The impact of bedside wipes in multi-patient rooms: a prospective, crossover trial evaluating infections and survival.

BACKGROUND: Multidrug-resistant organisms (MDROs) are prevalent on high-touch surfaces in multi-patient rooms. AIM: To quantify the impact of hanging single-use cleaning/disinfecting wipes next to each bed. Pre-specified outcomes were: (1) hospital-acquired infections (HAIs), (2) cleaning frequency, (3) MDRO room contamination, (4) new MDRO acquisitions, and (5) mortality. METHODS: Clustered randomized crossover trial at Shamir Medical Center, Israel (October 2016 to January 2018). Clusters were randomly assigned to use for cleaning either single-use quaternary ammonium wipes (Clinell) or standard practices (reusable cloths and buckets with bleach). Six-month intervention periods were implemented in alternating sequence, separated by a washout period. Five high-touch surfaces were monitored by fluorescent markers. Study outcomes were compared between periods using generalized estimating equations, Poisson regression, and Cox proportional hazards models. FINDINGS: Overall, 7725 patients were included (47,670 person-days), 3793 patients in rooms with intervention cleaning and 3932 patients in rooms with standard practices. During the intervention, there was no significant difference in HAI rates (incidence rate ratio: 1.6; 95% confidence interval (CI): 0.7-3.5; P = 0.3). However, in intervention rooms, the frequency of environmental cleaning was higher (odds ratio: 3.73; 95% CI: 2.0-7.1; P < 0.0001), MDRO environmental contamination rate was insignificantly lower (odds ratio: 0.7; 95% CI: 0.5-1.0; P = 0.06), new MDRO acquisition rate was lower (hazard ratio: 0.4; 95% CI: 0.2-1.0; P = 0.04), and in-hospital mortality rate was lower (incidence rate ratio: 0.8; 95% CI: 0.7-1.0; P = 0.03). CONCLUSION: Hanging single-use cleaning/disinfecting wipes next to each bed did not affect the HAI rates but did improve the frequency of cleaning, reduce MDRO environmental contamination, and was associated with reduced incidence of new MDRO acquisitions and reduced mortality. This is a feasible, recommended practice to improve patient outcomes in multi-patient rooms.

Multicenter Study of the Real-World Use of Ceftaroline versus Vancomycin for Acute Bacterial Skin and Skin Structure Infections.

The objective of this study was to determine if real-world ceftaroline treatment in adults hospitalized for acute bacterial skin and skin structure infections (ABSSSI) is associated with decreased infection-related length of stay (LOSinf) compared to that with vancomycin. This was a retrospective, multicenter, cohort study from 2012 to 2017. Cox proportional hazard regression, propensity score matching, and inverse probability of treatment weighting (IPTW) were used to determine the independent effect of treatment group on LOSinf The patients were adults hospitalized with ABSSSI and treated with ceftaroline or vancomycin for ≥72 h within 120 h of diagnosis at four academic medical centers and two community hospitals in Arizona, Florida, Michigan, and West Virginia. A total of 724 patients were included (325 ceftaroline treated and 399 vancomycin treated). In general, ceftaroline-treated patients had characteristics consistent with a higher risk of poor outcomes. The unadjusted median LOSinf values were 5 (interquartile range [IQR], 3 to 7) days and 6 (IQR, 4 to 8) days in the vancomycin and ceftaroline groups, respectively (hazard ratio [HR], 0.866; 95% confidence interval [CI], 0.747 to 1.002). The Cox proportional hazard model (adjusted HR [aHR], 0.891; 95% CI, 0.748 to 1.060), propensity score-matched (aHR, 0.955; 95% CI, 0.786 to 1.159), and IPTW (aHR, 0.918; 95% CI, 0.793 to 1.063) analyses demonstrated no significant difference in LOSinf between groups. Patients treated with ceftaroline were significantly more likely to meet criteria for discharge readiness at day 3 in unadjusted and adjusted analyses. Although discharge readiness at day 3 was higher in ceftaroline-treated patients, LOSinf values were similar between treatment groups. Clinical and nonclinical factors were associated with LOSinf.

Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infectious diseases specialists practicing in large hospitals.

OBJECTIVES: To explore contemporary antibiotic management of infections caused by carbapenem-resistant Gram-negative bacteria in hospitals. METHODS: Cross-sectional, internet-based questionnaire survey. We contacted representatives of all hospitals with more than 800 acute-care hospital beds in France, Greece, Israel, Italy, Kosovo, Slovenia, Spain and selected hospitals in the USA. We asked respondents to describe the most common actual practice at their hospital regarding management of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa through close-ended questions. RESULTS: Between January and June 2017, 115 of 141 eligible hospitals participated (overall response rate 81.6%, country-specific rates 66.7%-100%). Most were tertiary-care (99/114, 86.8%), university-affiliated (110/115, 89.1%) hospitals and most representatives were infectious disease specialists (99/115, 86.1%). Combination therapy was prescribed in 114/115 (99.1%) hospitals at least occasionally. Respondents were more likely to consider combination therapy when treating bacteraemia, pneumonia and central nervous system infections and for Enterobacteriaceae, P. aeruginosa and A. baumannii similarly. Combination of a polymyxin with a carbapenem was used in most cases, whereas combinations of a polymyxin with tigecycline, an aminoglycoside, fosfomycin or rifampicin were also common. Monotherapy was used for treatment of complicated urinary tract infections, usually with an aminoglycoside or a polymyxin. The intended goal of combination therapy was to improve the effectiveness of the treatment and to prevent development of resistance. In general, respondents shared the misconception that combination therapy is supported by strong scientific evidence. CONCLUSIONS: Combination therapy was the preferred treatment strategy for infections caused by carbapenem-resistant Gram-negative bacteria among hospital representatives, even though high-quality evidence for carbapenem-based combination therapy is lacking.

Clinical considerations for optimal use of the polymyxins: A focus on agent selection and dosing.

Polymyxins have remained the drug of choice for treatment due to carbapenem-resistant Gram-negative bacilli. Unfortunately, the utility of these agents has been limited by a lack of pharmacokinetic understanding, a high toxicity rate, and an extremely narrow therapeutic index. Significant advancements have been achieved in the understanding of the polymyxins over the past decade, and have led to the recognition of several differences between available intravenous formulations. The purpose of this review is to discuss the implications of these differences, assess comparative efficacy and safety of the polymyxins, and provide recommendations for polymyxin dosing and selection.

Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition.

OBJECTIVES: To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). METHODS: Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. RESULTS: Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. CONCLUSIONS: These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes.

Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections.

Patients infected or colonized with carbapenem-resistant Klebsiella pneumoniae (CRKp) are often chronically and acutely ill, which results in substantial mortality unrelated to infection. Therefore, estimating excess mortality due to CRKp infections is challenging. The Consortium on Resistance against Carbapenems in K. pneumoniae (CRACKLE) is a prospective multicenter study. Here, patients in CRACKLE were evaluated at the time of their first CRKp bloodstream infection (BSI), pneumonia or urinary tract infection (UTI). A control cohort of patients with CRKp urinary colonization without CRKp infection was constructed. Excess hospital mortality was defined as mortality in cases after subtracting mortality in controls. In addition, the adjusted hazard ratios (aHR) for time-to-hospital-mortality at 30 days associated with infection compared with colonization were calculated in Cox proportional hazard models. In the study period, 260 patients with CRKp infections were included in the BSI (90 patients), pneumonia (49 patients) and UTI (121 patients) groups, who were compared with 223 controls. All-cause hospital mortality in controls was 12%. Excess hospital mortality was 27% in both patients with BSI and those with pneumonia. Excess hospital mortality was not observed in patients with UTI. In multivariable analyses, BSI and pneumonia compared with controls were associated with aHR of 2.59 (95% CI 1.52-4.50, p <0.001) and 3.44 (95% CI 1.80-6.48, p <0.001), respectively. In conclusion, in patients with CRKp infection, pneumonia is associated with the highest excess hospital mortality. Patients with BSI have slightly lower excess hospital mortality rates, whereas excess hospital mortality was not observed in hospitalized patients with UTI.

Appropriate antimicrobial therapy in the era of multidrug-resistant human pathogens.

The past decade has brought a significant rise in antimicrobial resistance, and the ESKAPE pathogens have become a significant threat to public health. Three epidemiological features that negatively impact patients, which are consistently seen with the ESKAPE pathogens, are the following: 1) there has been a rise in incidence of these organisms as causative human pathogens, 2) there has been a significant increase in antimicrobial resistance in these bacterial species, and 3) the infections caused by these resistant strains are associated with worse outcomes when compared with infections caused by their susceptible counterparts. Significant delays in time to appropriate antimicrobial therapy of up to 5 days have been reported in infections due to these organisms and this is the strongest predictor of mortality with ESKAPE pathogens, particular in critically ill patients, where every hour delay has an incremental survival disadvantage for patients. Strategies to decrease these delays are urgently needed. Although routine broad-spectrum empiric coverage for these organisms would ideally limit this delay, agents with activity against these organisms are sometimes less effective, have significant toxicity risk, and their use can result in the development of resistance. Therefore, strategies to optimize therapy, although limiting unnecessary use of broad-spectrum antimicrobials, are urgently needed. This review will discuss potential strategies to optimize empiric therapy in the age of multi-drug resistance, the limitations of these strategies, and will discuss future directions and opportunities.

Tigecycline therapy for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria leads to tigecycline resistance.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasing global threat. Here, we describe the prevalence and impact of tigecycline use in a cohort of patients with CRKP bacteriuria nested within a multicentre, prospective study. In the 21-month study period, 260 unique patients were included. Tigecycline was given to 80 (31%) patients. The use of tigecycline during the index hospitalization was significantly associated with the subsequent development of tigecycline resistance in the same patient (OR, 6.13; 95% CI, 1.15-48.65; p 0.03). In conclusion, the use of tigecycline with CRKP bacteriuria is common, and is associated with the subsequent development of tigecycline resistance.

Independent risk factors for the co-colonization of vancomycin-resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus in the region most endemic for vancomycin-resistant Staphylococcus aureus isolation.

In the majority of cases of vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant Enterococcus faecalis (VR E. faecalis) served as the vanA donor to S. aureus. Previous studies that evaluated the risk factors for co-colonization with VRE and MRSA did not differentiate between VR E. faecalis and VR E. faecium. This study aimed to identify variables associated with VR E. faecalis and MRSA co-colonization. A retrospective case-control study from January 2008 to December 2009 was conducted at the Detroit Medical Center. Data were extracted from charts and pharmacy records. Unique patients co-colonized with VR E. faecalis and MRSA (defined as isolation of MRSA within 7 days of VR E. faecalis isolation) were compared with patients with VR E. faecalis who were not co-colonized with MRSA. A total of 546 patients with VR E. faecalis isolation were identified. 85 (15.6 %) VR E. faecalis patients were co-colonized with MRSA and 461 (84.4 %) VR E. faecalis patients were not co-colonized with MRSA. The mean age of the study cohort was 65.9 ± 16.4 years, 424 (77.7 %) were African-American, and 270 (49.5 %) were residing in long-term care institutions. Independent predictors of co-colonization of VR E. faecalis and MRSA were male gender, impaired consciousness, ICU stay prior to VR E. faecalis isolation, indwelling devices, and isolation of VR E. faecalis from wounds. MRSA was frequently isolated from the same culture specimen as VR E. faecalis (n = 39, 45.9 %), most commonly from wounds. This large study of patients with VR E. faecalis identified the severity of illness, indwelling devices, and chronic wounds as independent predictors of co-colonization with VR E. faecalis and MRSA.

The relationship between the new taxonomy of Streptococcus bovis and its clonality to colon cancer, endocarditis, and biliary disease.

BACKGROUND: The nomenclature of Streptococcus bovis has changed. The study aims were to examine and compare the clinical characteristics and outcomes of infections based on the new taxonomy and the genetic relatedness of strains. METHODS: Bacteremic cases from 2004 to 2010 at Assaf Harofeh Medical Center were reviewed. VITEK 2 later confirmed with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for subspecies identification. VITEK 2 later confirmed with Etests was used for minimal inhibitory concentration (MIC) testing. Repetitive extragenic palindromic polymerase chain reaction (rep-PCR) was used to determine the genetic relatedness of strains. RESULTS: Twenty-four bacteremia cases were included. The median age of patients was 81 years (range 1 day to 91 years), two were neonates, three were pregnant, and 18 were elderly (≥ 65 years of age). The Charlson's combined conditional age-related score was 8.2 ± 2.9, and 11 (58 %) patients were immunosuppressed. There were 13 patients who had S. gallolyticus subsp. pasteurianus, six had S. gallolyticus subsp. gallolyticus, four had S. infantarius subsp. coli, and one had S. infantarius subsp. infantarius. Ten of 19 non-pregnant adult patients had colon adenoma or carcinoma, three had acute biliary disease, and five had endocarditis. Two patients died in the hospital. rep-PCR revealed polyclonality. There were no significant associations between subspecies or genotypes and the various clinical characteristics or outcomes. CONCLUSION: S. bovis bacteremia is a serious disease that affects elderly immunosuppressed individuals. Infection is strongly associated with colon pathology and endocarditis, regardless of the new taxonomy or clone complex. The identification of S. bovis is of paramount importance, and microbiology laboratories should differentiate its processing from that of other S. viridans.

Multidrug-resistant Acinetobacter baumannii: an emerging pathogen among older adults in community hospitals and nursing homes.

BACKGROUND: Drug-resistant Acinetobacter species are problematic in tertiary-care hospitals. We describe the epidemiology, resistance patterns, and outcomes of older adults with Acinetobacter infection in community hospitals. METHODS: We queried the microbiology databases of the Oakwood Healthcare System (4 hospitals with 632, 259, 199, and 168 beds) for clinical Acinetobacter cultures obtained in 2003-2008. Patients aged 60 years who were admitted from home or nursing homes were included. We recorded the initial Acinetobacter isolate and susceptibility to 8 antibiotics. Cultures obtained 48 h after hospitalization were categorized as "nosocomial." Administrative databases provided patients' origins (home or nursing home) and discharge destinations (home, nursing home, long-term acute-care facility, another hospital, or hospice care or death). RESULTS: During the 6-year period, 560 community-dwelling (mean age +/- standard deviation, 74 +/- 8.6 years) and 280 nursing home-dwelling (78 +/- 9.1 years) patients had Acinetobacter isolated. During this period, Acinetobacter prevalence increased 25% (P<.001, by trend test). In comparison of 2003 with 2008, Acinetobacter resistance to imipenem and ampicillin/sulbactam increased (from 1.8% to 33.1%; P<.001), as did "panresistance" (ie, resistance to all 8 antibiotics; increase from 0.0% to 13.6%; P<.001). Although resistance was stable in community-acquired isolates (resistance to approximately 4.2 antibiotics), resistance increased among nursing home-acquired and nosocomial-acquired isolates (from 4.5 to 5.7 and from 5.0 to 6.0 antibiotics, respectively; P<.01). At discharge, only 25% of community-dwelling and 50% of nursing home-dwelling patients returned to their place of origin; the remainder required higher levels of care or died. After adjustment for age, length of stay, and origin, resistance to each additional antibiotic predicted a >20% increased risk for discharge to higher levels of care or death (odds ratio, 1.23; 95% confidence interval, 1.11-1.36). CONCLUSIONS: The prevalence and resistance of Acinetobacter species are increasing in the community. Patients with resistant isolates are selectively discharged to nursing homes and long-term acute-care facilities, introducing resistance to new facilities.

Case-control study to identify factors associated with mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with increased mortality. Delay in appropriate antimicrobial therapy (DAAT) is an important risk factor for death, although confounding between carriage of MRSA and DAAT has not been resolved. We studied the association of risk factors with mortality and searched for specific populations vulnerable to DAAT. We conducted a case-control study comparing patients with MRSA bacteraemia who died during hospitalization (cases) with patients with MRSA bacteraemia who survived (controls) in three medical centres in two states. Patients were identified using computerized hospital databases for the years 2001-2005. Medical records were retrieved and various epidemiological data extracted. Bivariate and multivariate logistic regression analyses were performed. Overall, 388 patients with MRSA bacteraemia were included, 164 cases and 224 controls. According to bivariate analyses, cases were significantly more likely than controls to (i) be older (>65 years), (ii) have transferred from an institution, (iii) have stayed in an ICU, (iv) have had more invasive devices, (v) have a poorer prognosis on admission, (vi) have higher disease severity at the time of bacteraemia, and (vii) have a DAAT of > or = 2 days. Upon multivariate analysis, among patients >65 years, DAAT was significantly associated with increased mortality (p 0.04). Furthermore, patients >65 years with severe sepsis were much more likely to experience DAAT (p 0.02). In elderly patients with MRSA bacteraemia, DAAT is associated with increased mortality. Moreover, advanced age is a predictor for DAAT. These significant epidemiological associations mandate early coverage of MRSA in septic elderly patients.

Alveolar adenoma of the lung: a clinicopathological description of a case of this very unusual tumour.

Alveolar adenomas are extremely rare, and are probably benign lung tumours of unknown histogenesis. This report describes a case of alveolar adenoma in a 43 year old white man, who presented with pleuritic chest pain. A chest x ray and computerised tomography scan demonstrated a solitary left lower lobe lung nodule. Although a positron emission tomography scan seemed to document the benign nature of the lesion, a thoracoscopic wedge resection was performed to alleviate the symptoms and verify the diagnosis. Histologically, the lesion was well demarcated, dominated by large and small cysts with no normal lung parenchyma. The interstitial cellular component consisted of both epithelioid and vaguely spindle shaped cells. The cystic cell linings were mostly indistinct, although areas of cuboidal epithelial cells were seen. Multiple histochemical and immunohistochemical tests were performed. There were no histological signs of malignancy and the patient is doing well one and a half years postoperatively.

Risk factors for postoperative mediastinitis due to methicillin-resistant Staphylococcus aureus.

Risk factors for developing postoperative mediastinitis (POM) due to methicillin-resistant Staphylococcus aureus (MRSA) were analyzed in a case-case control study of patients who underwent median sternotomy during the period from 1994 through 2000. Three patient groups were studied. The first consisted of 64 patients with POM due to MRSA; the second consisted of 79 patients with POM due to methicillin-susceptible S. aureus (MSSA); and the third consisted of 80 uninfected control patients. In multivariable analysis, patients who were diabetic (adjusted OR, 2.86; 95% CI, 1.22-6.70), female (OR, 2.70; 95% CI, 1.25-5.88), and >70 years old (OR, 3.43; 95% CI, 1.53-7.71) were more likely to develop POM due to MRSA. In contrast, the only independent risk factor associated with POM due to MSSA was obesity (OR, 2.49; 95% CI, 1.25-4.96). Antimicrobial prophylaxis consisted primarily of cephalosporin antibiotics (administered to 97% of the patients). Changes in perioperative antimicrobial prophylaxis, in addition to other interventions, should be considered for prevention of POM due to MRSA in targeted, high-risk populations.

Risk factors for emergence of resistance to broad-spectrum cephalosporins among Enterobacter spp.

Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistant Enterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of the patients receiving broad-spectrum cephalosporins, 19% developed resistance.

Preoperative drug dispensing as predictor of surgical site infection.

The system used by the National Nosocomial Infection Surveillance (NNIS) program to measure risk of surgical site infection uses a score of 3 on the American Society of Anesthesiologists (ASA)-physical status scale as a measure of underlying illness. The chronic disease score measures health status as a function of age, sex, and 29 chronic diseases, inferred from dispensing of prescription drugs. We studied the relationship between the chronic disease score and surgical site infection and whether the score can supplement the NNIS risk index. In a retrospective comparison of 191 patients with surgical site infection and 378 uninfected controls, the chronic disease score and ASA score were highly correlated. The chronic disease score improved prediction of infection by the NNIS risk index and augmented the ASA score for risk adjustment.

Pathogens resistant to antimicrobial agents. Epidemiology, molecular mechanisms, and clinical management.

The emergence of resistance to antimicrobial agents continues to be a major problem in the nosocomial setting and now in nursing homes and the community as well. Bacteria use a variety of strategies to avoid the inhibitory effects of antibiotic agents and have evolved highly efficient means for the dissemination of resistance traits. Control of antibiotic-resistant pathogens provides a major challenge for both the medical community and society in general. To control the emergence of resistant pathogens, CDC and infection control guidelines must be adhered to, and antibiotics must be used more judiciously.

Risk factors for recovery of ampicillin-sulbactam-resistant Escherichia coli in hospitalized patients.

Ampicillin-sulbactam resistance in Escherichia coli is an emerging problem. This study determined risk factors for the recovery of ampicillin-sulbactam-resistant E. coli in hospitalized patients. A case-control design was used to compare two groups of case patients with control patients. The first group of case patients consisted of patients from whom nosocomially acquired ampicillin-sulbactam-resistant E. coli strains were isolated, and the second group of case patients consisted of patients from whom ampicillin-sulbactam-susceptible E. coli strains were isolated. Control patients were a random selection among 5% of all patients admitted during the same time period. Risk factors analyzed included antimicrobial drug exposure, comorbid conditions, and demographics. Univariate and multivariate analyses were performed. Ampicillin-sulbactam-resistant E. coli strains were isolated from 175 patients, and ampicillin-sulbactam-susceptible E. coli strains were isolated from 577 patients. Nine hundred thirty-four control patients were selected. Exposure to penicillin antibiotics as a class and to ampicillin and ampicillin-sulbactam individually were the only significant, independent risk factors associated with the isolation of ampicillin-sulbactam-resistant E. coli (odds ratio [OR] = 2.32 [P < 0.001], OR = 3.04 [P = 0.02], and OR = 1.72 [P = 0.04], respectively), but they were not associated with the isolation of ampicillin-sulbactam-susceptible E. coli. Interestingly, exposure to piperacillin-tazobactam tended to protect against the isolation of E. coli strains resistant to ampicillin-sulbactam, but this did not reach statistical significance (OR = 0.13; P = 0.11).