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The article presents the discussion on length of antimicrobial therapy for ventilator associated pneumonia (VAP). Topics include creating a metaanalysis on risk of recurrent pneumonia with short- versus long-course therapy for the 2016 guidelines; and fluctuation in cough, sputum, dyspnea, and laboratory results prompting repeat culturing, imaging, and increase misdiagnosis .

Background: Previous meta-analyses suggested that treating hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), with empiric carbapenems was associated with lower mortality rates but higher rates of clinical failure for pseudomonal pneumonia. This study was an updated meta-analysis with sensitivity analyses and meta-regression to better understand the impact of carbapenem use in HAP/VAP.Research Question: What is the efficacy of carbapenems for empiric treatment of nosocomial pneumonia?Study Design and Methods: Databases were searched for randomized controlled studies evaluating empiric treatment for HAP and/or VAP, and studies were included comparing carbapenem- vs non-carbapenem-containing regimens. The primary outcome was all-cause mortality. Secondary outcomes included subgroup stratification and resistance development.Results: Of 9,140 references, 20 trials enrolling 5,489 patients met inclusion criteria. For mortality, carbapenem use had a risk ratio (RR) of 0.84 (95% CI, 0.74-0.96; P = .01). Stratified according to VAP proportion (< 33%, 33%-66%, and > 66%), RRs were 0.95 (95% CI, 0.77-1.17; P = .66), 0.78 (95% CI, 0.57-1.07; P = .13), and 0.81 (95% CI, 0.65-0.99; P = .04), respectively. Stratified according to severity, only groups with Acute Physiology and Chronic Health Evaluation II scores < 14 and between 14 and 17 showed mortality benefit (RRs of 0.64 [95% CI, 0.45-0.92; P = .01] and 0.77 [95% CI, 0.61-0.97; P = .03]). Meta-regression did not show an association between Pseudomonas prevalence and mortality (P = .44). Carbapenem use showed a trend toward developing resistance (RR, 1.40; 95% CI, 0.95-2.06; P = .09) and a 96% probability of resistance emergence.Interpretation: Carbapenem-based empiric regimens were associated with lower mortality rates compared with non-carbapenems, largely driven by trials of VAP. The mortality effect was not observed in trials with high disease severity and was not associated with Pseudomonas. The mortality difference was observed mainly in studies that used ceftazidime as control. There was a trend toward increasing resistance associated with carbapenems.Trial Registry: International Prospective Register of Systematic Reviews; No. CRD42018093602; URL: https://www.crd.york.ac.uk/prospero/. [ABSTRACT FROM AUTHOR]

The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics. [ABSTRACT FROM AUTHOR]

Purpose: Prognosis of solid organ transplant (SOT) recipients has improved, mainly because of better prevention of rejection by immunosuppressive therapies. However, SOT recipients are highly susceptible to conventional and opportunistic infections, which represent a major cause of morbidity, graft dysfunction and mortality.Methods: Narrative review.Results: We cover the current epidemiology and main aspects of infections in SOT recipients including risk factors such as postoperative risks and specific risks for different transplant recipients, key points on anti-infective prophylaxis as well as diagnostic and therapeutic approaches. We provide an up-to-date guide for management of the main syndromes that can be encountered in SOT recipients including acute respiratory failure, sepsis or septic shock, and central nervous system infections as well as bacterial infections with multidrug-resistant strains, invasive fungal diseases, viral infections and less common pathogens that may impact this patient population.Conclusion: We provide state-of the art review of available knowledge of critically ill SOT patients with infections. [ABSTRACT FROM AUTHOR]

And this is yet an incompletely solved question because we need to know precisely the right duration of antibiotic therapy necessary to cure each specific infection in individual patients. Consequently, the recommendations for the duration of antibiotic therapy began to change and nowadays, for the majority of acute bacterial infections in critically ill patients, including hospital-acquired pneumonias, is approximately 7 days ([8]). The authors selected RCTs by three different strategies to minimize duration of antibiotic therapy in critically ill patients: procalcitonin-guided algorithm, clinical algorithm, and fixed antibiotic duration. [Extracted from the article]

The article discusses the efficacy of antibiotic combination therapy for patients with gram-negative septic shock. It mentions that gram-negative septic shock is one of the most common life-threatening infections worldwide. It presents a comparison of the efficacy of antibiotic combination therapy and monotherapy for patient with gram-negative septic shock.

Background: Both typical and atypical bacteria can cause community-acquired pneumonia (CAP); however, the need for empiric atypical coverage remains controversial. Our objective was to evaluate the impact of antibiotic regimens with atypical coverage (a fluoroquinolone or combination of a macrolide/doxycycline with a β-lactam) to a regimen without atypical antibiotic coverage (β-lactam monotherapy) on rates of clinical failure (primary endpoint), mortality, bacteriologic failure, and adverse events, (secondary endpoints).Methods: We searched the PubMed, EMBASE and Cochrane Library databases for relevant RCTs of hospitalized CAP adults. We estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a fixed-effect model, but used a random-effects model if significant heterogeneity (I 2 ) was observed.Results: Five RCTs with a total of 2011 patients were retained. A statistically significant lower clinical failure rate was observed with empiric atypical coverage (RR, 0.851 [95% CI, 0.732-0.99; P = 0.037]; I 2  = 0%). The secondary outcomes did not differ between the two study groups: mortality (RR = 0.549 [95% CI, 0.259-1.165, P = 0.118], I 2  = 61.434%) bacteriologic failure (RR = 0.816 [95% CI, 0.523-1.272, P = 0.369], I 2  = 0%), diarrhea (RR = 0.746 [95% CI, 0.311-1.790, P = 0.512], I 2  = 65.048%), and adverse events requiring antibiotic discontinuation (RR = 0.83 [95% CI, 0.542-1.270, P = 0.39], I 2  = 0%).Conclusions: Empiric atypical coverage was associated with a significant reduction in clinical failure in hospitalized adults with CAP. Reduction in mortality, bacterial failure, diarrhea, and discontinuation due to adverse effects were not significantly different between groups, but all estimates favored atypical coverage. Our findings provide support for the current guidelines recommendations to include empiric atypical coverage. [ABSTRACT FROM AUTHOR]

The article discusses a research study which tested the hypothesis that linezolid may be superior to glycopeptides such as vancomycin or teicoplanin for treatment of nonsocial pneumonia. Findings showed the clinical cure relative risk and microbiological eradication relative risk of linezolid versus glycopeptides. Analysis of methicillin-resistant Staphylococcus aureus subgroup also yielded a microbiological eradication relative risk. Results revealed the higher risks of thrombocytopenia and gastrointestinal events with linezolid.

Keywords: septic shock; Staphylococcus aureus; timing of antibiotics EN septic shock Staphylococcus aureus timing of antibiotics 608 609 2 04/20/20 20200401 NES 200401 John Wooden, former coach of the UCLA Bruins basketball team, was famous for encouraging his cagers to "be quick, but don't hurry". Utilizing a U.S. Veterans Affairs database, the authors identified 506 patients from 122 hospitals (between 2003 and 2015) with septic shock and I S. aureus i bacteremia and measured the time to appropriate antibiotics from the moment the patient was triaged in the emergency department (ED). [Extracted from the article]

Cefepime hydrochloride is approved for pneumonia, empirical therapy for febrile neutropenia, uncomplicated and complicated urinary tract infections, uncomplicated skin and skin structure infections and complicated intra-abdominal infections. A recent meta-analysis by Yahav et al. (Lancet Infect Dis 2007; 7: 338–48) concluded that cefepime was associated with a statistically significant increase in mortality (risk ratio 1.26, 95% confidence interval 1.08–1.49) when compared with other antibiotics. The US FDA decided to re-evaluate the meta-analysis data in collaboration with the drug sponsor. Two years later the FDA Alert summarized that ‘data do not indicate a higher rate of death in cefepime-treated patients. Cefepime remains an appropriate therapy for its approved indications.’ However, a thorough evaluation of the 52-page FDA report still shows that safety remains an unresolved issue. A Bayesian re-appraisal of the findings by the FDA and by Yahav et al. indicates that there is a 90.9% (by FDA trial-level meta-analysis), 80.8% (by FDA patient-level meta-analysis) and 99.2% (by Yahav et al. meta-analysis) probability that cefepime raises mortality in neutropenic fever patients, which translates into the following numbers needed to harm (NNH), i.e. to cause one extra death with the use of cefepime: FDA trial-level meta-analysis, NNH = 109; FDA patient-level meta-analysis, NNH = 76; Yahav et al. meta-analysis, NNH = 54. A similar harmful probability was observed with skin structure infections but not with pneumonias, intra-abdominal infections and urinary tract infections. In conclusion, cefepime should be avoided in patients with neutropenic fever or with skin structure infections. [ABSTRACT FROM PUBLISHER]

The article discusses the beneficial outcomes of procalcitonin-guided treatments in critically ill patients with sepsis. The author agrees that fast initiation of appropriate antibiotics is the most effective treatment intervention to prevent mortality in critically ill patients with sepsis. The author believes that unnecessary prolonged use of antibiotics can have harmful effects, such as serious drug side effects, development of Clostridium difficile colitis, and antibiotic resistance.

Background Patients hospitalized with sepsis are commonly treated with antibiotics for 10–21 days. Evidence is lacking to support this duration. We hypothesize that the sequential measurement of procalcitonin [PCT] (host biomarker) and endotoxin activity assay [EAA] (microorganism biomarker) could provide evidence to safely reduce antibiotic exposure. Methods Consented patients with bacteremic sepsis on antibiotics for <48 hours had PCT and EAA measured every other day until discharge or 14 days. Investigators and care providers were blinded to results. Median (interquartile), days to biomarker clearance (reduction from baseline PCT> 80% and EAA> 0.1), and univariate/multivariate regression done for all analyses. Clinical response was evaluated by blinded investigators. Results We enrolled 215 patients. Median age: 60 years old (18); Female 45%; Baseline: Temperature: 38.5°C (0.7); WBC: 11.4 (7.7), SIRS: 3 (1); APACHE II: 19.2 (8); 60% had severe sepsis (61% Gram-negative; 39% Gram-positive). Sepsis source: 33% abdominal, 22% line, 19% urinary, 12% cutaneous; 8% pulmonary; 6% other. Findings: Day 0: PCT 4.62 (19), EAA 0.53 (0.24); Days to Clearance: PCT: 4.0 (4), EAA: 4.0 (4), and PCT/EAA: 4.0 (4). At the day of biomarker clearance patients also demonstrated clinical response. The median duration of antibiotics was 16 days [7 inpatient plus 9 outpatient-days]. Compared with both total and in-hospital antibiotic duration, time to clearance was significantly shorter: PCT (P < 0.0001), EAA (P < 0.0001), PCT/EAA (P < 0.0001). After multivariate adjustment for disease severity with APACHE II and organ failure, time-to-clearance for each or both biomarkers remained significantly shorter by 12 and 3 days compared with total and in-hospital antibiotic days, respectively. Additionally, a faster time to PCT/EAA clearance was associated with a 75% mortality reduction at 28 days (OR 0.25 (0.09–0.68); p = 0.007). Conclusion The median time-to-clearance of procalcitonin and endotoxin was 4 days, and faster clearance was associated with significant mortality reduction. However, patients received additional 12 days of antibiotics. Our new findings support the use of shorter antibiotic courses for patients with bacteremic sepsis. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on the case study of a 79-year old woman with regards to what duration therapy is best for its bacteremia. Topics mentioned include the study that explore the issue on bacteremia treatment in the intensive care unit (ICU) whether a short antibiotic course has better outcome than the long course and the suggestion to critical care practitioners to work with the infectious disease (ID) and antimicrobial stewardship colleagues when protocols are uncertain.

The author discusses study regarding the negative microbiology of patient with hospital-acquired pneumonia (HAP). The author says that the authors performed an observational study and compared negative versus positive microbiology HAP. He states that patient with HAP would have negative microbiology due to the unavailability of respiratory specimen, lack of sputum production, and previous use of antibiotics. He adds that the authors performed a culture methodology to respiratory samples.