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ObjectiveTo compare clinical outcomes in children with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) who were managed before and after implementation of an evidence-based guideline (EBG).MethodsA management algorithm for MAS-HLH was developed at our institution based on literature review, expert opinion, and consensus building across multiple pediatric subspecialties. An electronic medical record search retrospectively identified hospitalized patients with MAS-HLH in the pre-EBG (October 15, 2015, to December 4, 2017) and post-EBG (January 1, 2018, to January 21, 2020) time periods. Predetermined outcome metrics were evaluated in the 2 cohorts.ResultsAfter the EBG launch, 57 children were identified by house staff as potential patients with MAS-HLH, and rheumatology was consulted for management. Ultimately, 17 patients were diagnosed with MAS-HLH by the treating team. Of these, 59% met HLH 2004 criteria, and 94% met 2016 classification criteria for MAS complicating systemic juvenile idiopathic arthritis. There was a statistically significant reduction in mortality from 50% before implementation of the EBG to 6% in the post-EBG cohort (P = 0.02). There was a significant improvement in time to 50% reduction in C-reactive protein level in the post-EBG vs pre-EBG cohorts (log-rank P < 0.01). There were trends toward faster time to MAS-HLH diagnosis, faster initiation of immunosuppressive therapy, shorter length of hospital stay, and more rapid normalization of MAS-HLH–related biomarkers in the patients post-EBG.ConclusionWhile the observed improvements may be partially attributed to advances in treatment of MAS-HLH that have accumulated over time, this analysis also suggests that a multidisciplinary treatment pathway for MAS-HLH contributed meaningfully to favorable patient outcomes.

The purpose of this document is to highlight practical recommendations to assist acute care hospitals to prioritize and implement strategies to prevent ventilator-associated pneumonia (VAP), ventilator-associated events (VAE), and non-ventilator hospital-acquired pneumonia (NV-HAP) in adults, children, and neonates. This document updates the Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology (SHEA), and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America, the American Hospital Association, the Association for Professionals in Infection Control and Epidemiology, and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

Acute bacterial infections are often treated empirically, with the choice of antibiotic therapy updated during treatment. The effects of such rapid antibiotic switching on the evolution of antibiotic resistance in individual patients are poorly understood. Here we find that low-frequency antibiotic resistance mutations emerge, contract, and even go to extinction within days of changes in therapy. We analyzed Pseudomonas aeruginosa populations in sputum samples collected serially from 7 mechanically ventilated patients at the onset of respiratory infection. Combining short- and long-read sequencing and resistance phenotyping of 420 isolates revealed that while new infections are near-clonal, reflecting a recent colonization bottleneck, resistance mutations could emerge at low frequencies within days of therapy. We then measured the in vivo frequencies of select resistance mutations in intact sputum samples with resistance-targeted deep amplicon sequencing (RETRA-Seq), which revealed that rare resistance mutations not detected by clinically used culture-based methods can increase by nearly 40-fold over 5–12 days in response to antibiotic changes. Conversely, mutations conferring resistance to antibiotics not administered diminish and even go to extinction. Our results underscore how therapy choice shapes the dynamics of low-frequency resistance mutations at short time scales, and the findings provide a possibility for driving resistance mutations to extinction during early stages of infection by designing patient-specific antibiotic cycling strategies informed by deep genomic surveillance.

Bacteria in the Burkholderia cepacia complex (BCC) are significant pathogens for people with cystic fibrosis (CF) and are often extensively antibiotic resistant. Here, we assess the impacts of clinically observed mutations in fixL, which encodes the sensor histidine kinase FixL. FixL along with FixJ compose a two-component system that regulates multiple phenotypes. Mutations in fixL across two species, B. dolosa and B. multivorans, have shown evidence of positive selection during chronic lung infection in CF. Herein, we find that BCC carrying the conserved, ancestral fixL sequence have lower survival in macrophages and in murine pneumonia models than mutants carrying evolved fixL sequences associated with clinical decline in CF patients. In vitro phosphotransfer experiments found that one evolved FixL protein, W439S, has a reduced ability to autophosphorylate and phosphorylate FixJ, while LacZ reporter experiments demonstrate that B. dolosa carrying evolved fixL alleles has reduced fix pathway activity. Interestingly, B. dolosa carrying evolved fixL alleles was less fit in a soil assay than those strains carrying the ancestral allele, demonstrating that increased survival of these variants in macrophages and the murine lung comes at a potential expense in their environmental reservoir. Thus, modulation of the two-component system encoded by fixLJ by point mutations is one mechanism that allows BCC to adapt to the host infection environment.

Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics.To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes.This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes.A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative).The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock.Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation.Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

ObjectiveTo assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).DesignDescriptive retrospective cohort with nested case-control study.SettingPediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.PatientsChildren≤18 years ventilated for≥1 calendar day.MethodsWe identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.ResultsAmong 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.ConclusionsAntimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.

Isoflurane and sevoflurane are volatile anesthetics (VA) widely used in clinical practice to provide general anesthesia. We and others have previously shown that VAs have immunomodulatory effects and may have a significant impact on the progression of disease states. Flagellin is a component of Gram negative bacteria and plays a significant role in the pathophysiology of bacterial pneumonia through its binding to Toll-like Receptor 5 (TLR5). Our results showed that VAs, not an intravenous anesthetic, significantly attenuated the activation of TLR5 and the release of the neutrophil chemoattractant IL-8 from lung epithelial cells. Furthermore, flagellin-induced lung injury was significantly attenuated by VAs by inhibiting neutrophil migration to the bronchoalveolar space. The lungs of cystic fibrosis (CF) patients are highly colonized by Pseudomonas aeruginosa, which causes inflammation. The retrospective study of oxygenation in patients with CF who had received VA versus intravenous anesthesia suggested that VAs might have the protective effect for gas exchange. To understand the interaction between VAs and TLR5, a docking simulation was performed, which indicated that isoflurane and sevoflurane docked into the binding interphase between TLR5 and flagellin.

Background Infection is a major complication following cerebral spinal fluid (CSF) diversion procedures for hydrocephalus. However, pediatric risk factors for surgical site infection (SSI) are currently not well defined. Because a SSI prevention bundle is increasingly introduced, the purpose of this study was to evaluate risk factors associated with SSIs following CSF diversion surgeries following a SSI bundle at a single quaternary care pediatric hospital. Methods We performed a retrospective cohort study of patients undergoing CSF diversion procedures from 2017 to 2019. SSIs were identified prospectively through continuous surveillance. We performed unadjusted logistic regression analyses and univariate analyses to determine an association between SSIs and patient demographics, comorbidities and perioperative factors to identify independent risk factors for SSI. Results We identified a total of 558 CSF diversion procedures with an overall SSI rate of 3.4%. The SSI rates for shunt, external ventricular drain (EVD) placement, and endoscopic third ventriculostomy (ETV) were 4.3, 6.9 and 0%, respectively. Among 323 shunt operations, receipt of clindamycin as perioperative prophylaxis and presence of cardiac disease were significantly associated with SSI (O.R. 4.99, 95% C.I. 1.27–19.70, p = 0.02 for the former, and O.R. 7.19, 95% C.I. 1.35–38.35, p = 0.02 for the latter). No risk factors for SSI were identified among 72 EVD procedures. Conclusion We identified receipt of clindamycin as perioperative prophylaxis and the presence of cardiac disease as risk factors for SSI in shunt procedures. Cefazolin is recommended as a standard antibiotic for perioperative prophylaxis. Knowing that unsubstantiated beta-lactam allergy label is a significant medical problem, efforts should be made to clarify beta-lactam allergy status to maximize the number of patients who can receive cefazolin for prophylaxis before shunt placement. Further research is needed to elucidate the mechanism by which cardiac disease may increase SSI risk after shunt procedures.

Structured Summary Background Although surgical site infections (SSIs) remain a significant health care issue, a limited number of studies have analyzed risk factors for SSIs in children, particularly the role of intraoperative anesthetic management. Pediatric patients are less likely to have major adult risk factors for SSIs such as smoking and diabetes. Thus children may be more suitable as a cohort for examining the role of intraoperative anesthetics in SSIs. Aim We examined an association between SSI incidence and anesthetic management in children who underwent elective intestinal surgery in a single institution. Methods We performed a retrospective study of 621 patients who underwent elective intestinal surgery under general anesthesia between January 2017 and September 2019, with primary outcome as the incidence of SSIs. We compared patients who were dichotomized in accordance with the median of the sevoflurane dose. We used propensity score (PS) pairwise matching of these patients to avoid selection biases. PS matching yielded 204 pairs of patients. Results We found that higher doses of sevoflurane were associated with a higher incidence of SSIs (9.8% versus 3.9%, P = 0.019). We adjusted for intraoperative factors that were not included in the PS adjustment factors, and multivariate regression analysis after PS matching showed compatible results (odds ratio: 2.58, 95% confidence interval: 1.11-6.04, P = 0.028). Conclusions Higher doses of sevoflurane are associated with increased odds of SSIs after pediatric elective intestinal surgery. A randomized controlled study of volatile anesthetic-based versus intravenous anesthetic-based anesthesia will be needed to further determine the role of anesthetic drugs in SSI risk.

Objective:To institute facility-wide Kamishibai card (K-card) rounding for central venous catheter (CVC) maintenance bundle education and adherence and to evaluate its impact on bundle reliability and central-line–associated bloodstream infection (CLABSI) rates.Design:Quality improvement project.Setting:Inpatient units at a large, academic freestanding children’s hospital.Participants:Data for inpatients with a CVC in place for ≥1 day between November 1, 2017 and October 31, 2018 were included.Intervention:A K-card was developed based on 7 core elements in our CVC maintenance bundle. During monthly audits, auditors used the K-cards to ask bedside nurses standardized questions and to conduct medical record documentation reviews in real time. Adherence to every bundle element was required for the audit to be considered “adherent.” We recorded bundle reliability prospectively, and we compared reliability and CLABSI rates at baseline and 1 year after the intervention.Results:During the study period, 2,321 K-card audits were performed for 1,051 unique patients. Overall maintenance bundle reliability increased significantly from 43% at baseline to 78% at 12 months after implementation (P < .001). The hospital-wide CLABSI rate decreased from 1.35 during the 12-month baseline period to 1.17 during the 12-month intervention period, but the change was not statistically significant (incidence rate ratio [IRR], 0.87; 95% confidence interval [CI], 0.60–1.24; P = .41).Conclusions:Hospital-wide CVC K-card rounding facilitated standardized data collection, discussion of reliability, and real-time feedback to nurses. Maintenance bundle reliability increased after implementation, accompanied by a nonsignificant decrease in the CLABSI rate.

Background Critically ill infants with congenital heart disease (CHD) are often prescribed stress ulcer prophylaxis (SUP) to prevent upper gastrointestinal bleeding, despite the low incidence of stress ulcers and limited data on the safety and efficacy of SUP in infants. Recently, SUP has been associated with an increased incidence of hospital-acquired infections, community-acquired pneumonia, and necrotizing enterocolitis. The objective of this pilot study is to investigate the feasibility of performing a randomized controlled trial to assess the safety and efficacy of withholding SUP in infants with congenital heart disease admitted to the cardiac intensive care unit. Methods A single center, prospective, double-blinded, randomized placebo-controlled pilot feasibility trial will be performed in infants with CHD admitted to the cardiac intensive care unit and anticipated to require respiratory support for > 24 h. Patients will be randomized to receive a histamine-2 receptor antagonist (H2RA) or placebo until they are discontinued from respiratory support. Randomization will be performed within 2 strata defined by admission type (medical or surgical) and age (neonate, age Discussion Routine use of SUP to prevent upper gastrointestinal bleeding in infants is controversial due to a low incidence of bleeding events and concern for adverse effects. The role of SUP in infants with CHD has not been examined, and there is equipoise on the risks and benefits of withholding this therapy. In addition, this therapy has been discontinued in other neonatal populations due to the concern for hospital-acquired infections and necrotizing enterocolitis. Furthermore, exploring changes to the microbiome after exposure to SUP may highlight the mechanisms by which SUP impacts potential microbial dysbiosis of the gut and its association with hospital-acquired infections. Assessment of the feasibility of a trial of withholding SUP in critically ill infants with CHD will facilitate planning of a larger multicenter trial of safety and efficacy of SUP in this vulnerable population. Trial registration ClinicalTrials.gov, NCT03667703. Registered 12 September 2018, https://clinicaltrials.gov/ct2/show/NCT03667703?term=SUPPRESS+CHD&draw=2&rank=1. All WHO Trial Registration Data Set Criteria are met in this manuscript.

OBJECTIVEAdult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.DESIGNRetrospective cohortSETTINGPediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitalsPATIENTSPatients ≤18 years old ventilated for ≥1 dayMETHODSWe identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.RESULTSIn total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.CONCLUSIONSWe propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.Infect Control Hosp Epidemiol 2017;38:327–333

Probiotics are routinely administered to hospitalized patients for many potential indications

A newly proposed surveillance definition for ventilator-associated conditions among neonatal and pediatric patients has been associated with increased morbidity and mortality among ventilated patients in cardiac ICU, neonatal ICU, and PICU. This study aimed to identify potential risk factors associated with pediatric ventilator-associated conditions.Retrospective cohort.Six U.S. hospitals PATIENTS:: Children less than or equal to 18 years old ventilated for greater than or equal to 1 day.None.We identified children with pediatric ventilator-associated conditions and matched them to children without ventilator-associated conditions. Medical records were reviewed for comorbidities and acute care factors. We used bivariate and multivariate conditional logistic regression models to identify factors associated with ventilator-associated conditions. We studied 192 pairs of ventilator-associated conditions cases and matched controls (113 in the PICU and cardiac ICU combined; 79 in the neonatal ICU). In the PICU/cardiac ICU, potential risk factors for ventilator-associated conditions included neuromuscular blockade (odds ratio, 2.29; 95% CI, 1.08-4.87), positive fluid balance (highest quartile compared with the lowest, odds ratio, 7.76; 95% CI, 2.10-28.6), and blood product use (odds ratio, 1.52; 95% CI, 0.70-3.28). Weaning from sedation (i.e., decreasing sedation) or interruption of sedation may be protective (odds ratio, 0.44; 95% CI, 0.18-1.11). In the neonatal ICU, potential risk factors included blood product use (odds ratio, 2.99; 95% CI, 1.02-8.78), neuromuscular blockade use (odds ratio, 3.96; 95% CI, 0.93-16.9), and recent surgical procedures (odds ratio, 2.19; 95% CI, 0.77-6.28). Weaning or interrupting sedation was protective (odds ratio, 0.07; 95% CI, 0.01-0.79).In mechanically ventilated neonates and children, we identified several possible risk factors associated with ventilator-associated conditions. Next steps include studying propensity-matched cohorts and prospectively testing whether changes in sedation management, transfusion thresholds, and fluid management can decrease pediatric ventilator-associated conditions rates and improve patient outcomes.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent pathogen in patients with cystic fibrosis (CF) associated with increased morbidity. Ceftaroline fosamil is an intravenous (IV) cephalosporin with activity against MRSA. There are minimal data regarding dosing in the CF population. The objective of this study was to determine the pharmacokinetic and pharmacodynamic profile of IV ceftaroline in patients with CF. Methods We conducted a single-center prospective study of children and young adults with CF receiving ceftaroline (15mg/kg IV up to 600mg every 8h) as part of treatment for a CF pulmonary exacerbation between June 2016 and April 2017. Seven patients were enrolled for a total of 10 treatment courses. For each treatment course, up to 8 plasma samples were assayed for ceftaroline using ultra-high performance liquid chromatography with mass spectrometry. Maximum plasma concentration, systemic clearance, and elimination half-life were calculated. The area under the curve (AUC) above the minimum inhibitory concentration (MIC) and the percent time above the MIC (%fT>MIC) were determined for each subject using MICs of 0.5, 1, and 2μg/mL and the measured MIC if available. Results The mean (SD) age for the 7 patients was 20.3 (8.0) years. Mean (SD) maximum plasma concentration of ceftaroline was 22.7 (9.6) μg/mL, systemic clearance 7.9 (3.3) L/h, and half-life 1.1 (0.4) hours. Using a MIC of 1 μg/mL, accepted as the MIC 90 of MRSA isolates, AUC above MIC mean (SD) was 53.6 (19.5) μg·h/mL, mean (SD) %fT>MIC was 75.7 (10.4), and all subjects had >60%fT>MIC. Conclusions In this cohort of CF patients, mean ceftaroline half-life was 1.1h, which is notably lower than the general population. The dosing regimen studied, which exceeds the recommended dosing in the non-CF population, was adequate to achieve >60% time above the MIC in all patients.

Objectives To determine whether incident detection of Stenotrophomonas maltophilia (SM) in patients with cystic fibrosis (CF) is associated with accelerated lung function decline and increased hospitalizations and to determine whether this effect is more pronounced in individuals with subsequent chronic infection. Methods We performed a longitudinal, retrospective single-center, pre-post study of 88 patients with CF, ages 6–51 years, with first positive respiratory culture for SM between 2008 and 2014. Rate of decline in FEV1 and hospitalization rates prior to and following incident SM infection were analyzed using segmented regression analysis of interrupted time series. Results Mean (SD) age was 17.4 (9.2) years and the mean (SD) FEV1 % predicted at acquisition was 90.0% (25.2). A total of 44% developed chronic SM infection. In regression analysis adjusted for clinical and demographic factors, there was worsening of the mean annual decline in FEV1 % predicted from −1.79 (95%CI: −2.43, −1.15) pre-acquisition to −2.14 (95%CI: −2.61, −1.67) post-acquisition (P = 0.005). A significant change was observed in those with either subsequent intermittent or chronic infection. The mean annual hospitalization rate increased significantly in the subgroup with chronic infection from 0.46 (95%CI: 0.33, 0.60) to 0.88 (95%CI: 0.68, 1.07) (P = 0.007). Conclusions In this single-center cohort, acquisition of SM in CF was associated with an acceleration in lung function decline. Among those with chronic colonization, acquisition was also associated with increased hospitalization rates.

Bacterial populations diversify during infection into distinct subpopulations that coexist within the human body. Yet, it is unknown to what extent subpopulations adapt to location-specific selective pressures as they migrate and evolve across space. Here we identify bacterial genes under local and global selection by testing for spatial co-occurrence of adaptive mutations. We sequence 552 genomes of the pathogen Stenotrophomonas maltophilia across 23 sites of the lungs from a patient with cystic fibrosis. We show that although genetically close isolates colocalize in space, distant lineages with distinct phenotypes separated by adaptive mutations spread throughout the lung, suggesting global selective pressures. Yet, for one gene (a distant homologue of the merC gene implicated in metal resistance), mutations arising independently in two lineages colocalize in space, providing evidence for location-specific selection. Our work presents a general framework for understanding how selection acts upon a pathogen that colonizes and evolves across the complex environment of the human body., The authors sequence the genomes of 552 bacterial isolates sampled across 23 sites of the lungs of a patient with cystic fibrosis, and identify bacterial genes under global and location-specific adaptation.

Burkholderia dolosa is a member of the Burkholderia cepacia complex (BCC), which is a group of bacteria that cause chronic lung infection in patients with cystic fibrosis (CF) and can be associated with outbreaks carrying high morbidity and mortality. While investigating the genomic diversity of B. dolosa strains collected from an outbreak among CF patients, we previously identified fixL as a gene showing signs of strong positive selection. This gene has homology to fixL of the rhizobial FixL/FixJ two-component system. The goals of this study were to determine the functions of FixLJ and their role in virulence in B. dolosa. We generated a fixLJ deletion mutant and complemented controls in B. dolosa strain AU0158. Using a fixK-lacZ reporter we found that FixLJ was activated in low oxygen in multiple BCC species. In a murine pneumonia model, the B. dolosa fixLJ deletion mutant was cleared faster from the lungs and spleen than wild-type B. dolosa strain AU0158 at 7 days post infection. Interestingly, the fixLJ deletion mutant made more biofilm, albeit with altered structure, but was less motile than strain AU0158. Using RNA-seq with in vitro grown bacteria, we found ~11% of the genome was differentially expressed in the fixLJ deletion mutant relative to strain AU0158. Multiple flagella-associated genes were down-regulated in the fixLJ deletion mutant, so we also evaluated virulence of a fliC deletion mutant, which lacks a flagellum. We saw no difference in the ability of the fliC deletion mutant to persist in the murine model relative to strain AU0158, suggesting factors other than flagella caused the phenotype of decreased persistence. We found the fixLJ deletion mutant to be less invasive in human lung epithelial and macrophage-like cells. In conclusion, B. dolosa fixLJ is a global regulator that controls biofilm formation, motility, intracellular invasion/persistence, and virulence., Author Summary In people with cystic fibrosis (CF), infection with bacteria in the Burkholderia cepacia complex (BCC) is often associated with clinical deterioration. In a whole-genome sequencing study of the BCC species B. dolosa, we previously identified the fixL gene of the FixL/FixJ two-component system called FixLJ to be under strong positive selective pressure during chronic infection. In this study we show that low oxygen levels activate FixLJ, and that a mutant of B. dolosa in which the fixLJ genes are deleted is less able to persist in the lungs and spread to the spleen in a lung infection model in mice. The fixLJ deletion mutant has defective motility and intracellular survival within epithelial cells and macrophage cell lines. However, a flagella mutant is fully infectious, suggesting that low motility is not responsible for the fixLJ deletion mutant’s inability to persist within the host. Analysis of global RNA expression shows that the fixLJ system regulates many genes, indicating that multiple pathways likely contribute to the low virulence of the fixLJ deletion mutant. In conclusion, B. dolosa FixLJ compose an oxygen sensor that regulates the ability of the bacteria to survive inside host cells.

Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format to assist acute care hospitals in implementing and prioritizing strategies to prevent ventilator-associated pneumonia (VAP) and other ventilator-associated events (VAEs) and to improve outcomes for mechanically ventilated adults, children, and neonates. This document updates "Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals," published in 2008. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA) and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise. The list of endorsing and supporting organizations is presented in the introduction to the 2014 updates.

Despite the recognition of Pseudomonas aeruginosa is an opportunistic pathogen, no vaccine against this bacteria have come to market. This review describes the current state-of-the-art in vaccinology for this bacterium. This includes a discussion of those at risk for infection, the types of vaccines and the approaches for empirical and targeted antigen selection under development, as well as a perspective on where the field should go. In addition, the challenges in developing a vaccine for those individuals at risk are discussed.

Burkholderia dolosa caused an outbreak in the cystic fibrosis (CF) clinic at Boston Children's Hospital from 1998 to 2005 and led to the infection of over 40 patients, many of whom died due to complications from infection by this organism. To assess whether B. dolosa significantly contributes to disease or is recognized by the host immune response, mice were infected with a sequenced outbreak B. dolosa strain, AU0158, and responses were compared to those to the well-studied CF pathogen Pseudomonas aeruginosa . In parallel, mice were also infected with a polar flagellin mutant of B. dolosa to examine the role of flagella in B. dolosa lung colonization. The results showed a higher persistence in the host by B. dolosa strains, and yet, neutrophil recruitment and cytokine production were lower than those with P. aeruginosa . The ability of host immune cells to recognize B. dolosa was then assessed, B. dolosa induced a robust cytokine response in cultured cells, and this effect was dependent on the flagella only when bacteria were dead. Together, these results suggest that B. dolosa can be recognized by host cells in vitro but may avoid or suppress the host immune response in vivo through unknown mechanisms. B. dolosa was then compared to other Burkholderia species and found to induce similar levels of cytokine production despite being internalized by macrophages more than Burkholderia cenocepacia strains. These data suggest that B. dolosa AU0158 may act differently with host cells and is recognized differently by immune systems than are other Burkholderia strains or species.

Enteral nutrition has been implicated as a risk factor for ventilator-associated pneumonia. We explored the prevalence of ventilator-associated pneumonia and its association with clinical and nutrition-related therapies in mechanically ventilated children.Prospective, multicenter, cohort study.Fifty-nine PICU in 15 countries.Children less than 18 years old, mechanically ventilated for more than 48 hours.None. Multivariable logistic regression to determine factors associated with ventilator-associated pneumonia.Data are presented as median (interquartile range) or counts (%). We enrolled 1,245 subjects (45% women; 42% surgical), age 20 months (4-84 mo), and duration of mechanical ventilation 7 days (3-13 d). Culture-positive ventilator-associated pneumonia was diagnosed in 80 patients (6.4%); duration of mechanical ventilation for this subgroup was 17 days (8-39 d). Enteral nutrition was delivered in 985 patients (79%), initiated within 48 hours in 592 patients (60%), and via postpyloric route in 354 patients (36%). Acid-suppressive agents were used in 763 patients (61%). The duration of enteral nutrition (p = 0.21), route (gastric vs postpyloric) of delivery (p = 0.94), severity of illness (p = 0.17), and diagnostic category on admission (p = 0.31) were not associated with ventilator-associated pneumonia. After adjusting for enteral nutrition days, illness severity, and site, ventilator-associated pneumonia was significantly associated with mechanical ventilation more than 10 days (odds ratio, 3.7; 95% CI, 2.2-6.5; p0.001), PICU length of stay more than 10 days (odds ratio, 1.8; 95% CI, 1.1-3.1; p = 0.029), and the use of acid-suppressive medication (odds ratio, 2.0; 95% CI, 1.2-3.6; p = 0.011).Ventilator-associated pneumonia was diagnosed in 6.5% of mechanically ventilated children in a heterogeneous multicenter cohort. We did not find a link between enteral nutrition duration or route of delivery and ventilator-associated pneumonia. In addition to duration of mechanical ventilation and length of PICU stay, the use of acid-suppressive therapy independently increased the likelihood of developing ventilator-associated pneumonia in this population. This association must be further explored in clinical trials.

To identify a pediatric ventilator-associated condition definition for use in neonates and children by exploring whether potential ventilator-associated condition definitions identify patients with worse outcomes.Retrospective cohort study and a matched cohort analysis.Pediatric, cardiac, and neonatal ICUs in five U.S. hospitals.Children 18 years old or younger ventilated for at least 1 day.None.We evaluated the evidence of worsening oxygenation via a range of thresholds for increases in daily minimum fraction of inspired oxygen (by 0.20, 0.25, and 0.30) and daily minimum mean airway pressure (by 4, 5, 6, and 7 cm H2O). We required worsening oxygenation be sustained for at least 2 days after at least 2 days of stability. We matched patients with a ventilator-associated condition to those without and used Cox proportional hazard models with frailties to examine associations with hospital mortality, hospital and ICU length of stay, and duration of ventilation. The cohort included 8,862 children with 10,209 hospitalizations and 77,751 ventilator days. For the fraction of inspired oxygen 0.25/mean airway pressure 4 definition (i.e., increase in minimum daily fraction of inspired oxygen by 0.25 or mean airway pressure by 4), rates ranged from 2.9 to 3.2 per 1,000 ventilator days depending on ICU type; the fraction of inspired oxygen 0.30/mean airway pressure 7 definition yielded ventilator-associated condition rates of 1.1-1.3 per 1,000 ventilator days. All definitions were significantly associated with greater risk of hospital death, with hazard ratios ranging from 1.6 (95% CI, 0.7-3.4) to 6.8 (2.9-16.0), depending on thresholds and ICU type. Each definition was associated with prolonged hospitalization, time in ICU, and duration of ventilation, among survivors. The advisory board of the study proposed using the fraction of inspired oxygen 0.25/mean airway pressure 4 thresholds to identify pediatric ventilator-associated conditions in ICUs.Pediatric patients with ventilator-associated conditions are at substantially higher risk for mortality and morbidity across ICUs, regardless of thresholds used. Next steps include identification of risk factors, etiologies, and preventative measures for pediatric ventilator-associated conditions.

Bacterial pathogens evolve during the infection of their human host(1-8), but separating adaptive and neutral mutations remains challenging(9-11). Here we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple individuals. We conducted a retrospective study of a Burkholderia dolosa outbreak among subjects with cystic fibrosis, sequencing the genomes of 112 isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired nonsynonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes affect important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition and implicate oxygen-dependent regulation as paramount in lung infections. Several genes have not previously been implicated in pathogenesis and may represent new therapeutic targets. The identification of parallel molecular evolution as a pathogen spreads among multiple individuals points to the key selection forces it experiences within human hosts.

Burkholderia dolosa caused an outbreak in the cystic fibrosis clinic at Boston Children's Hospital and was associated with high mortality in these patients. This species is part of a larger complex of opportunistic pathogens known as the Burkholderia cepacia complex (Bcc). Compared to other species in the Bcc, B. dolosa is highly transmissible; thus understanding its virulence mechanisms is important for preventing future outbreaks. The genome of one of the outbreak strains, AU0158, revealed a homolog of the lafA gene encoding a putative lateral flagellin, which, in other non-Bcc species, is used for movement on solid surfaces, attachment to host cells, or movement inside host cells. Here, we analyzed the conservation of the lafA gene and protein sequences, which are distinct from those of the polar flagella, and found lafA homologs to be present in numerous β-proteobacteria but notably absent from most other Bcc species. A lafA deletion mutant in B. dolosa showed a greater swimming motility than wild-type due to an increase in the number of polar flagella, but did not appear to contribute to biofilm formation, host cell invasion, or murine lung colonization or persistence over time. However, the lafA gene was important for cytokine production in human peripheral blood mononuclear cells, suggesting it may have a role in recognition by the human immune response.

Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22 + TCRβ + cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection.

BACKGROUNDAs mandatory public reporting of healthcare-associated infections increases, there is concern that clinicians could attempt to decrease rates by avoiding the diagnosis of reportable infections.OBJECTIVETo determine whether blood culture and antibiotic utilization changed after mandatory public reporting of central line–associated bloodstream infection (CLABSI).DESIGNInterrupted time-series of blood culture and antibiotic rates before and after state-specific implementation of mandatory public reporting. We analyzed data from pediatric and neonatal intensive care units (ICUs) at 17 children’s hospitals that contributed to the Pediatric Health Information System administrative database. We used multivariable regression with generalized linear mixed-effects models to determine adjusted rate ratios (ARRs) after implementation of mandatory public reporting. We conducted subgroup analysis on patients with central venous catheters. To assess temporal trends, we separately analyzed data from 4 pediatric hospitals in states without mandatory public reporting.RESULTSThere was no significant effect of mandatory public reporting on rates of blood culture (pediatric ICU ARR, 1.03 [95% CI, 0.82–1.28]; neonatal ICU ARR, 1.06 [0.85–1.33]) or antibiotic utilization (pediatric ICU ARR, 0.86 [0.72–1.04]; neonatal ICU ARR, 1.09 [0.87–1.35]). Results were similar in the subgroup of patients with central venous catheter codes. Hospitals with and without mandatory public reporting experienced small decreases in blood culture and antibiotic use across the study period.CONCLUSIONSMandatory public reporting of central line–associated bloodstream infection did not impact blood culture and antibiotic utilization, suggesting that clinicians have not shifted their practice in an attempt to detect fewer infections.Infect Control Hosp Epidemiol 2015;36(8):878–885

Pseudomonas aeruginosa can cause sight-threatening corneal infections in humans, particularly those who wear contact lenses. We have previously shown that a live-attenuated P. aeruginosa vaccine given intranasally protected mice against acute lethal pneumonia in a lipopolysaccharide (LPS) serogroup-specific manner. In the current study, we evaluated the protective and therapeutic efficacies, as well as the target antigens, of this vaccine in a murine corneal infection model. C3H/HeN mice were nasally immunized with the vaccine (an aroA deletion mutant of strain PAO1, designated PAO1Δ aroA ) or with Escherichia coli as a control and were challenged 3 weeks later by inoculating the scratch-injured cornea with P. aeruginosa . For passive prophylaxis and therapy, we utilized a serum raised in rabbits nasally immunized with PAO1Δ aroA or E. coli . Outcome measures included corneal pathology scores and, in some experiments, reductions in total and internalized bacterial CFU. We found that both active and passive immunization reduced corneal pathology scores after challenge with a variety of P. aeruginosa strains, including several serogroup-heterologous strains. Even when given therapeutically starting as late as 24 h after infection, the rabbit antiserum to PAO1Δ aroA was effective at reducing corneal pathology scores. Immunotherapy of established infections also reduced the numbers of total and internalized corneal P. aeruginosa bacteria. Experiments using absorbed sera showed that the protective antibodies are specific to outer membrane proteins. Thus, live-attenuated P. aeruginosa vaccines delivered nasally protect against corneal infections in mice and potentially can be used to prepare passive therapy reagents for the treatment of established P. aeruginosa corneal infections caused by diverse LPS serogroups.

Two fully human mAbs specific for epitopes dependent on intact carboxylate groups on the C6 carbon of the mannuronic acid components of Pseudomonas aeruginosa alginate were found to promote phagocytic killing of both mucoid and nonmucoid strains as well as protection against both types of strains in a mouse model of acute pneumonia. The specificity of the mAbs for alginate was determined by ELISA and killing assays. Some strains of P. aeruginosa did not make detectable alginate in vitro, but in vivo protection against lethal pneumonia was obtained and shown to be due to rapid induction of expression of alginate in the murine lung. No protection against strains genetically unable to make alginate was achieved. These mAbs have potential to be passive therapeutic reagents for all strains of P. aeruginosa and the results document that alginate is a target for the proper type of protective Ab even when expressed at low levels on phenotypically nonmucoid strains.

As an immune-privileged site, the eye, and particularly the outer corneal surface, lacks resident mature immune effector cells. Physical barriers and innate mediators are the best-described effectors of immunity in the cornea. When the barriers are breached, infection can result in rapid tissue destruction, leading to loss of visual acuity and frank blindness. To determine the cellular and molecular components needed for effective adaptive immunity on the corneal surface, we investigated which immune system effectors were required for protection against Staphylococcus aureus corneal infections in mice, which are a serious cause of human eye infections. Both systemically injected and topically applied antibodies to the conserved cell surface polysaccharide poly- N -acetylglucosamine (PNAG) were effective at mediating reductions in corneal pathology and bacterial levels. Additional host factors impacting protection included intercellular adhesion molecule 1 (ICAM-1)-dependent polymorphonuclear leukocyte (PMN) recruitment, functional CD4 + T cells, signaling via the interleukin-17 (IL-17) receptor, and IL-22 production. In germfree mice, there was no protective efficacy of antibody to PNAG due to the lack of LY6G + inflammatory cell coeffector recruitment to the cornea. Protection was manifest after 3 weeks of exposure to conventional mice and acquisition of a resident microbiota. We conclude that in the anterior eye, ICAM-1-mediated PMN recruitment to the infected cornea along with endogenous microbiota-matured CD4 + T cells producing both IL-17 and IL-22 is required for antibody to PNAG to protect against S. aureus infection.

Pseudomonas aeruginosa is the nosocomial bacterial pathogen most commonly isolated from the respiratory tract. Animal models of this infection are extremely valuable for studies of virulence and immunity. We thus evaluated the utility of a simple model of acute pneumonia for analyzing P. aeruginosa virulence by characterizing the course of bacterial infection in BALB/c mice following application of bacteria to the nares of anesthetized animals. Bacterial aspiration into the lungs was rapid, and 67 to 100% of the inoculum could be recovered within minutes from the lungs, with 0.1 to 1% of the inoculum found intracellularly shortly after infection. At later time points up to 10% of the bacteria were intracellular, as revealed by gentamicin exclusion assays on single-cell suspensions of infected lungs. Expression of exoenzyme U (ExoU) by P. aeruginosa is associated with a cytotoxic effect on epithelial cells in vitro and virulence in animal models. Insertional mutations in the exoU gene confer a noncytotoxic phenotype on mutant strains and decrease virulence for animals. We used the model of acute pneumonia to determine whether introduction of the exoU gene into noncytotoxic strains of P. aeruginosa lacking this gene affected virulence. Seven phenotypically noncytotoxic P. aeruginosa strains were transformed with pUCP19 exoUspcU which carries the exoU gene and its associated chaperone. Three of these strains became cytotoxic to cultured epithelial cells in vitro. These strains all secreted ExoU, as confirmed by detection of the ExoU protein with specific antisera. The 50% lethal dose of exoU -expressing strains was significantly lower for all three P. aeruginosa isolates carrying plasmid pUCP19 exoUspcU than for the isogenic exoU -negative strains. mRNA specific for ExoU was readily detected in the lungs of animals infected with the transformed P. aeruginosa strains. Introduction of the exoU gene confers a cytotoxic phenotype on some, but not all, otherwise-noncytotoxic P. aeruginosa strains and, for recombinant strains that could express ExoU, there was markedly increased virulence in a murine model of acute pneumonia and systemic spread.

Advances in sequencing technologies have enabled the identification of mutations acquired by bacterial pathogens during infection. However, it remains unclear whether adaptive mutations fix in the population or lead to pathogen diversification within the patient. Here we study the genotypic diversity of Burkholderia dolosa within individuals with cystic fibrosis by resequencing individual colonies and whole populations from single sputum samples. We find extensive intrasample diversity, suggesting that mutations rarely fix in a patient's pathogen population--instead, diversifying lineages coexist for many years. Under strong selection, multiple adaptive mutations arise, but none of these sweep to fixation, generating lasting allele diversity that provides a recorded signature of past selection. Genes involved in outer-membrane components, iron scavenging and antibiotic resistance all showed this signature of within-patient selection. These results offer a general and rapid approach for identifying the selective pressures acting on a pathogen in individual patients based on single clinical samples.

A feature shared by many inflammatory lung diseases is excessive neutrophilic infiltration. Neutrophil homing to airspaces involve multiple factors produced by several distinct cell types. Hepoxilin A3 is a neutrophil chemoattractant produced by pathogen-infected epithelial cells that is hypothesized to facilitate neutrophil breach of mucosal barriers. Using a Transwell model of lung epithelial barriers infected with Pseudomonas aeruginosa, we explored the role of hepoxilin A3 in neutrophil transepithelial migration. Pharmacological inhibitors of the enzymatic pathways necessary to generate hepoxilin A3, including phospholipase A2 and 12-lipoxygenase, potently interfere with P. aeruginosa-induced neutrophil transepithelial migration. Both transformed and primary human lung epithelial cells infected with P. aeruginosa generate hepoxilin A3 precursor arachidonic acid. All four known lipoxygenase enzymes capable of synthesizing hepoxilin A3 are expressed in lung epithelial cell lines, primary small airway epithelial cells, and human bronchial epithelial cells. Lung epithelial cells produce increased hepoxilin A3 and lipid-derived neutrophil chemotactic activity in response to P. aeruginosa infection. Lipid-derived chemotactic activity is soluble epoxide hydrolase sensitive, consistent with hepoxilin A3 serving a chemotactic role. Stable inhibitory structural analogs of hepoxilin A3 are capable of impeding P. aeruginosa-induced neutrophil transepithelial migration. Finally, intranasal infection of mice with P. aeruginosa promotes enhanced cellular infiltrate into the airspace, as well as increased concentration of the 12-lipoxygenase metabolites hepoxilin A3 and 12-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid. Data generated from multiple models in this study provide further evidence that hepoxilin A3 is produced in response to lung pathogenic bacteria and functions to drive neutrophils across epithelial barriers.

HFOV is a mode of ventilation that can achieve oxygenation and ventilation while maintaining maximal lung recruitment on the deflation limb of its pressure-volume curve. The primary theoretical advantages of HFOV over CMV in the management of acute lung injury are that HFOV allows adequate alveolar ventilation with minimal peak-trough pressure changes, provides lung recruitment, and avoids end-inspiratory overdistension of the relatively compliant nondependent lung. Taken together, the results of studies in animals, preterm and term neonates, and older pediatric patients reveal that an "open-lung" strategy, with the goal of a high end-expiratory lung volume, is safe and superior to CMV in both the short-term (rapidly improved oxygenation and/or ventilation) and longer-term (lower incidence of chronic lung disease). The improved longer-term clinical outcomes on HFOV are presumably because of less ventilator-induced lung injury. As experience with HFOV in older patients grows, ventilator technology matures, and understanding of the pathophysiology of acute respiratory distress syndrome (RDS) deepens, it is likely that HFOV will find widespread use for the management of respiratory failure caused by acute lung injury in patients from preterm neonates to adults.

PCR has proved superior to conventional blood culture for diagnosing bacteraemia in the presence of antibiotics. Nevertheless, even PCR might yield false-negative results if the template DNA were to be cleaved by serum DNAases after antibiotics had induced bacterial death. To evaluate the cleavage of bacterial template DNA by human serum DNAase I, serum samples inoculated with purified Escherichia coli DNA were incubated with increasing amounts of recombinant human DNAase (rhDNAase) and then examined by a PCR specific for E. coli. As a prerequisite of potential DNAase attack, the release of E. coli DNA after antibiotic-induced bacterial death was quantified by fluorescence microscopy and flow cytometry. Finally, the influence of rhDNAase on the PCR-based detection of antibiotic-killed E. coli in serum was assessed. The results indicated that purified E. coli DNA is remarkably stable in human serum; positive PCR results did not decrease significantly until the ratio of recombinant human DNAase I:E. coli rose to 106:1. As only 14.8-28.4% of the total E. coli DNA was released after antibiotic killing, the PCR-based detection of E. coli fell by only 10% when cefotaxime-killed E. coli were incubated with rhDNAase. It was concluded that human serum DNAases and antibiotic killing do not compromise the reliability of PCR examinations for bacteraemia.

PURPOSE: To report a case of Klebsiella subretinal abscess with a successful visual outcome with treatment and to review the literature pertaining to focal intraocular infection in bacterial endophthalmitis. METHODS: Clinical data including medical history, findings on physical examination, blood cultures, and an abdominal computed tomographic scan were collected in a 32-year-old man with Klebsiella sepsis, liver abscesses, and a focal subretinal abscess. Ocular data including visual acuity, fundus photographs, fluorescein angiography, and ultrasound were evaluated, as were results of culture and histopathologic studies. RESULTS: Despite immediate intervention, including vitreous tap and intravitreal antibiotics, the eye deteriorated, with enlargement of the abscess. A pars plana vitrectomy was performed in which the subretinal abscess material was removed after an extensive retinectomy of the involved area in association with an endophotocoagulative barrier and intravitreal amikacin without gas or oil tamponade. Culture confirmed Klebsiella subretinal infection. A retinal detachment occurred 1 month postoperatively and was successfully repaired. Visual acuity was 20/30 and has remained stable for 14 months. CONCLUSION: Klebsiella endophthalmitis with subretinal abscess formation is a rare but devastating ocular condition. In the present case, prompt intervention with extensive retinectomy, complete abscess excision, and intravitreal antibiotic therapy resulted in unprecedented visual recovery.