independent risk factor for clinical failure in multivariate logistic regression analysis (odds ratio 4.44, 95% confidence interval 1.28 - 15.48; p = 0.02). CONCLUSIONS: Empiric treatment with intraperitoneal cefazolin was as effective as vancomycin for S. epiderimidis peritonitis despite a high prevalence of methicillin resistance. Tobramycin therapy of less than 2 days was strongly associated with treatment failure.

Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy.

The objective of this study was to characterize the relationship between gentamicin concentrations during surgery and the development of wound infection following colorectal operations. Despite decades of research in surgical prophylaxis, the relationship between intraoperative antibiotic concentrations and postoperative infection and the concentrations required for effective prophylaxis have not been established. A pharmacodynamic analysis was conducted using data from a previous prospective, randomized, double-blind clinical study which compared two dosage regimens of gentamicin plus metronidazole for prophylaxis in connection with elective colorectal surgery. Univariate and multivariate analyses of risk factors for postoperative wound infection were conducted, and the relationship between intraoperative gentamicin concentrations and surgical outcome was characterized. The gentamicin concentration at the time of surgical closure was one of the strongest independent risk factors for infection (P = 0.02), along with the presence of diabetes mellitus (P = 0.02), stoma (P = 0.04), and advanced age (P = 0.05). Gentamicin concentrations at closure of less than 0.5 mg/liter were associated with an infection rate of 80% (representing 8 of 10 patients with concentrations below that level) (P = 0.003). Receiver operating characteristic curve analysis identified a critical closure concentration of 1.6 mg/liter for effective surgical prophylaxis (P = 0.002; sensitivity, 70.8%; specificity, 65.9%). This study provides new and important information on antibiotic pharmacodynamics in surgical prophylaxis. It demonstrates the critical effect of the antibiotic concentration at closure on wound infection and suggests a significant association between the concentration and other well-established risk factors, like the timing of preoperative antibiotic administration and surgery duration.

An outbreak of necrotizing enterocolitis associated with a novel clostridium species in a neonatal intensive care unit.

An outbreak of necrotizing enterocolitis (NEC) occurred in 6 neonates within a 2-month period. Blood cultures from 3 of these neonates grew the same strain of what appears to be a novel clostridial species for which the name "Clostridium neonatale" has been proposed. A point-prevalence survey that used rectal swabs was performed in our intensive-care and intermediate-care nurseries, and it indicated that 20.8% of neonates carried this same "C. neonatale" strain despite having no evidence of NEC. In conclusion, we describe an outbreak of NEC associated with the novel species, and we suggest that, in larger neonates, carriage of this type of Clostridium species may be a necessary step in the multistage pathogenesis of NEC.

Activities of new fluoroquinolones, ketolides, and other antimicrobials against blood culture isolates of viridans group streptococci from across Canada, 2000.

The rates of nonsusceptibility to penicillin, erythromycin, and clindamycin of 191 blood culture isolates of viridans group streptococci collected from across Canada in 2000 were 36, 42, and 10%, respectively. Although 8% of the strains were resistant to ciprofloxacin (MIC >or= 4 microg/ml), the MICs of gemifloxacin, BMS 284756, telithromycin, and ABT 773 at which 90% of the strains were inhibited were 0.06, 0.06, 0.12, and 0.03 microg/ml, respectively.