Infective endocarditis of a native aortic valve due to Pseudomonas aeruginosa complicated by progressive multi-drug resistance.

BACKGROUND: Treatment of infective endocarditis secondary to Pseudomonas aeruginosa can be challenging because of this organism's ability to acquire antimicrobial resistance over time. METHODS: We describe a patient with native aortic valve infective endocarditis due to P. aeruginosa who developed progressive multi-drug resistance while on therapy. The resistance mechanisms were characterized using whole-genome sequencing. RESULTS: We identified two mutations in subsequent isolates (dacB and OprD) that conferred resistance to anti-pseudomonal penicillins, cephalosporins, and carbapenems. The patient was treated with combination high-dose continuous infusion meropenem and ciprofloxacin therapy, in addition to bioprosthetic aortic valve replacement and repair of ventricular septal wall defect. Antibiotics were continued for 6 weeks post-cardiac surgery and the patient remains infection free 18 months post-completion of antibiotic therapy. CONCLUSION: Clinicians should be aware of the ability of P. aeruginosa to acquire resistance mechanisms in response to selective antibiotic pressures in high-inoculum infections such as infective endocarditis. The mutations identified in this case report correlated well with the evolving antimicrobial resistance profile observed.

HISTORIQUE: Il peut être difficile de traiter une endocardite infectieuse causée par un Pseudomonas aeruginosa en raison de la capacité de cet organisme à acquérir une résistance aux antimicrobiens. MÉTHODOLOGIE: Les chercheurs décrivent un patient atteint d'une endocardite infectieuse de la valve aortique d'origine, attribuable à un P. aeruginosa, qui a acquis une multirésistance progressive pendant son traitement. Le mécanisme de résistance était caractérisé par le séquençage du génome entier. RÉSULTATS: Les auteurs ont dépisté deux mutations dans les isolats subséquents (dacB et OprD ), responsables d'une résistance aux pénicillines, aux céphalosporines et aux carbapénèmes antipseudomonaux. Le patient a reçu une polythérapie de perfusion continue de méropénem à forte dose et de ciprofloxacine, en plus du remplacement d'une valve aortique bioprothétique et de la réparation d'une communication interventriculaire. L'antibiothérapie s'est poursuivie six semaines après l'opération, et le patient n'avait pas d'infection 18 mois après la fin de l'antibiothérapie. CONCLUSION: Les cliniciens devraient savoir que le P. aeruginosa peut acquérir des mécanismes de résistance en réponse aux pressions antibiotiques sélectives en cas d'infections comportant un titre élevé d'inoculum comme une endocardite infectieuse. Les mutations constatées dans le présent rapport de cas étaient bien corrélées avec l'évolution du profil de résistance antimicrobienne observé.

Retrospective multicentre matched cohort study comparing safety and efficacy outcomes of intermittent-infusion versus continuous-infusion vancomycin.

BACKGROUND: Patients with good renal function receiving intermittent-infusion vancomycin (IIV) may require total daily doses ≥4 g to achieve trough concentrations of 15-20 mg/L, increasing the risk of vancomycin-associated nephrotoxicity. Continuous-infusion vancomycin (CIV) may be associated with a lower risk of vancomycin-associated nephrotoxicity compared with IIV, but studies comparing safety of both dosing strategies are lacking. OBJECTIVES: To compare the risk of nephrotoxicity with CIV versus IIV when target concentration ranges were the same with both dosing modalities. METHODS: A retrospective multicentre matched cohort study of admitted patients between 1 January 2010 and 31 December 2016 was completed. Adult patients who received ≥48 h of vancomycin with at least one steady-state vancomycin concentration were eligible. The primary outcome was to compare the rates of nephrotoxic risk and renal injury, defined by the RIFLE criteria, between CIV and IIV. RESULTS: Of 2136 patients who received vancomycin during the study period, 146 CIV patients were eligible and matched to 146 IIV patients. After adjustment of potential confounders, CIV was found to have a lower odds of developing nephrotoxic risk (OR 0.42, 95% CI 0.21-0.98, P = 0.025) and renal injury (OR 0.19, 95% CI 0.05-0.59, P = 0.004). CONCLUSIONS: CIV is associated with a lower odds of nephrotoxicity compared with IIV when targeting the same concentration range and should be an alternative dosing strategy for patients who will receive prolonged therapy or require >4 g/day to achieve therapeutic levels.

Development and validation of a screening tool for early identification of bloodstream infection in older patients - a retrospective case-control study.

BACKGROUND: Delayed diagnosis of bloodstream infection (BSI) occurs in > 20% of older patients, with misdiagnosis in 35%. Our objective was to develop and validate a clinically useful screening tool to identify older patients with a high probability of having a BSI. METHODS: Hospitalized patients > 80 years old with BSI (n = 105/group) were evaluated for the tool development in this retrospective matched case-controlled study (learn cohort). The tool was validated in different retrospectively matched case and control patients > 80 years old (n = 120/group) and 65 to 79 years old (n = 250/group) (test cohort). Binary logistic regression was used to develop a screening tool using laboratory and clinical parameters that were significantly associated with BSI (P < 0.05; adjusted odds ratio (OR) > 1); and Classification and Regression Tree (CART) analysis was used to identify parameter breakpoints. Performance metrics were used to evaluate and validate the tool. RESULTS: The significant parameters associated with BSI were maximum temperature (Tmax)(> 37.55C)(OR = 42.575), neutrophils (> 7.95)(OR = 1.923), a change in level of consciousness (LOC) (Yes = 1, No = 0)(OR = 1.571), blood urea nitrogen (BUN)(> 10.05)(OR = 1.359), glucose (> 7.35)(OR = 1.167), albumin (< 33.5)(OR = 1.038) and alanine aminotransferase (ALT) (> 19.5)(OR = 1.005). The optimal screening tool [Ln (odds of BSI) = - 150.299 + 3.751(Tmax) + 0.654(neutrophils) + 0.452(change in LOC) + 0.307(BUN) + 0.154(glucose) + 0.038(albumin) + 0.005(ALT)] had favorable performance metrics in the learn and test cohorts (sensitivity, specificity and accuracy of 95% in the learn cohort and 77, 89, and 81% in the total test cohort); and performed better than using only temperature and neutrophil count. CONCLUSIONS: The validated tool had high predictive value which may improve early identification and management of BSI in older patients.

Voriconazole prophylaxis in leukemic patients: A retrospective single-center study.

BACKGROUND: Invasive fungal infections commonly occur in acute myeloid and lymphoblastic leukemia patients receiving chemotherapy. In these patients with acute leukemia, posaconazole prophylaxis is recommended; however, voriconazole may be a less costly alternative. OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of voriconazole prophylaxis in acute leukemia patients. METHODS: A retrospective chart review of inpatients at Sunnybrook Health Sciences Centre between 2005 and 2017 was completed. Hospitalized adult acute leukemia patients who received voriconazole prophylaxis (cases) were compared to patients who received fluconazole or no prophylaxis during chemotherapy (controls). Statistical analyses comparing baseline characteristics, safety, and efficacy outcomes between the study cohorts were completed. A posaconazole literature-based weighted mean risk was compared to the voriconazole risk of invasive fungal infection identified in this study. RESULTS: Of 490 acute myeloid leukemia or acute lymphoblastic leukemia patients, 83 controls and 92 cases were eligible. Case patients received an average of 24.4 ± 10.8 days of voriconazole prophylaxis. The incidence of proven or probable invasive fungal infections with voriconazole was 3.3% (3/92) versus 7.2% (6/83) in the control cohort (p > 0.05) and was comparable to the literature reported weighted incidence of invasive fungal infection with posaconazole (2.4 ± 2.1%; 95% CI 1.3%-3.4%; p > 0.05). Voriconazole was well tolerated by patients (91%; 84/91; seven discontinued due to asymptomatic elevated liver function tests). CONCLUSIONS: Voriconazole prophylaxis was found to be safe, effective, and comparable to literature-based efficacy data for risk of invasive fungal infection with posaconazole antifungal prophylaxis in patients with acute leukemia undergoing chemotherapy and could represent a significant cost advantage.

Fluoroquinolone Antibiotic Prophylaxis to Prevent Post-Traumatic Bacterial Infectious Endophthalmitis: Using Monte Carlo Simulation to Evaluate the Probability of Success.

Purpose: Patients with open globe injuries routinely receive fluoroquinolone (FQ) prophylaxis to prevent bacterial infectious endophthalmitis. Owing to the rarity of this infection, there is an absence of clinical trials evaluating optimal prophylactic FQ dosing. To address this knowledge gap, we conducted a Monte Carlo simulation (MCS)-based study to identify the FQ dosing option(s) that optimize pharmacokinetic-pharmacodynamic FQ target attainment against common bacterial pathogens implicated in post-traumatic bacterial infectious endophthalmitis (PTBIE). Methods: Weighted mean pharmacokinetic parameters and standard deviations for ciprofloxacin, levofloxacin, and moxifloxacin were calculated from published studies in healthy volunteers. The incidence and FQ susceptibility profiles for the most common bacteria causing PTBIE were extracted from the literature. MCS was used to determine the cumulative fraction of response (CFR) for 5 FQ dosing options to determine the probability of attaining pathogen-specific target 24-hour area under the curve to minimum inhibitory concentration ratios in the vitreous humor of the eye against the 4 most common causative bacteria seen in PTBIE. Results: Moxifloxacin 400 mg po daily (M400) achieved the highest CFR (72%). Levofloxacin dosing options achieved CFRs between 54% and 63%. Ciprofloxacin dosing options achieved CFRs between 28% and 35%. Conclusion: M400 optimized the likelihood of prophylactic success in the prevention of PTBIE, and based on the study findings, M400 is predicted to optimize the probability of success compared with ciprofloxacin and levofloxacin dosing options currently endorsed by expert opinion.

The impact of vancomycin trough concentrations on outcomes in non-deep seated infections: a retrospective cohort study.

BACKGROUND: Guidelines recommending vancomycin trough concentrations > 10 mg/L in non-deep seated infections are based on expert opinion. The objective of this study was to evaluate patients with non-deep seated infections treated with short-course vancomycin to determine whether there were differences in outcomes with trough concentrations of ≤10 mg/L (low) versus > 10 mg/L (high). METHODS: A retrospective cohort study of patients hospitalized between March 10, 2010 and December 31, 2015 who received ≤14 days of vancomycin to treat a non-deep seated infection and had at least one steady state trough concentration was completed. Patient data for the low versus high trough cohorts were compared using appropriate statistical tests and binary logistic regression was used to identify factors associated with clinical outcome. RESULTS: Of 2098 patients screened, 103 (5%) met inclusion criteria. Baseline characteristics between cohorts were not different. Clinical cure was not different between the low (42/48 [88%]) and high trough (48/55 [87%]) cohorts (p > 0.99) and vancomycin trough concentration was not associated with clinical outcome (p = 0.973). More patients in the high trough group had dosing changes (7/48 [15%] vs. 22/55 [40%], p = 0.0046), with approximately three times more dose adjustments per patient (0.17 vs. 0.55, p = 0.0193). No signal for increased vancomycin resistance associated with vancomycin troughs was identified. CONCLUSIONS: No difference in clinical or microbiological outcomes based on vancomycin trough concentrations were observed in patients with non-deep seated infections treated with vancomycin for ≤14 days. Targeting higher vancomycin trough concentrations of > 10 mg/L may be associated with increased workload with no corresponding benefit in clinical or microbiological outcomes in these patients.

Steady-State Pharmacokinetics of Oral Ciprofloxacin in Continuous Cycling Peritoneal Dialysis Patients: Brief Report.

Steady-state pharmacokinetics of oral ciprofloxacin in 3 continuous cycling peritoneal dialysis (CCPD) outpatients given ciprofloxacin 750 mg b.i.d. for 5 doses was determined. Mean steady-state maximum serum concentration and half-life were 4.4 ± 1.5 mg/L and 10.3 ± 2.6 hours, respectively. Mean maximum dialysate concentration in the daytime long dwell and overnight continuous cycling dwell were 7.4 ± 1.2 mg/L and 3.3 ± 1.2 mg/L, respectively. Oral ciprofloxacin 750 mg b.i.d. may be reasonable for bloodstream and peritoneal infections caused by susceptible bacteria in CCPD patients.

Point-of-Care ß-Lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation.

Background: ß-lactam allergy skin testing (BLAST) is recommended by antimicrobial stewardship program (ASP) guidelines, yet few studies have systematically evaluated its impact when delivered at point of care. Methods: We conducted a pragmatic multicenter prospective evaluation of the use of point-of-care BLAST by ASPs. In staggered 3-month intervals, ASP teams at 3 hospitals received training by allergists to offer BLAST for eligible patients with infectious diseases receiving nonpreferred therapy due to severity of their reported allergy. The primary outcome was the proportion of patients receiving the preferred ß-lactam therapy. Results: Of 827 patients with reported ß-lactam allergy over 15 months, ß-lactam therapy was preferred among 632 (76%). During baseline periods, 50% (124/246) received preferred ß-lactam therapy based on history, compared with 60% (232/386) during the intervention periods (P = .02), which improved further to 81% (313/386) upon provision of BLAST (P < .001) without any increase in incidence of adverse drug reactions (4% vs 3%; P = .4). After adjusting for patient variables and the correlation between hospitals, the intervention period was associated with a 4.5-fold greater odds of receiving preferred ß-lactam therapy (95% confidence interval, 2.4-8.2; P < .0001). Conclusions: The use of BLAST at the point of care across 3 hospital ASPs resulted in greater use of preferred ß-lactam therapy without increasing the risk of adverse drug reactions. Longer-term studies are needed to better assess the safety and clinical impact of this ASP intervention.

Impact of hospital length of stay on the distribution of Gram negative bacteria and likelihood of isolating a resistant organism in a Canadian burn center.

RATIONALE: The impact of hospital length of stay (LOS) on the distribution and susceptibility of Gram negative bacteria (GNB) causing infection in burn patients remains unexplored. Knowledge of causative pathogens is important in guiding empiric antibiotic therapy. OBJECTIVES: To characterize the distribution of GNB causing infection and to identify changes in susceptibility with LOS in a tertiary care burn center. METHODS: A retrospective review of all admissions to the Ross Tilley Burn Centre at Sunnybrook Health Sciences Centre with clinical cultures yielding GNB (duplicates excluded) between March 12, 2010 to July 17, 2013 was completed. Positive cultures were categorized into 5 clinically relevant time periods (in days) based on specimen collection date relative to the patient's date of admission: 0-7, 7-14, 14-21, 21-28, >28. Chi-square for proportions was used to compare the time periods. RESULTS: The proportion of patients with clinical cultures for P. aeruginosa increased with hospital LOS (0-7 days: 8% vs. >28 days: 55%; p<0.05). Conversely, clinical cultures for H. influenzae occurred primarily within the first 7 days of hospitalization (0-7 days: 36% vs. >28 days: 0.7%; p<0.05). Enterobacteriaceae isolation was highest between 7 and 14 days of hospitalization (7-14 days: 62% vs. >28 days: 38%; p<0.05). Antibiotic resistance was directly proportional to hospital LOS (% patients with multidrug resistant GNB increased from 6% [LOS 0-7 days] to 44% [LOS>28 days]; p<0.05). CONCLUSIONS: This study provides objective data documenting changes in species and resistance patterns of GNB causing infection in patients admitted to a burn center as a function of hospital LOS; which may support delaying the use of broad spectrum antibiotics (e.g. carbapenems and beta-lactam/beta-lactamase inhibitors) in clinically stable patients.

Antibiotic Use and Need for Antimicrobial Stewardship in Long-Term Care.

BACKGROUND: Antimicrobial stewardship may be important in long-term care facilities because of unnecessary or inappropriate antibiotic use observed in these residents, coupled with their increased vulnerability to health care-associated infections. OBJECTIVES: To assess antibiotic use in a long-term care facility in order to identify potential antimicrobial stewardship needs. METHODS: A retrospective descriptive study was conducted at the Veterans Centre, a long-term care facility at Sunnybrook Health Sciences Centre, Toronto, Ontario. All residents taking one or more antibiotics (n = 326) were included as participants. Antibiotic-use data for patients residing in the facility between April 1, 2011, and March 31, 2012, were collected and analyzed. RESULTS: Totals of 358 patient encounters, 835 antibiotic prescriptions, and 193 positive culture results were documented during the study period. For 36% (302/835) of antibiotic prescriptions, the duration was more than 7 days. Cephalosporins (30%; 251/835) and fluoroquinolones (28%; 235/835) were the most frequently prescribed antibiotic classes. Urine was the most common source of samples for culture (60%; 116/193). CONCLUSIONS: Characteristics of antimicrobial use at this long-term care facility that might benefit from further evaluation included potentially excessive use of fluoroquinolones and cephalosporins and potentially excessive duration of antibiotic use for individual patients.

CONTEXTE: La gérance des antibiotiques peut s'avérer importante au sein des établissements de soins de longue durée à cause d'une utilisation inutile ou inappropriée des antibiotiques chez les résidents de ces établissements et de leur vulnérabilité aux infections nosocomiales. OBJECTIFS: Évaluer l'utilisation des antibiotiques dans un établissement de soins de longue durée afin de déterminer si une gérance des antimicrobiens peut être nécessaire. MÉTHODES: Une étude descriptive rétrospective a été réalisée au Veterans Centre, un établissement de soins de longue durée au sein du Sunnybrook Health Sciences Centre, à Toronto en Ontario. Tous les résidents prenant au moins un antibiotique (n = 326) ont été admis à l'étude. Des données sur les antibiothérapies pour des patients résidant dans l'établissement entre le 1er avril 2011 et le 31 mars 2012 ont été recueillies et analysées. RÉSULTATS: Pendant l'étude, on a consigné en tout 358 séjours de patients, 835 prescriptions d'antibiotiques et 193 résultats positifs de culture. Pour 36 % (302/835) des prescriptions d'antibiotiques, le traitement était de plus de 7 jours. Les céphalosporines (30 % [251/835]) et les fluoroquinolones (28 % [235/835]) étaient les antibiotiques les plus souvent prescrits. Les cultures étaient le plus souvent obtenues à partir d'urines (60 % [116/193]). CONCLUSIONS: L'utilisation possiblement excessive de fluoroquinolones et de céphalosporines ainsi que la durée potentiellement exagérée des antibiothérapies font partie des caractéristiques de l'emploi des antimicrobiens dans cet établissement de soins de longue durée qui pourraient mériter de plus amples évaluations.

Outcomes in Documented Pseudomonas aeruginosa Bacteremia Treated with Intermittent IV Infusion of Ceftazidime, Meropenem, or Piperacillin-Tazobactam: A Retrospective Study.

BACKGROUND: Pseudomonas aeruginosa, one of the leading causes of nosocomial gram-negative bloodstream infections, is particularly difficult to treat because of its multiple resistance mechanisms combined with a lack of novel antipseudomonal antibiotics. Despite knowledge of time-dependent killing with ß-lactam antibiotics, most hospitals in Canada currently administer ß-lactam antibiotics by intermittent rather than extended infusions. OBJECTIVES: To determine clinical outcomes, microbiological outcomes, total hospital costs, and infection-related costs for patients with P. aeruginosa bacteremia who received intermittent IV administration of antipseudomonal ß-lactam antibiotics in a tertiary care institution. METHODS: For this retrospective descriptive study, data were collected for patients who were admitted between March 1, 2005, and March 31, 2013, who had P. aeruginosa bacteremia during their admission, and who received at least 72 h of treatment with ceftazidime, meropenem, or piperacillin-tazobactam. Clinical and microbiological outcomes were determined, and total and infection-related hospital costs were calculated. RESULTS: A total of 103 patients were included in the analysis, of whom 79 (77%) experienced clinical cure. In addition, bacterial eradication was achieved in 41 (87%) of the 47 patients with evaluable data for this outcome. Twenty-eight (27%) of the 103 patients died within 30 days of discontinuation of antipseudomonal ß-lactam antibiotic therapy. The median total cost of the hospital stay was $121 718, and the median infection-related cost was $29 697. CONCLUSIONS: P. aeruginosa bacteremia is a clinically significant nosocomial infection that continues to cause considerable mortality and health care costs. To the authors' knowledge, no previous studies have calculated total and infection-related hospital costs for treatment of P. aeruginosa bacteremia with intermittent infusion of antipseudomonal ß-lactam antibiotics, with characterization of cost according to site of acquisition of the infection. This study may provide important baseline data for assessing the impact of implementing extended-infusion ß-lactam therapy, antimicrobial stewardship, and infection control strategies targeting P. aeruginosa infection in hospitalized patients.

CONTEXTE: La bactérie Pseudomonas aeruginosa, l'une des principales causes des bactériémies nosocomiales à Gram négatif, est particulièrement difficile à traiter, parce qu'elle possède de nombreux mécanismes de résistance et qu'il n'y a pas de nouveaux antibiotiques anti-Pseudomonas. Bien que l'on sache que l'effet bactéricide des ß-lactamines est fonction du temps, la plupart des hôpitaux au Canada administrent actuellement ces antibiotiques par perfusions intermittentes plutôt que prolongées. OBJECTIFS: Déterminer quels sont les résultats cliniques, les résultats microbiologiques, les coûts totaux d'hospitalisation et ceux liés à l'infection seule pour les patients atteints d'une bactériémie à P. aeruginosa ayant reçu des ß-lactamines anti-Pseudomonas par perfusion intermittente dans un établissement de soins tertiaires. MÉTHODES: Pour la présente étude rétrospective descriptive, on a recueilli des données sur des patients hospitalisés entre le 1er mars 2005 et le 31 mars 2013, qui étaient atteints d'une bactériémie à Pseudomonas aeruginosa, et qui ont reçu au moins 72 heures de traitements par ceftazidime, méropenem ou pipéracilline-tazobactam. Les résultats cliniques et microbiologiques ont été déterminés, et les coûts totaux d'hospitalisation et ceux liés à l'infection ont été calculés. RÉSULTATS: En tout, 103 patients ont été retenus pour l'analyse. Parmi eux, 79 (77 %) ont joui d'une guérison clinique. De plus, une éradication bactérienne a été obtenue chez 41 (87 %) des 47 patients ayant des données évaluables pour ce résultat. Vingt-huit (27 %) des 103 patients sont décédés dans les trente jours suivant la fin de l'antibiothérapie par ß-lactamines anti-Pseudomonas. Le coût total médian du séjour à l'hôpital était de 121 718 $ et le coût médian lié à l'infection était de 29 697 $. CONCLUSIONS: La bactériémie à Pseudomonas aeruginosa est une infection nosocomiale cliniquement significative. Elle demeure à ce jour une cause importante de mortalité et une source considérable de coûts de soins de santé. À la connaissance des auteurs, aucune étude antérieure n'a calculé les coûts totaux d'hospitalisation et ceux liés à l'infection pour le traitement de la bactériémie à Pseudomonas aeruginosa par perfusion intermittente de ß-lactamines anti-Pseudomonas, en caractérisant ces coûts selon le site de transmission de l'infection. Cette étude pourrait fournir d'importantes données de référence pour évaluer l'effet de la mise en place du traitement par perfusion prolongée de ß-lactamines, d'une gestion responsable des antimicrobiens et de stratégies de prévention des infections qui visent l'infection à P. aeruginosa chez les patients hospitalisés.

Point prevalence survey of antimicrobial utilization in a Canadian tertiary-care teaching hospital.

OBJECTIVES: Inappropriate antimicrobial use can promote antimicrobial resistance, which is associated with increased patient morbidity and mortality. Identifying the pattern of antimicrobial use can provide data from which targeted antimicrobial stewardship interventions can be made. The primary objective was to identify the prevalence of antimicrobial use at a tertiary care teaching hospital with both acute and long-term care patients. METHODS: A point prevalence study was conducted on July 19th, 2012. Data on antimicrobial utilization, indication for prescribing, duration of therapy, and frequency of infectious disease or antimicrobial stewardship consultations were collected using a customized integrated stewardship database (SPIRIT) and prospective chart review. RESULTS: One or more antimicrobial agents were ordered in 31% and 4% of acute care and long-term care patients, respectively. Respiratory and urinary tract infections were the most common indication for antimicrobial therapy in both acute and long-term care. About 25% of surgical prophylaxis orders were prescribed for greater than 24h. CONCLUSION: This prospective point prevalence survey provided important baseline information on antimicrobial use within a large tertiary care teaching hospital and identified potential targets for future antimicrobial stewardship initiatives. A multi-center point prevalence survey should be considered to identify patterns of antimicrobial use in Canada and to establish the first steps toward international antimicrobial surveillance.

Lessons from audit and feedback of hospitalized patients with bacteriuria.

We sought to prevent the initiation of antimicrobial therapy for asymptomatic bacteriuria (ASB) by providing audit and feedback of newly reported positive urine cultures to test whether this could empower providers to leave ASB untreated. Despite success in providing feedback before antibiotics could be initiated in most cases, these recommendations only reduced treatment duration, without affecting antibiotic initiation. This study highlights the limitations of educational initiatives in overcoming engrained beliefs about bacteriuria even when advice is provided in real time.

Weighted-incidence syndromic combination antibiograms to guide empiric treatment of critical care infections: a retrospective cohort study.

INTRODUCTION: Empiric antimicrobial selection for critical care infections must balance the need for timely adequate coverage with the resistance pressure exerted by broadspectrum agents. We estimated the potential of weighted incidence syndromic combination antibiograms (WISCAs) to improve time to adequate coverage for critical care infections. In contrast to traditional antibiograms, WISCAs display the likelihood of coverage for a specific infectious syndrome (rather than individual pathogens), and also take into account the potential for poly-microbial infections and the use of multi-drug regimens. METHODS: Cases of ventilator-associated pneumonia (VAP) and catheter-related bloodstream infection (CRBSI) were identified over three years using stringent surveillance criteria. Based on the susceptibility profile of the culprit pathogens, we calculated the WISCA percentages of infections that would have been adequately covered by common antimicrobial(s). We then computed the excess percentage coverage offered by WISCA regimens compared to the actual antimicrobials administered to patients by 12 h, 24 h, and 48 h from culture collection. RESULTS: Among 163 patients with critical care infection, standard practice only resulted in adequate coverage of 35% of patients by 12 h, 52% by 24 h, and 75% by 48 h. No WISCA mono-therapy regimen offered greater than 85% adequate overall coverage for VAP and CRBSI. A wide range of dual therapy regimens would have conferred greater than 90% adequate coverage, with excess coverage estimated to be as high as +56%, +42% and +18% at 12 h, 24 h and 48 h, respectively. We did not detect a decrease in mortality associated with early adequate treatment, and so could not estimate potential downstream benefits. CONCLUSIONS: WISCA-derived empiric antimicrobial regimens can be calculated for patients with intensive care unit (ICU)-acquired infections, and have the potential to reduce time to adequate treatment. Prospective research must confirm whether implementation of WISCA prescribing aids facilitate timely adequate treatment and improved ICU outcomes.

Hospital-wide rollout of antimicrobial stewardship: a stepped-wedge randomized trial.

Our objective was to rigorously evaluate the impact of an antimicrobial stewardship audit-and-feedback intervention, via a stepped-wedge randomized trial. An effective intensive care unit (ICU) audit-and-feedback program was rolled out to 6 non-ICU services in a randomized sequence. The primary outcome was targeted antimicrobial utilization, using a negative binomial regression model to assess the impact of the intervention while accounting for secular and seasonal trends. The intervention was successfully transitioned, with high volumes of orders reviewed, suggestions made, and recommendations accepted. Among patients meeting stewardship review criteria, the intervention was associated with a large reduction in targeted antimicrobial utilization (-21%, P = .004); however, there was no significant change in targeted antibiotic use among all admitted patients (-1.2%, P = .9), and no reductions in overall costs and microbiologic outcomes. An ICU day 3 audit-and-feedback program can be successfully expanded hospital-wide, but broader benefits on non-ICU wards may require interventions earlier in the course of treatment.

Symptom reporting compared with audiometry for the detection of cochleotoxicity in patients on long-term aminoglycoside therapy.

BACKGROUND: Aminoglycoside-associated auditory toxicity (cochleotoxicity) is a major concern in patients receiving prolonged aminoglycoside therapy. There are no published data comparing symptom monitoring to audiometry testing for the detection of aminoglycoside-induced cochleotoxicity; thus, agreement regarding the optimal monitoring of these patients for early detection of this effect is lacking. OBJECTIVE: To compare the sensitivity of symptom monitoring to that of audiometry in identifying cochleotoxicity in patients on prolonged aminoglycoside therapy. METHODS: A retrospective chart review of adult inpatients at Sunnybrook Health Sciences Centre prescribed prolonged aminoglycoside therapy (≥21 days) who completed at least 1 audiometry test between January 1, 1999, and December 31, 2009, was conducted. Data pertaining to results of audiometry testing and development of symptoms of auditory toxicity were collected. Symptom monitoring was compared with audiology testing for the detection of cochleotoxicity. RESULTS: Forty eligible patients were included for analysis. Audiometry was significantly better than symptom monitoring to identify early cochleotoxicity (absolute risk reduction = 17.5% and number needed to treat = 6; p = 0.023). Compared to audiometry, symptom monitoring has a sensitivity, negative predictive value, and accuracy for the detection of early cochleotoxicity of 61%, 75%, and 82%, respectively. CONCLUSIONS: Audiometry testing is significantly better than monitoring symptoms to identify early aminoglycoside-induced auditory toxicity in patients prescribed prolonged aminoglycoside therapy (≥21 days). Subclinical cochleotoxicity identified with audiometry may allow early termination of aminoglycoside therapy to prevent progression of cochlear damage to the audible frequency range.

Impact of antimicrobial stewardship in critical care: a systematic review.

OBJECTIVES: To evaluate the current state of evidence for antimicrobial stewardship interventions in the critical care unit. METHODS: We performed a systematic search of OVID MEDLINE, Embase and Cochrane electronic databases from 1996-2010. Studies were included if they involved any experimental intervention to improve antimicrobial utilization in the critical care setting. RESULTS: Thirty-eight studies met the inclusion criteria, of which 24 met our quality inclusion criteria. The quality of research was poor, with only 3 randomized controlled trials, 3 interrupted time series and 18 (75%) uncontrolled before-and-after studies. We identified six intervention types: studies of antibiotic restriction or pre-approval (six studies); formal infectious diseases physician consultation (five); implementation of guidelines or protocols for de-escalation (two); guidelines for antibiotic prophylaxis or treatment in intensive care (two); formal reassessment of antibiotics on a pre-specified day of therapy (three); and implementation of computer-assisted decision support (six). Stewardship interventions were associated with reductions in antimicrobial utilization (11%-38% defined daily doses/1000 patient-days), lower total antimicrobial costs (US$ 5-10/patient-day), shorter average duration of antibiotic therapy, less inappropriate use and fewer antibiotic adverse events. Stewardship interventions beyond 6 months were associated with reductions in antimicrobial resistance rates, although this differed by drug-pathogen combination. Antibiotic stewardship was not associated with increases in nosocomial infection rates, length of stay or mortality. CONCLUSIONS: More rigorous research is needed, but available evidence suggests that antimicrobial stewardship is associated with improved antimicrobial utilization in the intensive care unit, with corresponding improvements in antimicrobial resistance and adverse events, and without compromise of short-term clinical outcomes.