Spontaneous bacterial peritonitis is a well-known complication of cirrhosis; however, spontaneous fungal peritonitis (SFP) is less well-recognised and described. Our objective was to determine the clinical characteristics, treatment outcomes and factors associated with death among patients with SFP. We performed a retrospective cohort study using the primary outcome of all-cause mortality at 28 days. Twenty-five patients were included; Candida species were the causative pathogen in all cases. At the onset of SFP, patients were critically ill, median APACHE II and MELD scores were 22 and 30.3, respectively. The 28-day mortality rate was 56%; six patients died prior to culture positivity. Among the remaining patients, there were no differences in rates of death by treatment regimen (P = 0.55). APACHE II score at the onset of SFP was an independent predictor of death (OR = 1.46, 95% CI = 1.02-2.08, P = 0.04). In conclusion, SFP develops among critically ill patients with cirrhosis and is associated with high rates of death. Directed antifungal therapy did not improve patient outcomes. Future studies assessing the benefit of early or pre-emptive antifungal therapy are warranted.

Limited data are available on ceftolozane/tazobactam dosing in patients receiving continuous renal replacement therapy (CRRT). Thus we performed a pharmacokinetic analysis of intravenous ceftolozane/tazobactam in a critically ill patient receiving CRRT at our medical center. A 47-year-old critically ill man with multidrug-resistant Pseudomonas aeruginosa pneumonia, bacteremia, and osteomyelitis was receiving ceftolozane/tazobactam 3 g (ceftolozane 2 g/tazobactam 1 g) every 8 hours while receiving continuous venovenous hemodiafiltration (CVVHDF). After the fifth dose of ceftolozane/tazobactam, plasma samples were obtained at 1-, 2-, 4-, 6-, and 8-hour time points. Two additional post-hemodialysis filter plasma samples were obtained to assess CVVHDF clearance. The maximum and minimum plasma concentrations for ceftolozane were 163.9 μg/ml and 79.4 μg/ml, respectively. The area under the plasma concentration-time curve from 0-8 hours (AUC ) was 689 μg hour/ml; the plasma half-life was 13.3 hours. The ceftolozane CVVHDF clearance and total clearance were 2.4 L/hour and 2.9 L/hour, respectively. Compared with a patient with normal renal function, this patient receiving CVVHDF had decreased ceftolozane clearance. A ceftolozane/tazobactam dosage of 1.5 g every 8 hours should adequately achieve a desired drug concentration above the minimum inhibitory concentration of 8 μg/ml for the treatment of pneumonia. Additional pharmacokinetic data are needed to confirm our results and for alternative forms of CRRT.

BackgroundSkin and soft tissue infections (SSTIs) are a leading cause for hospitalizations in the United States. Few studies have addressed the appropriateness of antibiotic therapy in the management of SSTIs without complicating factors. We aimed to determine the appropriateness of antibiotic treatment duration for hospitalized adult patients with uncomplicated SSTIs.MethodsThis was a retrospective analysis performed at two academic medical centers in Pittsburgh, Pennsylvania on patients aged 18 years and older with primary ICD-9 code for SSTIs admitted August 1st, 2014–March 31st, 2015. The primary outcome was the appropriateness of antibiotic treatment duration for uncomplicated SSTIs. Secondary objectives included the appropriateness of antibiotic agent spectrum, duration of inpatient length of stay (LOS), utilization of blood cultures and advanced imaging modalities, and re-hospitalization for SSTI within 30 days of discharge from the index admission.ResultsA total of 163 episodes were included in the cohort. The mean duration of total antibiotic therapy was 12.6 days. Appropriate duration was defined as receipt of total antibiotic duration of less than 10 days and occurred in 20.2% of patients. Twenty eight percent of patients received antibiotics for greater than 14 days. Seventy three (44.8%) patients received greater than 24 h of inappropriate extended spectrum gram-negative coverage; 65 (39.9%) received anaerobic coverage.ConclusionsIn the majority of patients, treatment duration was excessive. Inappropriate broad spectrum antibiotic selection was utilized with regularity for SSTIs without complicating factors. The management of uncomplicated SSTIs represents a significant opportunity for antimicrobial stewardship.

We conducted a pre-intervention/post-intervention study to assess the rate of healthcare-associated infections (HA-CDI) before and after the implementation of an antimicrobial stewardship program (ASP). Upon implementation of our ASP, the usage of targeted antimicrobials, including ceftriaxone, clindamycin, fluoroquinolones and carbapenem antibiotics, were significantly reduced. There was also a significant reduction in HA-CDI/1000 patient-days following ASP implementation (0.84 vs. 0.28; = 0.035).

Patients admitted from the community with a suspected central nervous system (CNS) infection require prompt diagnostic evaluation and correct antimicrobial treatment. A retrospective, multicenter, pre/post intervention study was performed to evaluate the impact that the BioFire® FilmArray® meningitis/encephalitis (ME) panel run in-house had on the clinical management of adult patients admitted from the community with a lumbar puncture (LP) performed for a suspected CNS infection. The primary outcome was the effect that this intervention had on herpes simplex virus (HSV) polymerase chain reaction (PCR) turnaround time (TAT). Secondary outcomes included the effect that this intervention had on antiviral days of therapy (DOT), total antimicrobial DOT, and hospital length of stay (LOS). A total of 81 and 79 patients were included in the pre-intervention and post-intervention cohorts, respectively. The median HSV PCR TAT was significantly longer in the pre-intervention group (85 vs. 4.1 h, p < 0.001). Total antiviral DOT was significantly greater in the pre-intervention group (3 vs. 1, p < 0.001), as was total antimicrobial DOT (7 vs. 5, p < 0.001). Pre-intervention hospital LOS was also significantly longer (6.6 vs. 4.4 days, p = 0.02). Implementing the ME panel in-house for adults undergoing an LP for a suspected community-onset CNS infection significantly reduced the HSV PCR TAT, antiviral DOT, total antimicrobial DOT, and hospital LOS.

Background Bloodstream infections (BSI) are a leading cause of morbidity and mortality in hospitalized patients. The IOAS (Improving Outcomes and Antimicrobial Stewardship) study seeks to evaluate the impact of the Accelerate PhenoTest® BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs. Methods This multicenter, quasi-experimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX testing, to evaluate the impact this technology has on patients with BSI. Laboratory and clinical data from hospitalized patients with BSI (excluding contaminants) were compared between two arms, one that underwent testing on AXDX (post-AXDX) and one that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) within 96 hours of blood culture positivity and 30-day mortality. Results A total of 854 patients with BSI (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared to the pre-AXDX arm (40.9 hours; P&lt;0.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 versus 13.9 hours; P&lt;0.0001) and first antimicrobial de-escalation (36.0 versus 27.2 hours; P=0.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX versus 6.0% post-AXDX), length of stay (7.0 pre-AXDX versus 6.5 days post-AXDX), and adverse drug events were not significantly different between arms. Length of stay was shorter in the post-AXDX arm (5.4 versus 6.4 days; P=0.03) among patients with Gram-negative bacteremia. Conclusions For BSIs, use of AXDX was associated with significant decreases in TTOT, first antimicrobial modification, and time to antimicrobial de-escalation.

We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P ‫؍‬ 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.A mong Gram-negative organisms, extensively drug-resistant (XDR) Acinetobacter baumannii is considered a serious threat to public health. As A. baumannii infections are associated with significant morbidity and mortality, the timely administration of effective broad-spectrum antibiotics is imperative (1). In recent years, increasing resistance among A. baumannii isolates has limited many therapy options, requiring the administration of empirical combination therapy for serious A. baumannii infections (2). In an attempt to select the most effective empirical antibiotic therapy, antimicrobial stewardship programs (ASPs) annually evaluate susceptibility based on institutional, unit-specific, or combination antibiograms. However, antibiograms are simply based on percent susceptibility and do not provide clinicians with additional aspects, including synergy or antagonism between agents. This presents significant limitations for ASPs in selecting optimal combination therapy for the treatment of A. baumannii infections.The comparison of specific antibiotic combinations identified in the literature provides ASPs with more definitive conclusions but does not address the heterogeneity of synergistic interactions of a specific combination against all isolates (3-6). Therefore, it may be more beneficial for ASPs to evaluate potential synergistic interactions in real time, particularly in critically ill patients infected with XDR A. baumannii. This study evaluated the use of a checkerboard platform to determine antibiotic combinations that are synergistic against XDR A. baumannii and compared the results to both time-kill assay results and clinical outcomes.We selected 76 unique XDR A. baumannii clinical isolates from our center between January 2009 and October 2013. Isolates were stored at Ϫ70°C and subcultured twice prior to testing. For the checkerboard assay, we identified the susceptibilities to amikacin (Crescent Chemical, Islandia, NY), colistin (MP Biomedical, Solon, OH), doripenem (TSZChem, Framingham, MA), minocycline (EMD Millipore, Darmstadt, Germany), and tigecycline (TSZChem, Framingham, MA) by microbroth dilution. Other susceptibilities were determined by the MicroScan system (Beckman Coulter, CA). The susceptibilities (percent) to the antibiotics tested were as follows: amikacin, 2/76 (3%); ampicillin-sulbactam, 2/76 (3%); cefepime, 0/76 (0%); ciprofloxacin, 0/76 (0%); do...

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