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 ∼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 120% 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.
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BFBNIB, NUK, PNG, UL, UM, UPUK
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background. Colistin, originally abandoned due to high rates of nephrotoxicity, has been recently reintroduced due to activity against carbapenem-resistant Gram-negative organisms. Recent literature, ...largely obtained from outside the United States, suggests a lower rate of nephrotoxicity than historically reported. Methods. A retrospective cohort of all patients who received colistin for ≥48 hours at the Detroit Medical Center over a 5-year period was performed to determine the rate of colistin-associated nephrotoxicity as defined by the RIFLE criteria. Results. Fifty-four (43%) patients in the cohort developed nephrotoxicity. Patients who experienced nephrotoxicity after colistin administration were in the Risk (13%), Injury (17%), or Failure (13%) categories per RIFLE criteria. Patients who developed nephrotoxicity received significantly higher mean doses than those who did not (5.48 mg/kg per day vs 3.95 mg/kg per day; P <.001), and the toxicity occurred in a dose-dependent fashion. Independent predictors for nephrotoxicity were a colistin dose of ≥5.0 mg/kg per day of ideal body weight (odds ratio OR, 23.41; 95% confidence interval CI, 5.3—103.55), receipt of concomitant rifampin (OR, 3.81; 95% CI, 1.42—10.2), and coadministration of ≥3 concomitant nephrotoxins (OR, 6.80; 95% CI, 1.42—32.49). Conclusions. In this retrospective cohort, nephrotoxicity (as defined by RIFLE criteria) occurred among 43% of treated patients in a dose-dependent manner. Higher colistin doses, similar to those commonly used in the United States, led to a relatively high rate of nephrotoxicity. These data raise important questions regarding the safe use of colistin in the treatment of multidrug-resistant pathogens.
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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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
For many species, a well documented response to anthropogenic climate change is a shift in various aspects of its life history, including its timing or phenology. Often, these phenological ...shifts are associated with changes in abiotic factors used as proxies for resource availability or other suitable conditions. Resource availability, however, can also be impacted by competition, but the impact of competition on phenology is less studied than abiotic drivers. We fit generalized additive models (GAMs) to a long‐term experimental dataset on small mammals monitored in the southwestern United States and show that altered competitive landscapes can drive shifts in breeding timing and prevalence, and that, relative to a dominant competitor, other species exhibit less specific responses to environmental factors. These results suggest that plasticity of phenological responses, which is often described in the context of annual variation in abiotic factors, can occur in response to biotic context as well. Variation in phenological responses under different biotic conditions shown here further demonstrates that a more nuanced understanding of shifting biotic interactions is useful to better understand and predict biodiversity patterns in a changing world.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To evaluate the impact of methicillin resistance in Staphylococcus aureus on mortality, length of hospitalization, and hospital charges.
A cohort study of patients admitted to the hospital between ...July 1, 1997, and June 1, 2000, who had clinically significant S. aureus bloodstream infections.
A 630-bed, urban, tertiary-care teaching hospital in Boston, Massachusetts.
Three hundred forty-eight patients with S. aureus bacteremia were studied; 96 patients had methicillin-resistant S. aureus (MRSA). Patients with methicillin-susceptible S. aureus (MSSA) and MRSA were similar regarding gender, percentage of nosocomial acquisition, length of hospitalization, ICU admission, and surgery before S. aureus bacteremia. They differed regarding age, comorbidities, and illness severity score.
Similar numbers of MRSA and MSSA patients died (22.9% vs 19.8%; P = .53). Both the median length of hospitalization after S. aureus bacteremia for patients who survived and the median hospital charges after S. aureus bacteremia were significantly increased in MRSA patients (7 vs 9 days, P = .045; 19,212 dollars vs 26,424 dollars, P = .008). After multivariable analysis, compared with MSSA bacteremia, MRSA bacteremia remained associated with increased length of hospitalization (1.29 fold; P = .016) and hospital charges (1.36 fold; P = .017). MRSA bacteremia had a median attributable length of stay of 2 days and a median attributable hospital charge of 6916 dollars.
Methicillin resistance in S. aureus bacteremia is associated with significant increases in length of hospitalization and hospital charges.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Multidrug-resistant organisms (MDROs) are prevalent on high-touch surfaces in multi-patient rooms.
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.
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.
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).
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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 (LOS
) 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 LOS
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 LOS
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 LOS
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, LOS
values were similar between treatment groups. Clinical and nonclinical factors were associated with LOS
.
To explore contemporary antibiotic management of infections caused by carbapenem-resistant Gram-negative bacteria in hospitals.
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.
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.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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