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Background In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in treatment decision-making. Methods A stepwise multivariable regression analysis was conducted to identify variables that were independently associated with day 28 all-cause mortality (ACM), favorable clinical response at early follow-up (EFU), and favorable microbiologic response at end of treatment (EOT). The analysis accounted for the number of baseline infecting pathogens and in vitro susceptibility to randomized treatment. Results Vasopressor use, renal impairment, bacteremia at baseline, and Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores ≥15 were associated with a greater risk of day 28 ACM. A favorable clinical response at EFU was associated with normal renal function, an APACHE II score Conclusions This analysis, which accounted for baseline pathogen susceptibility, validated well-recognized patient- and disease-related factors as independent predictors of clinical outcomes. These results lend further support to the noninferiority of IMI/REL to piperacillin/tazobactam and suggests that pathogen eradication may be more likely with IMI/REL.

Objective Respiratory support status is critical in understanding patient status, but electronic health record data are often scattered, incomplete, and contradictory. Further, there has been limited work on standardizing representations for respiratory support. The objective of this work was to (1) propose a practical terminology system for respiratory support methods; (2) develop (meta-)heuristics for constructing respiratory support episodes; and (3) evaluate the utility of respiratory support information for mortality prediction. Materials and Methods All analyses were performed using electronic health record data of COVID-19-tested, emergency department-admit, adult patients at a large, Midwestern healthcare system between March 1, 2020 and April 1, 2021. Logistic regression and XGBoost models were trained with and without respiratory support information, and performance metrics were compared. Importance of respiratory-support-based features was explored using absolute coefficient values for logistic regression and SHapley Additive exPlanations values for the XGBoost model. Results The proposed terminology system for respiratory support methods is as follows: Low-Flow Oxygen Therapy (LFOT), High-Flow Oxygen Therapy (HFOT), Non-Invasive Mechanical Ventilation (NIMV), Invasive Mechanical Ventilation (IMV), and ExtraCorporeal Membrane Oxygenation (ECMO). The addition of respiratory support information significantly improved mortality prediction (logistic regression area under receiver operating characteristic curve, median [IQR] from 0.855 [0.852—0.855] to 0.881 [0.876—0.884]; area under precision recall curve from 0.262 [0.245—0.268] to 0.319 [0.313—0.325], both P Conclusion Respiratory support information is critical in understanding patient status and can facilitate downstream analyses.

Objectives In the ASPECT-NP trial, ceftolozane/tazobactam was non-inferior to meropenem for treating nosocomial pneumonia; efficacy outcomes by causative pathogen were to be evaluated. Methods Mechanically ventilated participants with hospital-acquired/ventilator-associated bacterial pneumonia were randomized to 3 g ceftolozane/tazobactam (2 g ceftolozane/1 g tazobactam) q8h or 1 g meropenem q8h. Lower respiratory tract (LRT) cultures were obtained ≤36 h before first dose; pathogen identification and susceptibility were confirmed at a central laboratory. Prospective secondary per-pathogen endpoints included 28 day all-cause mortality (ACM), and clinical and microbiological response at test of cure (7–14 days after the end of therapy) in the microbiological ITT (mITT) population. Results The mITT population comprised 511 participants (264 ceftolozane/tazobactam, 247 meropenem). Baseline LRT pathogens included Klebsiella pneumoniae (34.6%), Pseudomonas aeruginosa (25.0%) and Escherichia coli (18.2%). Among baseline Enterobacterales isolates, 171/456 (37.5%) were ESBL positive. For Gram-negative baseline LRT pathogens, susceptibility rates were 87.0% for ceftolozane/tazobactam and 93.3% for meropenem. For Gram-negative pathogens, 28 day ACM [52/259 (20.1%) and 62/240 (25.8%)], clinical cure rates [157/259 (60.6%) and 137/240 (57.1%)] and microbiological eradication rates [189/259 (73.0%) and 163/240 (67.9%)] were comparable with ceftolozane/tazobactam and meropenem, respectively. Per-pathogen microbiological eradication for Enterobacterales [145/195 (74.4%) and 129/185 (69.7%); 95% CI: −4.37 to 13.58], ESBL-producing Enterobacterales [56/84 (66.7%) and 52/73 (71.2%); 95% CI: −18.56 to 9.93] and P. aeruginosa [47/63 (74.6%) and 41/65 (63.1%); 95% CI: −4.51 to 19.38], respectively, were also comparable. Conclusions In mechanically ventilated participants with nosocomial pneumonia owing to Gram-negative pathogens, ceftolozane/tazobactam was comparable with meropenem for per-pathogen 28 day ACM and clinical and microbiological response.

Background Synthetic data may provide a solution to researchers who wish to generate and share data in support of precision healthcare. Recent advances in data synthesis enable the creation and analysis of synthetic derivatives as if they were the original data; this process has significant advantages over data deidentification. Objectives To assess a big-data platform with data-synthesizing capabilities (MDClone Ltd., Beer Sheva, Israel) for its ability to produce data that can be used for research purposes while obviating privacy and confidentiality concerns. Methods We explored three use cases and tested the robustness of synthetic data by comparing the results of analyses using synthetic derivatives to analyses using the original data using traditional statistics, machine learning approaches, and spatial representations of the data. We designed these use cases with the purpose of conducting analyses at the observation level (Use Case 1), patient cohorts (Use Case 2), and population-level data (Use Case 3). Results For each use case, the results of the analyses were sufficiently statistically similar (P > 0.05) between the synthetic derivative and the real data to draw the same conclusions. Discussion and conclusion This article presents the results of each use case and outlines key considerations for the use of synthetic data, examining their role in clinical research for faster insights and improved data sharing in support of precision healthcare.

Background The prospective identification of patients at high risk for hospital-acquired/ventilator-associated bacterial pneumonia may improve clinical trial feasibility and foster antibacterial development. In a prior study conducted in the United States, clinical criteria were used to prospectively identify these patients; however, these criteria have not been applied in a European population. Methods Adults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of 7 European hospitals were prospectively enrolled from June 12 to December 27, 2017. We estimated the proportion of high-risk patients developing pneumonia according to US Food and Drug Administration guidance and a subset potentially eligible for antibacterial trial enrollment. We compared patient characteristics, treatment exposures, and pneumonia incidence in a European cohort and a previously described US cohort. Results Of 888 high-risk patients, 211/888 (24%) were treated for possible pneumonia, and 150/888 (17%) met the Food and Drug Administration definition for hospital-acquired/ventilator-associated bacterial pneumonia. A higher proportion of European patients treated for possible pneumonia met the pneumonia definition (150/211 [71%] vs 537/1464 [37%]; P Conclusions Clinical criteria prospectively identified high-risk patients with high rates of pneumonia in the European cohort. Despite higher rates of established risk factors and incident pneumonia, European patients were significantly less likely to receive antibiotics for possible pneumonia than US patients. Different treatment practices may contribute to lower rates of antibacterial trial enrollment in the United States.

The objective of this study was to directly compare the ability of commonly used early warning scores (EWS) for early identification and prediction of sepsis in the general ward setting. For general ward patients at a large, academic medical center between early-2012 and mid-2018, common EWS and patient acuity scoring systems were calculated from electronic health records (EHR) data for patients that both met and did not meet Sepsis-3 criteria. For identification of sepsis at index time, National Early Warning Score 2 (NEWS 2) had the highest performance (area under the receiver operating characteristic curve: 0.803 [95% confidence interval [CI]: 0.795–0.811], area under the precision recall curves: 0.130 [95% CI: 0.121–0.140]) followed NEWS, Modified Early Warning Score, and quick Sequential Organ Failure Assessment (qSOFA). Using validated thresholds, NEWS 2 also had the highest recall (0.758 [95% CI: 0.736–0.778]) but qSOFA had the highest specificity (0.950 [95% CI: 0.948–0.952]), positive predictive value (0.184 [95% CI: 0.169–0.198]), and F1 score (0.236 [95% CI: 0.220–0.253]). While NEWS 2 outperformed all other compared EWS and patient acuity scores, due to the low prevalence of sepsis, all scoring systems were prone to false positives (low positive predictive value without drastic sacrifices in sensitivity), thus leaving room for more computationally advanced approaches., Lay Summary Sepsis is a syndrome caused by an infection resulting in organ dysfunction and high rates of death, is implicated in nearly half of all inpatient deaths, and is the costliest inpatient condition in the United States. Early recognition and treatment are critical to the management of septic patients. As a result, over time, researchers have developed numerous early warning scores that use clinical measurements such as vital signs and lab results to generate a value that is indicative of the severity of illness and is predictive of clinical deterioration. Increasingly, these scores have been used as screening tools for sepsis management. To understand the comparative performance of these early warning scores in the general ward setting, electronic health records data were used to calculate the scores. Of the compared scores, the National Early Warning Score (NEWS 2) outperformed the rest. However, partially due to the low prevalence of sepsis in the general ward, even NEWS 2 was prone to false positives, highlighting the potential for improvement using more advanced computational methods.

Background Fast diagnostic tests providing earlier identification (ID) of pathogens, and antimicrobial susceptibility testing (AST) may reduce time to appropriate antimicrobial therapy (AAT), decrease mortality, and facilitate antimicrobial deescalation (ADE). Our objective was to determine the theoretical reduction in time to AAT and opportunities for ADE with Accelerate PhenoTM System (AXDX). Methods The prospective cohort (April 14, 2016 through June 1, 2017) was from the Barnes-Jewish Hospital, a 1250-bed academic center. Emergency department (ED) or intensive care unit (ICU) blood cultures Gram-stain positive for gram-negative bacilli (GNB) or yeast. AXDX was used in parallel with standard-of-care (SOC) diagnostics to determine differences in time to pathogen ID and AST. Theoretical opportunities for ADE from AXDX results were determined. Results In total, 429 blood cultures were screened, 153 meeting inclusion criteria: 110 on-panel GNB, 10 Candida glabrata, and 5 Candida albicans. For GNB SOC, median time from blood culture positivity to ID and AST were 28.2 and 52.1 h. Median time to ID and AST after AXDX initiation was 1.37 and 6.7 h for on-panel organisms. For on-panel Candida, time to ID was approximately 21 h faster with AXDX. ADE or AAT was theoretically possible with AXDX in 48.4%. Of on-panel organisms, 24.0% did not receive initial AAT. In-hospital mortality was 46.7% without initial AAT, and 11.6% with AAT. Coverage of AXDX was 75.3%, specificity 99.7%, positive predictive value (PPV) 96.0%, and negative predictive value (NPV) 97.6%. On-panel sensitivity was 91.5%, specificity 99.6%, PPV 96.0%, and NPV 99.0%. Conclusions AXDX provides more rapid ID and AST for GNB and ID for yeast than SOC. AXDX could potentially reduce time to AAT and facilitate ADE.

Background Multidrug-resistant organism (MDRO) infections are associated with high mortality and readmission rates. Infectious diseases (ID) consultation improves clinical outcomes for drug-resistant Staphylococcus aureus bloodstream infections. Our goal was to determine the association between ID consultation and mortality following various MDRO infections. Methods This study was conducted with a retrospective cohort (January 1, 2006–October 1, 2015) at an academic tertiary referral center. We identified patients with MDROs in a sterile site or bronchoalveolar lavage/bronchial wash culture. Mortality and readmissions within 1 year of index culture were identified, and the association of ID consultation with these outcomes was determined using Cox proportional hazards models with inverse weighting by the propensity score for ID consultation. Results A total of 4214 patients with MDRO infections were identified. ID consultation was significantly associated with reductions in 30-day and 1-year mortality for resistant S. aureus (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.63; and HR, 0.73, 95% CI, 0.61–0.86) and Enterobacteriaceae (HR, 0.41; 95% CI, 0.27–0.64; and HR, 0.74; 95% CI, 0.59–0.94), and 30-day mortality for polymicrobial infections (HR, 0.51; 95% CI, 0.31–0.86) but not Acinetobacter or Pseudomonas. For resistant Enterococcus, ID consultation was marginally associated with decreased 30-day mortality (HR, 0.81; 95% CI, 0.62–1.06). ID consultation was associated with reduced 30-day readmission for resistant Enterobacteriaceae. Conclusions ID consultation was associated with significant reductions in 30-day and 1-year mortality for resistant S. aureus and Enterobacteriaceae, and 30-day mortality for polymicrobial infections. There was no association between ID consultation and mortality for patients with resistant Pseudomonas, Acinetobacter, or Enterococcus, possibly due to small sample sizes. Our results suggest that ID consultation may be beneficial for patients with some MDRO infections.

Background NP is a frequent healthcare-acquired infection associated with high mortality; rising resistance rates among causative Gram-negative pathogens require new treatment options. In the randomized, controlled, double-blind, phase 3 ASPECT-NP trial, C/T (at double the initially approved dose) was noninferior to MEM for ventilated NP in both primary and key secondary endpoints. Here we evaluate the impact of prior and concomitant Gram-negative antibacterial therapy on outcomes in that trial. Methods Mechanically ventilated patients with ventilator-associated or hospital-acquired pneumonia were randomized 1:1 to 3 g C/T or 1 g MEM, both by 1-h IV infusion every 8 hours for 8–14 days. Patients could receive ≤24 hours of active antibacterial therapy within ≤72 hours prior to first dose; longer durations were permitted in case of prior treatment failure (i.e., signs and/or symptoms of the current episode of ventilated NP persisted/worsened despite ≥48 hours of treatment). At sites with MEM-resistant Pseudomonas aeruginosa rates ≥15%, patients could optionally receive up to 72 h of adjunctive empiric aminoglycoside (amikacin was recommended) until study drug susceptibility was confirmed. Primary and key secondary endpoints, respectively, were 28-d all-cause mortality and clinical response at test of cure (TOC; 7–14 days after the end of therapy) in the intent to treat (ITT) population (all randomized patients). Results In the C/T arm, 285/362 (79%) ITT patients received prior systemic Gram-negative therapy and 103/362 (28%) received adjunctive aminoglycoside, compared with 288/364 (79%) and 112/364 (31%) patients, respectively, in the MEM arm. In the microbiologic ITT population, causative pathogens in patients failing prior therapy at the time of enrollment (C/T 15%, MEM 11%) were mainly Klebsiella spp (33%), P. aeruginosa (17%), Escherichia coli (14%), and Acinetobacter baumannii (8%). Mortality and cure rates were comparable between C/T and MEM regardless of receipt of prior systemic or adjunctive Gram-negative therapy (table). Conclusion Prior and adjunctive Gram-negative antibacterial therapy did not affect the relative efficacy of C/T (at the 3-g dose) vs. MEM in these high-risk patients with Gram-negative ventilated NP. Disclosures All authors: No reported disclosures.

Background One aim of antimicrobial stewardship programs is to combat climbing rates of antibiotic resistance. Typically coordinated by Infectious Diseases (ID) physicians, such programs have decreased costs, resistance rates and secondary infections. A point of contention is whether ID or Critical Care (CC) physicians should manage the antibiotics prescribed to critically ill patients in the Intensive Care Unit (ICU). We surveyed ID and CC physicians regarding their perspectives on ICU antimicrobial stewardship and collaborations. Methods In 2017, CC and ID fellows and attendings completed an online survey that included 17 Likert-scaled items (1 = strongly disagree to 5 = strongly agree) measuring views on ICU antibiotic stewardship. Principal components analysis (PCA) was used for data reduction. Multivariable linear regression models explored variables associated with outcomes measuring physicians’ views on which specialty should guide antibiotic stewardship and the value of clinical collaborations in the ICU. Results Of 334 physicians, 71% were attendings (vs. fellows) and 61% were ID (vs. CC) specialists. From the PCA, 3 factors emerged measuring views about: (1) the specialty that should serve as ICU antibiotic stewards (Cronbach’s α = 0.71; higher scores indicate ID physicians should be stewards); (2) ICU clinical collaborations (α = 0.60; higher scores indicate greater value of collaboration); and (3) ICU decision-making insecurity (α = 0.45; higher scores indicate greater insecurity). In the regression models (n = 309), CC physicians and those placing lower value on ICU collaborations reported greater agreement that ID physicians should be the primary ICU stewards; women and physicians reporting greater ICU decision-making insecurity and less agreement that ID physicians should be ICU antibiotic stewards reported greater value of clinical collaborations. Conclusion CC physicians favor ID specialists to assume ICU antibiotic stewardship. Disclosures All authors: No reported disclosures.

Background: Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. Methods: A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). Results: Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. Conclusions: The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical outcomes.

Background Resistant organisms (ROs) are increasingly implicated in pneumonia in patients presenting to the emergency department (ED). The concept of healthcare-associated pneumonia (HCAP) exists to help identify patients infected with ROs but may be overly broad. We sought to validate a previously developed score for determining the risk for an RO and to compare it with the HCAP definition. Methods We evaluated adult patients admitted via the ED with bacterial pneumonia (January-December 2010). We defined methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and extended-spectrum β-lactamases as ROs. The risk score was as follows: 4, recent hospitalization; 3, nursing home; 2, chronic hemodialysis; 1, critically ill. We evaluated the screening value of the score and of HCAP by determining their areas under the receiver-operating characteristic (AUROC) curves for predicting ROs. Results The cohort included 977 patients, and ROs were isolated in 46.7%. The most common organisms included MRSA (22.7%), P. aeruginosa (19.1%), and Streptococcus pneumoniae (19.1%). The risk score was higher in those with an RO (median score, 4 vs 1; P 0 had a high negative predictive value (84.5%) and could lead to fewer patients unnecessarily receiving broad-spectrum antibiotics. Conclusions ROs are common in patients presenting to the ED with pneumonia. A simple clinical risk score performs moderately well at classifying patients regarding their risk for an RO.

The emerging problem of antibiotic resistance, especially among Gram-negative bacteria (GNB), has become a serious threat to global public health. Very few new antibacterial classes with activity against antibiotic-resistant GNB have been brought to market. Renewed and growing attention to the development of novel compounds targeting antibiotic-resistant GNB, as well as a better understanding of strategies aimed at preventing the spread of resistant bacterial strains and preserving the efficacy of existing antibiotic agents, has occurred. The Gram-Negative Resistance Summit convened national opinion leaders for the purpose of analyzing current literature, epidemiologic trends, clinical trial data, therapeutic options, and treatment guidelines related to the management of antibiotic-resistant GNB infections. After an in-depth analysis, the Summit investigators were surveyed with regard to 4 clinical practice statements. The results then were compared with the same survey completed by 138 infectious disease and critical care physicians and are the basis of this article.

Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection and the leading cause of mortality attributable to these critical infections [ 1– 3]. Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is now a major cause of HAP [ 4– 6]. Rates of clinical failure in patients with HAP due to MRSA are high [ 7, 8]. Currently, only vancomycin and linezolid are recommended for treatment of HAP due to MRSA [ 9]. Results from recent pneumonia trials with new antibiotics active against MRSA have not been encouraging [ 10– 12]. Therefore, additional antistaphylococcal agents for treatment of HAP are urgently needed. Telavancin is a lipoglycopeptide antibacterial agent exhibiting potent, concentration-dependent bactericidal effects via a dual mechanism of action that combines inhibition of cell wall synthesis and disruption of membrane barrier function [ 13– 15]. In vitro, telavancin is rapidly bactericidal against clinically important gram-positive bacteria, including MRSA, vancomycin-intermediate S. aureus, and penicillin-resistant S. pneumoniae [ 13, 16, 17]. Telavancin penetrates well into the epithelial lining fluid and alveolar macrophages of healthy subjects, achieving concentrations up to 8-fold and 85-fold, respectively, above telavancin's minimum inhibitory concentration (MIC) for 90% (MIC90) of MRSA strains (.5 μg/mL) [ 16, 18]. Unlike daptomycin (a cyclic lipopeptide), telavancin remains active in vitro in the presence of pulmonary surfactant [ 16]. Telavancin is approved in the United States and Canada for the treatment of adult patients with complicated skin and skin-structure infections due to susceptible gram-positive pathogens. The current studies were designed to assess the clinical efficacy and safety of telavancin compared with vancomycin in the treatment of HAP due to gram-positive organisms, with a focus on infections due to MRSA. Partial results of these studies have been previously reported.

During the Health Care-Associated Pneumonia Summit conducted in June 2007, it was found that there is a need for educational efforts in several areas of health care-associated infections (HAI) that extend beyond pneumonia. This supplement to Clinical Infectious Diseases represents the proceedings of the HAI Summit, a diverse panel of clinical investigators whose goal was to assess the quality of evidence regarding issues surrounding HAI and to discuss potential implications for its diagnosis and treatment in the future.

Vancomycin is effective against methicillin-resistant Staphylococcus aureus and has been widely used in the past few years. However, several recent reports have highlighted the limitations of vancomycin, and its role in the management of serious infections is now being reconsidered. Vancomycin treatment failure rates are associated with an increase in the minimum inhibitory concentration as well as a decrease in the rate of bacterial killing. The intrinsic limitations of vancomycin also include poor tissue penetration, particularly in the lung; relatively slow bacterial killing; and the potential for toxicity. In addition, intermediate-level vancomycin resistance has emerged among staphylococci, as have rare cases of fully resistant strains. Because of these problems, when using vancomycin, it is probably prudent to carefully establish the diagnosis, test for antimicrobial susceptibility, and monitor serum trough concentrations to ensure adequate dosing.

Objectives To compare outcomes in patients with Staphylococcus aureus bacteraemia treated with linezolid with those of vancomycin-treated patients. Methods We pooled and analysed five randomized studies comparing linezolid with vancomycin, focusing on the 144 adults with S. aureus bacteraemia, which was secondary in >70% of patients. Efficacy variables were clinical cure of primary infection, microbiological success (eradication of S. aureus from blood or presumed eradication based on clinical cure of primary infection), survival, and outcome predictors identified by multivariate logistic regression. Results Of 99 clinically evaluable patients, primary infection was cured in 28 (55%) of 51 linezolid recipients and 25 (52%) of 48 vancomycin recipients [odds ratio (OR) for cure with linezolid versus vancomycin, 1.12; 95% confidence interval (CI), 0.51-2.47]. There were no between-group differences in the meta-analysis (OR, 1.16; 95% CI, 0.5-2.65). Of 53 evaluable patients with methicillin-resistant S. aureus (MRSA) bacteraemia, clinical cure occurred in 14 (56%) of 25 linezolid recipients and 13 (46%) of 28 vancomycin recipients (OR, 1.47; 95% CI, 0.50-4.34). Microbiological success occurred in 41 (69%) of 59 linezolid recipients and 41 (73%) of 56 vancomycin recipients (OR, 0.83; 95% CI, 0.37-1.87). Fifty-five (74%) of 74 linezolid recipients survived versus 52 (74%) of 70 vancomycin recipients (OR, 1.00; 95% CI, 0.47-2.12). In the multivariate analysis, treatment group was not a significant predictor of clinical cure or survival. Conclusions Linezolid was associated with outcomes that were not inferior to those of vancomycin in patients with secondary S. aureus bacteraemia.

Successful treatment of patients with nosocomial pneumonia depends primarily on providing adequate initial antibiotic treatment in a timely manner, because an inappropriate course is closely associated with increased mortality. Gram-negative bacteria are commonly responsible for nosocomial pneumonia, and the increasing prevalence of drug resistance among these bacteria complicates decision making with regard to treatment with antibiotics. Infections due to Pseudomonas aeruginosa are particularly problematic because of their intrinsic resistance to multiple classes of antibiotics and their ability to acquire adaptive resistance during a therapeutic course. Numerous strategies, including the use of combination therapy followed by de-escalation of antibiotics, have shown promise in the treatment of these serious infections. However, future success in treating nosocomial infections depends on the appropriate and responsible use of antibiotics in the intensive care unit, to ensure that the antibiotics available today maintain their effectiveness in the future.

Although quinolones are often used to treat nosocomial pneumonia (NP), there have been few trials documenting their efficacy in treating NP. Given the growing use of quinolones and issues regarding resistance, we conducted a meta-analysis of all trials of quinolones for treatment of NP. We identified 5 randomized trials comparing quinolones with other agents used to treat NP. The studies varied in both quality and sample size and included a total of nearly 1200 subjects. Four of the 5 trials used ciprofloxacin, administered every 8 h, whereas the fifth used levofloxacin administered daily. In 3 trials, the comparator agent was imipenem-cilistatin, whereas, in 2 trials, ceftazadime was the comparator agent. The efficacy of quinolones and comparator antibiotics was similar, with a pooled odds ratio for clinical cure of 1.12 (95% confidence interval, 0.80-1.55). Neither microbiological eradication rates nor mortality rates varied on the basis of antimicrobial selection.

Infection-control recommendations include the use of gowns and gloves to prevent horizontal transmission of vancomycin-resistant enterococci (VRE). This study sought to determine whether the use of a gown and gloves gives greater protection than glove use alone against VRE transmission in a medical intensive care unit (MICU). From 1 July 1997 through 30 June 1998 and from 1 July 1999 through 31 December 1999, health care personnel and visitors were required to don gloves and gowns upon entry into rooms where there were patients infected with nosocomial pathogens. From 1 July 1998 through 30 June 1999, only gloves were required under these same circumstances. During the gown period, 59 patients acquired VRE (9.1 cases per 1000 MICU-days), and 73 patients acquired VRE during the no-gown period (19.6 cases per 1000 MICU-days; P

Background The association between the administration of inappropriate empiric antibiotic treatment (IEA) and an increased risk of hospital mortality has been consistently reported. This study explores pre-infection risk factors for IEA in patients with Gram-negative (GN) sterile site infections complicated by sepsis or septic shock. Methods Retrospective cohort study at Barnes-Jewish Hospital (2010–2015). Risk factors including history of hospitalization, receipt of intravenous antipseudomonal antibiotics, and isolation of GN organisms 90 days prior to admission were collected. Process of care variables assessed included ICU admission, durations of mechanical ventilation, central venous catheter, and urinary catheter insertion, and antibiotic days prior to isolation of a GN pathogen(s). IEA was defined as receipt of antibiotic therapy that lacked in vitro activity against the identified pathogen(s) within the 24 hours of the culture being obtained. Multivariable logistic regression analysis (MVLRA) risk factor modeling that included IEA as the dependent outcome variable was conducted. Results 855 consecutive patients with first episode sepsis or septic shock were included. Compared with patients receiving appropriate empiric therapy (n = 715), variables significantly associated with IEA (n = 140) within 90 days prior to admission included recent hospitalization (23.1% v. 34.3%, P = 0.005), mean days of meropenem (0 v. 2.1, P = 0.010) and piperacillin-tazobactam (0 v. 1.6, P

Scheduled rotation of treatment of gram-negative antimicrobial agents has been associated with reduction of serious gram-negative infections. The impact of this practice on other nosocomial infections has not been assessed. The purpose of this study was to determine if scheduled antimicrobial rotation reduced rates of acquisition of enteric vancomycin-resistant enterococci (VRE) among 740 patients admitted to an intensive care unit (ICU). The preferred gram-negative agent was ceftazidime during rotation 1 and ciprofloxacin during rotation 2. Unadjusted VRE acquisition rates were 8.5 cases per 1000 ICU days and 11.7 cases per 1000 ICU days during rotations 1 and 2, respectively (P

Inadequate antimicrobial treatment, generally defined as microbiological documentation of an infection that is not being effectively treated, is an important factor in the emergence of infections due to antibiotic-resistant bacteria. Factors that contribute to inadequate antimicrobial treatment of hospitalized patients include prior antibiotic exposure, use of broad-spectrum antibiotics, prolonged length of stay, prolonged mechanical ventilation, and presence of invasive devices. Strategies to minimize inadequate treatment include consulting an infectious disease specialist, using antibiotic practice guidelines, and identifying quicker methods of microbiological identification. In addition, clinicians should determine the prevailing pathogens that account for the community-acquired and nosocomial infections identified in their hospitals. Clinicians can improve antimicrobial treatment by using empirical combination antibiotic therapy based on individual patient characteristics and the predominant bacterial flora and their antibiotic susceptibility profiles. This broad-spectrum therapy can then be narrowed when initial culture results are received. Further study evaluating the use of antibiotic practice guidelines and strategies to reduce inadequate treatment is necessary to determine their impact on patient outcomes.

There is a general consensus that antimicrobial resistance in the hospital setting has emerged as an important variable that influences patient outcomes and overall use of resources [ 1-3]. Hospitals worldwide are faced with increasingly rapid emergence and spread of antibiotic-resistant bacteria. Antibiotic-resistant strains of both gram-negative bacilli and gram-positive bacteria are reported to be important causes of hospital-acquired infection, including ventilator-associated pneumonia (VAP) [4, 5]. In many cases, few antimicrobial agents remain available for effective treatment, particularly with regard to methicillin-resistant and vancomycin-resistant Staphylococcus aureus and gram-negative bacteria that produce extended-spectrum 3-lactamases and that have resistance to multiple other antibiotics [6-8]. One of the consequences of a greater prevalence of antimicrobial resistance is an increased recognition of inadequate

A patient with bilateral chylous effusions and chylous ascites resulting from mediastinal and periaortic radiation for Hodgkin's lymphoma is described. The chylothoraces were resistant to medical treatment as well as to surgical pleurectomy. The patient's medical condition worsened due to progression of the chylous effusions and an episode of catheter-related bacteremia complicated by respiratory failure requiring mechanical ventilation. While receiving mechanical ventilation, the patient was found to have hypothyroidism and was subsequently begun on thyroid hormone replacement therapy. Within 1 week, the chylous drainage from the pleural spaces dramatically decreased and eventually resolved. Eighteen months after beginning thyroid hormone replacement therapy, the patient continues to do well without recurrence of the chylous effusions.

Challenges in the treatment of serious bacterial infections include the requirement for prompt initiation of appropriate antimicrobial therapy (therapy that is correct on the basis of available clinical, pharmacological, and microbiological data) to minimize morbidity and mortality. Delaying the initiation of appropriate therapy or initiating inappropriate therapy has been shown, in numerous studies of a variety of serious bacterial infections, to be associated with poor outcomes [1-3]. Challenges in the determination of appropriate antimicrobial therapy for serious bacterial infections include an increasing incidence of antimicrobial-resistant pathogens [4-11]. In addition, for most cases of serious bacterial infection, there is little time to determine the right treatment, as time to initiation of effective therapy is a strong predictor of mortality. Thus, initial treatment must be empirical; that is, it must be implemented before pathogen culture and susceptibility results can be obtained.