The association of penicillin allergy with outcomes after open ventral hernia repair.

BACKGROUND: Up to 11% of patients report a penicillin allergy (PA), with 1-2% demonstrating a true IgE mediated allergy upon testing. PA patients often receive non-beta-lactam antibiotic surgical prophylaxis (non-BLP). This study evaluates the relationship of PA to outcomes after open ventral hernia repair (OVHR). METHODS: A prospective institutional database was queried for patients undergoing OVHR. Demographics, operative characteristics, and outcomes were evaluated by the reported PA and the administration of beta-lactam prophylaxis (BLP). RESULTS: Allergy histories were reviewed in 1178 patients. PA was reported in 21.6% of patients, with 55.5% reporting rash or hives, 15.0% airway compromise or anaphylaxis, and 29.5% no specific reaction. BLP was administered to 76.3% of patients, including 22.1% of PA patients and 89.9% of patients without PA. PA patients were more often female (64.6% PA patients vs. 56% non-PA, p = 0.01), with higher rates of chronic steroids, MRSA, anxiety, asthma, COPD, chronic pain, and sleep apnea (p < 0.03 all values). PA patients had higher rates of contaminated cases, including mesh infection and fistula. Of the 683 clean cases, 82.1% received BLP. Of the 117 clean contaminated cases (CDC wound class 2), 82.9% received BLP, which was associated with reduced long-term readmission for hernia complications (21.5 vs. 55%, p = 0.002, OR 0.27, CI 0.09-0.83). In the 120 CDC wound class 3 and 4 patients, 65.8% received BLP. In multivariate analysis, BLP was associated with lower rates of reoperation (OR 0.31, CI 0.12-0.76) and recurrence (OR 0.32, CI 0.11-0.86). BLP was given to 22.1% of the PA patients with no adverse reactions noted. CONCLUSION: PA patients had more comorbidities and complex ventral hernias. When controlling for contamination and MRSA history, BLP is associated with improved outcomes particularly in contaminated cases. PA may be a risk factor for patient complexity, and further studies are warranted to determine if allergy testing can be warranted in known or anticipated contaminated cases.

The cutaneous microbiome in outpatients presenting with acute skin abscesses.

BACKGROUND: Previous studies have demonstrated an association between antibiotic use and the development of skin abscesses. We tested the hypothesis that alterations in the composition of the cutaneous microbiota may predispose individuals to skin abscesses. METHODS: We studied 25 patients with skin abscesses and 25 age-matched controls, who each completed a questionnaire. Skin swab samples were obtained for DNA analysis from 4 sites around the abscess site (hereafter, "peri-abscess specimens") and from similar sites on the patient's contralateral side and on healthy control subjects. DNA was extracted and analyzed by quantitative polymerase chain reaction (qPCR) and high-throughput sequencing. The purulent abscess drainage was sent for culture. RESULTS: Fifteen patients with abscess were infected with Staphylococcus aureus. Use of nuc qPCR to quantitate S. aureus revealed a significantly greater frequency of positive results for peri-abscess and contralateral skin samples, compared with control skin specimens. Analysis of community structure showed greater heterogeneity in the control samples than in the peri-abscess and contralateral samples. Metagenomic analysis detected significantly more predicted genes related to metabolic activity in the peri-abscess specimens than in the control samples. CONCLUSIONS: The peri-abscess microbiome was similar to the contralateral microbiome, but both microbiomes differed from that for control patients. Host characteristics affecting microbial populations might be important determinants of abscess risk.

Comparison of culture and molecular techniques for microbial community characterization in infected necrotizing pancreatitis.

BACKGROUND: Infected necrotizing pancreatitis is associated with significant morbidity and mortality. Peripancreatic fluid cultures may fail to identify all the infecting organisms. The aim of this study was to compare the bacterial biome of peripancreatic fluid from infected necrotizing pancreatitis patients using 16S ribosomal RNA (rRNA) DNA deep sequencing and quantitative polymerase chain reaction (qPCR) targeting the 16S rRNA gene versus standard laboratory culture. MATERIALS AND METHODS: Peripancreatic fluid was collected during operative or radiologic intervention and samples sent for culture. In parallel, microbial DNA was extracted, qPCR targeting the 16S rRNA gene and 16S rRNA PCR amplification followed by Illumina deep sequencing were performed. RESULTS: Using culture techniques, the bacterial strains most frequently identified were gram-negative rods (Escherichia coli, Klebsiella pneumoniae) and Enterococcus. Samples in which culture results were negative had copy numbers of the 16S rRNA gene close to background in qPCR analysis. For samples with high bacterial load, sequencing results were in some cases in good agreement with culture data, whereas in others there were disagreements, likely due to differences in taxonomic classification, cultivability, and differing susceptibility to background contamination. Sequencing results appeared generally unreliable in cases of negative culture where little microbial DNA was input into qPCR sequencing reactions. CONCLUSIONS: Both sequencing and culture data display their own sources of bias and potential error. Consideration of data from multiple techniques will yield a more accurate view of bacterial infections than can be achieved by any single technique.

Cutaneous Microbiome Profiles Following Chlorhexidine Treatment in a 72-Hour Daily Follow-Up Paired Design: a Pilot Study.

Venous catheter-related bloodstream infections represent a significant problem in the United States. Our objective was to determine daily changes in skin microbiome profiles up to 72h postchlorhexidine treatment. Left and right forearm skin swab samples were obtained from 10 healthy volunteers over 72h at 24h intervals. Dorsal surface of left arm was treated with chlorohexidine gluconate (CHG) at initial time point (T = 0), while the right arm remained untreated (control). Swab samples were obtained shortly before (T = 0) and after CHG treatment (T = 24-48-72h). Bacterial DNA extraction, 16S rRNA gene V1-V3 sequencing and taxonomic annotation were performed using ZymoBIOMICS pipeline. PERMANOVA, linear discriminant and bacterial interaction network analyses were performed. A total of 13 total phyla, 273 genera, and 950 total species were detected across all time points, CHG-treated or CHG-untreated. Most abundant species included Cutibacterium acnes, Staphylococcus epidermidis, and Rothia Mucilaginosa. Low biomass-related inconsistent taxa detection was observed. PERMANOVA suggested a marginal difference between CHG-treated and CHG-untreated microbiome profiles (Genera: P(perm) = 0.0531; Species: P(perm) = 0.0450). Bacterial interaction network guided PERMANOVA analyses detected a microbiome change over time, suggesting a consistent CHG treatment-specific change. LEfSe identified Finegoldia magna, Bacillus pumilus, Bacillus thermoamylovorans as the only distinctive species. These species were more abundant and/or present post-CHG treatment in the CHG-treated group. These findings suggest that the skin microbiome was not significantly different 24, 48, or 72h after CHG treatment. Previous culture-based studies have found similar results after 24h. Future studies will be needed to determine the mechanisms of bacterial regrowth after CHG treatment. IMPORTANCE Annually, over 80,000 central line infections occur in the United States. Understanding the pathogenesis of these infections is crucial. Chlorhexidine is the most commonly used skin preparation before line placement. We hypothesized that the use of chlorhexidine and dressings will alter the normal arm skin microbiome over a period of 72h. We used 16S-rRNA gene next generation sequencing (NGS) to determine the forearm skin microbiome of volunteers. The left arm was swabbed with chlorhexidine and the right arm served as control. The skin microbiome returned to normal after 24h. Our NGS results confirm findings of two previous culture-based studies. Relative abundance of Bacillus spp. in the chlorhexidine-treated samples was increased, consistent with one previous study. Based on the results of this pilot study, we will need to measure viable bacteria during a 24h time course following chlorhexidine treatment to understand the source of skin microbiome replenishment.

Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol.

OBJECTIVE: We sought to determine the association between time to initial antibiotics and mortality of patients with septic shock treated with an emergency department-based early resuscitation protocol. DESIGN: Preplanned analysis of a multicenter randomized controlled trial of early sepsis resuscitation. SETTING: Three urban U.S. emergency departments. PATIENTS: Adult patients with septic shock. INTERVENTIONS: A quantitative resuscitation protocol in the emergency department targeting three physiological variables: central venous pressure, mean arterial pressure, and either central venous oxygen saturation or lactate clearance. The study protocol was continued until all end points were achieved or a maximum of 6 hrs. MEASUREMENTS AND MAIN RESULTS: Data on patients who received an initial dose of antibiotics after presentation to the emergency department were categorized based on both time from triage and time from shock recognition to initiation of antibiotics. The primary outcome was inhospital mortality. Of 291 included patients, mortality did not change with hourly delays in antibiotic administration up to 6 hrs after triage: 1 hr (odds ratio [OR], 1.2; 0.6-2.5), 2 hrs (OR, 0.71; 0.4-1.3), 3 hrs (OR, 0.59; 0.3-1.3). Mortality was significantly increased in patients who received initial antibiotics after shock recognition (n = 172 [59%]) compared with before shock recognition (OR, 2.4; 1.1-4.5); however, among patients who received antibiotics after shock recognition, mortality did not change with hourly delays in antibiotic administration. CONCLUSION: In this large, prospective study of emergency department patients with septic shock, we found no increase in mortality with each hour delay to administration of antibiotics after triage. However, delay in antibiotics until after shock recognition was associated with increased mortality.

Etiology of illness in patients with severe sepsis admitted to the hospital from the emergency department.

BACKGROUND: Patients identified with sepsis in the emergency department often are treated on the basis of the presumption of infection; however, various noninfectious conditions that require specific treatments have clinical presentations very similar to that of sepsis. Our aim was to describe the etiology of illness in patients identified and treated for severe sepsis in the emergency department. METHODS: We conducted a prospective observational study of patients treated with goal-directed resuscitation for severe sepsis in the emergency department. Inclusion criteria were suspected infection, 2 or more criteria for systemic inflammation, and evidence of hypoperfusion. Exclusion criteria were age of <18 years and the need for immediate surgery. Clinical data on eligible patients were prospectively collected for 2 years. Blinded observers used a priori definitions to determine the final cause of hospitalization. RESULTS: In total, 211 patients were enrolled; 95 (45%) had positive culture results, and 116 (55%) had negative culture results. The overall mortality rate was 19%. Patients with positive culture results were more likely to have indwelling vascular lines (P = .03), be residents of nursing homes (P = .04), and have a shorter time to administration of antibiotics in the emergency department (83 vs 97 min; P = .03). Of patients with negative culture results, 44% had clinical infections, 8% had atypical infections, 32% had noninfectious mimics, and 16% had an illness of indeterminate etiology. CONCLUSION: In this study, we found that >50% of patients identified and treated for severe sepsis in the emergency department had negative culture results. Of patients identified with a sepsis syndrome at presentation, 18% had a noninfectious diagnosis that mimicked sepsis, and the clinical characteristics of these patients were similar to those of patients with culture-positive sepsis.

Prospective external validation of the clinical effectiveness of an emergency department-based early goal-directed therapy protocol for severe sepsis and septic shock.

OBJECTIVE: To determine the clinical effectiveness of implementing early goal-directed therapy (EGDT) as a routine protocol in the emergency department (ED). METHODS: Prospective interventional study conducted over 2 years at an urban ED. Inclusion criteria included suspected infection, criteria for systemic inflammation, and either systolic BP < 90 mm Hg after a fluid bolus or lactate concentration >/= 4 mol/L. Exclusion criteria were age < 18 years, contraindication to a chest central venous catheter, and need for immediate surgery. We prospectively recorded preintervention clinical and mortality data on consecutive, eligible patients for 1 year when treatment was at the discretion of board-certified emergency physicians. We then implemented an EGDT protocol (the intervention) and recorded clinical data and mortality rates for 1 year. Prior to the first year, we defined a 33% relative reduction in mortality (relative mortality reduction that was found in the original EGDT trial) to indicate clinical effectiveness of the intervention. RESULTS: We enrolled 79 patients in the preintervention year and 77 patients in the postintervention year. Compared with the preintervention year, patients in the postintervention year received significantly greater crystalloid volume (2.54 L vs 4.66 L, p < 0.001) and frequency of vasopressor infusion (34% vs 69%, p < 0.001) during the initial resuscitation. In-hospital mortality was 21 of 79 patients (27%) before intervention, compared with 14 of 77 patients (18%) after intervention (absolute difference, - 9%; 95% confidence interval, + 5 to - 21%). CONCLUSIONS: Implementation of EGDT in our ED was associated with a 9% absolute (33% relative) mortality reduction. Our data provide external validation of the clinical effectiveness of EGDT to treat sepsis and septic shock in the ED.