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.

Long-term Escherichia coli asymptomatic bacteriuria among women with diabetes mellitus.

BACKGROUND: Persistent Escherichia coli asymptomatic bacteriuria (ASB) is common among persons with diabetes mellitus, but the duration of colonization and the rates of recolonization are unknown. We estimated the duration of colonization and the rate of recolonization among successively isolated E. coli from diabetic women with ASB and compared the virulence profiles with uropathogenic and commensal E. coli. METHODS: A total of 105 women with diabetes were enrolled in a randomized, controlled clinical trial for treatment of ASB in Manitoba, Canada, and were observed at least every 3 months for up to 3 years. We analyzed 517 isolates from 70 women with repeated E. coli ASB for genetic similarity using enterobacterial repetitive intergenic consensus polymerase chain reaction. Unique strains were screened for uropathogenic virulence characteristics using dot blot hybridization and compared with different collections of E. coli isolates. RESULTS: On average, differences were found among women assigned to treatment for ASB, those treated only for symptomatic infections, and untreated women in (1) follow-up time with bacteriuria (29%, 31%, and 66%, respectively; P<.001), (2) duration of bacteriuria (2.2, 2.5, and 3.7 months, respectively; P=.04), and (3) carriage of unique isolates (2.4, 2.8, and 4 months, respectively; P=.03). Women assigned to antibiotic treatment usually had recurrent infection (76%), 64% of the time with a genetically new E. coli strain. Virulence characteristics of these isolates were comparable to those of fecal isolates from healthy women. CONCLUSIONS: Treatment may reduce the overall proportion of time infected in the long term and carriage of a unique strain, but most treatment regimens were followed by subsequent recolonization. Infecting strains did not have virulence factors characteristic of uropathogenic E. coli.

UV-visible marker confirms that environmental persistence of Clostridium difficile spores in toilets of patients with C. difficile-associated diarrhea is associated with lack of compliance with cleaning protocol.e.

BACKGROUND: An ultraviolet visible marker (UVM) was used to assess the cleaning compliance of housekeeping staff for toilets in a tertiary healthcare setting. METHODS: The UVM was applied to the toilets of patients who were on isolation precautions due to Clostridium difficile-associated diarrhea (CDAD) as well as for patients who were not on isolation precautions. Cleaning was visually scored using a numeric system where 0, 1, 2, and 3 represented; no, light, moderate or heavy residual UVM. Rodac plates containing CDMN selective agar were used to test for the presence of C. difficile on the surfaces of patient's toilets. RESULTS: Despite twice daily cleaning for the toilets of patients who were on CDAD isolation precautions, the average cleaning score was 1.23 whereas the average cleaning score for toilets of patients not on isolation precautions was 0.9. Even with optimal cleaning (UVM score of 0) C. difficile was detected from 33% of the samples taken from toilets of patients with CDAD (4% detection in toilet samples from patients who had diarrhea not due to CDAD). CONCLUSION: Our data demonstrated the value of UVM for monitoring the compliance of housekeeping staff with the facility's toilet cleaning protocol. In addition to providing good physical cleaning action, agents with some sporicidal activity against C. difficile may be needed to effectively reduce the environmental reservoir.

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.

Pharmacokinetics/pharmacodynamics of levofloxacin 750 mg once daily in young women with acute uncomplicated pyelonephritis.

This pilot study was undertaken to characterise the pharmacokinetics, pharmacodynamics and potential clinical efficacy of levofloxacin 750 mg once daily for 5 days for treatment of women with acute uncomplicated pyelonephritis. Four women diagnosed with acute pyelonephritis were enrolled. Following pre-therapy specimen collection, an initial oral dose of 750 mg levofloxacin was administered. The mean pharmacokinetic parameters for the first dose were: maximum serum concentration (C(max)) 12.5+/-4.7 mg/L (range 5.6-16.0mg/L) (fC(max) 8.8+/-3.3, where f indicates the levofloxacin free or non-protein-bound fraction), area under the serum concentration-time curve (AUC) 85.4+/-14.1 mgh/L (range 66.2-96.8 mgh/L) (fAUC 59.8+/-9.9) and serum half-life (t(1/2)) 6.7+/-0.5h. Mean urine concentrations were 88.0+/-100mg/L at the 0-3 h collection, 307+/-143 mg/L at 3-6 h, 170+/-107 mg/L at 6-12 h and 85+/-8 mg/L at 12-24 h. Mean levofloxacin serum pharmacodynamics for infecting Escherichia coli were: C(max)/minimum inhibitory concentration (MIC) 323+/-185(fC(max)/MIC 226+/-129); and AUC/MIC 2339+/-830(fAUC/MIC 1647+/-579). Mean urine levofloxacin concentration/MIC ratios were: 900+/-1389 for 0-3 h, 12100+/-4950 for 3-6 h, 5922+/-3912 for 6-12 h and 2233+/-1037 for 12-24 h. Levofloxacin eradicated E. coli from the urine by 3-6 h after the first dose. Levofloxacin 750 mg once daily for 5 days has pharmacodynamics that support further evaluation of this regimen for treatment of women with acute uncomplicated pyelonephritis.

Acanthamoeba species Keratitis in a Soft Contact Lens Wearer Molecularly Linked to Well Water.

Acanthamoeba species keratitis has been associated with soft contact lens wear. In the present report, an epidemiological link was established between the patient's isolate and well water from the home using molecular methods. To the authors' knowledge, this is the first case in Canada where such a link has been established. Primary care practitioners and specialists, including ophthalmologists and infectious diseases specialists, must maintain a high degree of clinical suspicion in soft contact lens wearers with keratitis unresponsive to conventional topical and systemic treatment.

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.

Evaluating ciprofloxacin dosing for Pseudomonas aeruginosa infection by using clinical outcome-based Monte Carlo simulations.

Pseudomonas aeruginosa causes serious infections whose outcome is highly dependent on antimicrobial therapy. The goal of this study was to predict the relative efficacies of three ciprofloxacin dosing regimens for P. aeruginosa infection using clinical outcome-based Monte Carlo simulations (MCS) with "real patient" demographics, pharmacokinetics, MICs, and pharmacodynamics (PDs). Each cohort consisted of 1,000 simulated study subjects. Three ciprofloxacin dosing regimens were studied, including (i) the recommended standard dose of 400 mg given intravenously (i.v.) every 12 h (q12h), (ii) the recommended high dose of 400 mg i.v. q8h, and (iii) a novel, PD-targeted regimen to attain a fAUC/MIC value of >86. Probability of target attainment (PTA) and probability of cure (POC) were determined for each regimen. POC with the standard dose was at least 0.90 if pathogen MICs were < or =0.25 microg/ml but only 0.59 or 0.27 if MICs were 0.5 or 1 microg/ml, respectively. Predicted cure rates in these MIC categories were significantly higher at 0.72 and 0.40 with the high dose and 0.91 and 0.72 with the PD-targeted regimen(P < 0.0001). Analyses based on the local susceptibility profile produced PTA and POC estimates of 0.44 and 0.74 with the standard ciprofloxacin dose, 0.58 and 0.81 with the high dose, and 0.84 and 0.93 with the PD-targeted regimen, respectively. In conclusion, as demonstrated by clinical outcome-based MCSs, the highest recommended ciprofloxacin dose of 400 mg i.v. q8h should be used in the treatment of P. aeruginosa infection to improve PD target attainment and clinical cure. However, even this appears ineffective if pathogen MICs are 1 mug/ml, warranting the consideration of a lower MIC breakpoint, < or =0.5 microg/ml.

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.

A prospective, randomized trial of 3 or 14 days of ciprofloxacin treatment for acute urinary tract infection in patients with spinal cord injury.

BACKGROUND: Urinary tract infection (UTI) is common among patients with spinal cord injury. The optimal duration of treatment for symptomatic UTI has not been determined. METHODS: A randomized, double-blind, placebo-controlled trial compared 3-day and 14-day regimens of ciprofloxacin, 250 mg twice daily, for the treatment of acute UTI in patients with spinal cord injury. Patients with pyelonephritis, struvite stones, hydronephrosis, or long-term indwelling catheters were excluded from the trial. RESULTS: Sixty patients with spinal cord injury were enrolled in the trial, with 30 patients assigned to each study arm. The most common infecting organisms were Klebsiella species (30%), Enterococcus species (22%), and Escherichia coli (22%); 33% of the infections were polymicrobial. Microbiological cure at long-term follow-up was significantly better among patients who received therapy for 14 days than among patients who received therapy for 3 days. By 6 weeks of follow-up, microbiological relapse (in 11 [37%] of 30 patients vs. 2 [7%] of 30 patients; 95% confidence interval [CI], 1.38-3.18; P=.01) and symptomatic relapse (in 7 [23%] 30 patients vs. 0 of 30 patients; 95% CI, 1.69-3.13; P=.01) both occurred more frequently in patients treated for 3 days. Reinfection occurred with similar frequency in patients in the 2 study arms. Six of 7 evaluable patients with treatment failure had a fluoroquinolone-resistant organism isolated at enrollment. CONCLUSIONS: For patients with spinal cord injury, treatment of acute symptomatic UTI for 14 days leads to improved clinical and microbiological outcomes, compared with short-course therapy.

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.