Empiric Treatment Of Ventilator-associated Pneumonia Research Articles

Which trial do we need? One or two antimicrobials with anti-pseudomonal activity for the empirical treatment of ventilator-associated pneumonia due to Gram-negative bacteria

Which trial do we need? One or two antimicrobials with anti-pseudomonal activity for the empirical treatment of ventilator-associated pneumonia due to Gram-negative bacteria

A STUDY OF BACTERIAL PATTERN OF VENTILATOR ASSOCIATED PNEUMONIA AT A TERTIARY CARE CENTRE OF WESTERN INDIA

Background: Ventilator associated pneumonia (VAP) remains the commonest co-morbid infection in patients admitted to ICU leading to increased morbidity and mortality, despite the technological advancements in health care. Hence, a study of the local bacterial pattern of VAP along with antibiotic sensitivity is essential to frame institutional antibiograms to ensure appropriate empirical treatment of VAP. Aim:The present study aims to study the bacterial pattern of VAP in medical ICUs in a tertiary care center along with the antibiotic sensitivity of the isolates. Method: A descriptive, observational, cross-sectional study was conducted in combined 45 bedded, medical ICUs, at Sawai Man Singh Medical College and Hospital, from March 2020 to 2021. A total of 105 cases were enrolled after application of appropriate exclusion and inclusion criteria from patients on mechanical ventilation for > 48 hours without prior evidence of pneumonia or sepsis. Data regarding demographic and clinical features, laboratory parameters, culture and sensitivity and outcome in terms of death or discharge were collected in a pre-structured proforma and analyzed. Results: Out of the 105 patients evaluated in the study, 71(67.6%) were males. The mean age of the study population was 45.1 years (45.1 17.57) with a range of 18-85 years. Majority were below the age of 40 years (46.7%) followed by those above 60 years (26.7%). The incidence of VAP in the study was 49.5%. Most common co-morbidities underlying patients of VAP was chronic obstructive pulmonary disease (14.3%), coronary artery disease (13.3%), and chronic kidney disease (10.5%). Patients of VAP had a mean temperature of 101.1F (Mean ± SD; 101.1 0.99), along with leukocytosis (Mean ± SD;14399 5373), elevated serum creatinine (Mean ± SD; 1.9 5.9), alanine aminotransferase (Mean ± SD; 84.4 153.7), aspartate aminotransferase (Mean ± SD; 128.7 238.4), and LDH (Mean ± SD; 861.6 690.2), and decreased serum albumin(Mean ± SD; 3.0 0.5). The predominant isolate from endotracheal aspirate culture was Enterobacter species (17.2%), followed by Pseudomonas (15.2), Klebsiella (6.7%), Acinetobacter species (6.7%), and E. coli (4.9%). Those isolated from blood were Enterobacter species (17.2%), followed by Pseudomonas (6.7%), Klebsiella (6.7%), Enterococcus species (5.7%), and coagulase positive S.aureus (5.7%). The antibiotic sensitivity in the study revealed sensitivity predominantly to polymyxin (57.9%) and tigecycline (52.6%) followed by piperacillin-tazobactam (47.4%) and aztreonam (23.7%). The mortality observed in the study was 46.7%. Conclusion: The incidence of VAP in our study was 49.5% attributed to the use of microbiological definition to select cases of VAP and to lack of adequate nursing staff. Most of the isolated organisms isolated from endotracheal aspirate were multidrug resistant organisms sensitive to polymyxin and tigecycline. The mortality observed was also high due to prevalence of multi drug resistance and polymicrobial infection and delay in institution of appropriate antibiotics. Large multicentric studies with large sample size are needed to study the risk factors and their relation in causation of VAP.

Treatment Protocol of Ventilator-Associated Pneumonia based on Microbial Susceptibility in Pediatric Intensive Care Unit, Isfahan, Iran

Background Choosing a unique empiric treatment for ventilator associated pneumonia (VAP) can be challenging. We aimed to determine the antimicrobial susceptibility pattern of Intensive Care Unit (ICU) of the only referral pediatric hospital in Isfahan in order to design the optimal empiric treatment protocol. Materials and Methods: In this cross-sectional study 343 isolates were detected from 243 pediatric patients, from August 2017 to December 2018 in Imam Hossein Hospital, Isfahan, Iran. In suspicious cases of VAP, sampling was performed via non-Bronchoscopic Bronchoalveolar Lavage (NB-BAL). Microbial susceptibility and resistance were assessed. The treatment protocol of VAP was prepared based on existing guidelines. Results: Out of 343 isolates 42 (12.2%) of the positive cultures were Candida albicans and 301 (87.8%) were bacterial isolates. Gram-negative bacteria were the most common organisms with the cumulative percentage of 62.9% of bacterial isolates. When tested with oxacillin, 61.5% of Staphylococcus aureus were MSSA and 38.5% were MRSA. The mentioned common gram-negative organisms had more than 25% resistance to at least one antibiotic from three or more antibiotic classes. However, P. aeruginosa showed below 20% resistance to majority of antibiotics. Twenty-seven (11.1%) of patients had VAP, 25 (92.6%) of whom were gram-negative infections. Conclusion: The limited time period and sample size without any follow-up, made it impossible to define an effective treatment protocol. We defined our antibiogram in accordance with the existing standard guidelines and we designed a local protocol. An effective antibiotic against MRSA should be used in the empiric treatment of VAP. Also, in presence or absence of multidrug-resistant (MDR) pathogen risk-factors, it is necessary to use two effective antipseudomonal antibiotics from different antibiotic classes.

COVID-19: don't neglect antimicrobial stewardship principles!

COVID-19: don't neglect antimicrobial stewardship principles!

Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial

BackgroundColistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined.MethodsA multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7–14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved.ResultsA total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of − 2.16 (− 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015).ConclusionsThis study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination.Trial registrationClinicalTrials.gov, NCT01292031. Registered 9 February 2011.

An Argument for the Use of Aminoglycosides in the Empiric Treatment of Ventilator-Associated Pneumonia.

Appropriate empiric antibiotic therapy for ventilator-associated pneumonia improves outcomes. Controversy exists regarding the inclusion of aminoglycosides in empiric therapeutic regimens. The Ovid and Cochrane databases were searched for relevant literature regarding the use of aminoglycosides in combination therapy for ventilator-associated pneumonia. The data supporting the use of aminoglycosides in certain populations and strategies to limit toxicity are summarized. In patients at high risk of infection with antibiotic-resistant gram-negative bacilli and in those with severe illness, aminoglycosides improve clinical outcomes. In critically ill populations, short-duration therapy and high-dose extended-interval dosing of aminoglycosides can improve therapeutic efficacy while limiting nephrotoxicity. In selected populations using appropriate dosing strategies, aminoglycosides should be considered for empiric treatment of ventilator-associated pneumonia.

Vancomycin Intermittent Dosing versus Continuous Infusion for Treatment of Ventilator-associated Pneumonia in Trauma Patients

Current guidelines for the empiric treatment of ventilator-associated pneumonia (VAP) recommend that vancomycin is dosed 15 mg/kg and administered twice daily for a target trough level of 15 to 20 μg/mL. This study compared conventional intermittent vancomycin infusion (IVI) with continuous vancomycin infusion (CVI). Our prospective, randomized study compared CVI with IVI in trauma patients with suspected VAP. The primary outcome measure was a serum vancomycin level within the target level 48 hours after initiation of therapy. Treatment groups were compared using standard statistical methods. The study included 73 patients, 36 IVI and 37 CVI. Eighteen patients were withdrawn from the study as a result of discontinuation of the drug before 48 hours or failure to draw levels at the appropriate time, resulting in 27 IVI and 28 CVI study patients. There were no differences between treatment groups in gender (P = 0.97), Injury Severity Score (P = 0.70), total body weight (P = 0.36), or age (P = 0.81). The mean serum vancomycin level for the IVI group was 8.9 ± 3.9 μg/mL, and the CVI level was 19.8 ± 6.13 μg/mL (P < 0.0001). Two patients in the IVI group (7.4%) were in the therapeutic range compared with 16 (57.1%) in the CVI group (P < 0.0001). Six patients in the CVI group (21.4%) and none of the IVI patients had supratherapeutic levels. Four patients developed renal insufficiency, three IVI (11.1%) and one CVI (3.6%) (P = 0.36). The current American Trauma Society dosing recommendations for vancomycin for presumptive VAP treatment are inadequate. Continuous vancomycin infusion should be adopted as the standard dosing strategy.

Continuous infusion of piperacillin/tazobactam in ventilator-associated pneumonia: a pilot study on efficacy and costs

Ventilator-associated pneumonia (VAP) occurs in nearly one-third of mechanically ventilated patients in the Intensive Care Unit. Piperacillin/tazobactam (TZP) is currently recommended in the empirical treatment of VAP, but intermittent dosing may result in inadequate serum concentrations. The efficacy and costs of continuous infusion (CI) of TZP, using therapeutic drug monitoring for real-time dose adjustment, was assessed in a prospective pilot study of 16 patients with VAP. TZP was given as a loading dose of 2.0/0.25g followed by a CI of 10.0/1.25g daily. Rapid antimicrobial susceptibility testing was used to determine the minimum inhibitory concentration (MIC) of the pathogens. TZP concentrations were determined by high-pressure liquid chromatography before and at 1, 6, 12, 24, 48, 72 and 96h after the onset of administration. Dosages were adjusted to maintain piperacillin concentrations four-fold above the MIC (T>4×MIC) of the pathogen, with a maximum dose of 16.0/2.0g. The cost of the total TZP administered was compared with the cost of a standard TZP regimen (16.0/2.0g) if given over the same period of time. The median MIC for TZP was 1μg/mL (range 0.025–32μg/mL). TZP concentrations were adequate for 71% of pathogens on the first day of therapy. Clinical cure was achieved in 9/10 patients who had adequate drug concentrations and in 3/6 patients with insufficient levels. The daily dose of TZP received by CI was 37.5% less than that of a standard regimen, which corresponds to a saving of €15 on daily therapy costs compared with the standard regimen. In conclusion, CI of TZP achieved optimal drug concentrations in most patients with VAP, with a favourable impact on costs. Adequate drug concentrations were achieved for MIC≤4μg/mL, but higher dosages should be considered for the treatment of pathogens with low susceptibility thresholds.

Utility of Ampicillin-Sulbactam for Empiric Treatment of Ventilator-Associated Pneumonia in a Trauma Population

Ampicillin-sulbactam is guideline-recommended treatment for early-onset ventilator-associated pneumonia (VAP). However, intensive care unit clinicians are encountering increasing resistance to ampicillin-sulbactam. We sought to analyze the time period for early-onset VAP in our trauma population by using daily evaluation of resistance to ampicillin-sulbactam. A retrospective cohort study was completed on all mechanically ventilated trauma patients admitted to a rural level-1 trauma center from January 2003 to December 2008 who were diagnosed with VAP. Daily bacterial resistance to ampicillin-sulbactam > 15% was defined as the threshold for early empiric antibiotic failure for the first episode of VAP. A univariate analysis of risk factors for multi-drug resistant pathogens (MDRPs) and comorbidities was completed to assess for predisposing factors for ampicillin-sulbactam resistance. One hundred sixty-three pathogens were identified in 121 trauma patients diagnosed with VAP. Of these isolates, 71% were gram-negative, 28% were gram-positive, and 1% was fungal. Methicillin-susceptible Staphylococcus aureus (23.9%), H aemophilus influenzae (20.9%), and Pseudomonas aeruginosa (11.7%) were the most common infecting organisms. Daily ampicillin-sulbactam resistance was 40%, 26%, 32%, 43%, 50%, and 60% on days 3 to 7 and ≥ 8 days, respectively. Only the presence of MDRP risk factors (89% vs. 65%, p < 0.01) and hospital LOS (36.8 [22.8-49.0] vs. 25.7 days [19.0-32.5], p < 0.01) was different between ampicillin- sulbactam resistant and ampicillin-sulbactam susceptible VAP groups. On univariate analysis, hospital length of stay >4 days and antibiotic use within 90 days were associated with ampicillin-sulbactam resistant VAP (p < 0.01). Ampicillin-sulbactam is not an effective empiric therapy for early-onset VAP in our rural trauma population. The utility of ampicillin-sulbactam should be reviewed at other institutions to assess for appropriate empiricism.

COST-BENEFIT MODEL OF EMPIRIC DORIPENEM COMPARED TO IMIPENEM IN VENTILATOR-ASSOCIATED PNEUMONIA

PURPOSE: Inappropriate empiric treatment of ventilator-associated pneumonia (VAP) increases mortality. Pseudomonas aeruginosa (PA), the cause of ¼ of all VAP, is increasingly resistant to conventional antibiotics. The rates of PA-VAP susceptibility to doripenem (DOR) (81.5%) are higher than to imipenem (IMI) (74.1%)[1]. While 7.8% of isolates resistant to IMI are sensitive to DOR (DOR-S), only 0.4% of DOR-resistant PA is sensitive to IMI (IMI-S)[1]. We developed a model to quantify outcome differences between strategies of empiric treatment of VAP with DOR vs. IMI.

Empiric antibiotic therapy for suspected ventilator-associated pneumonia: A systematic review and meta-analysis of randomized trials

To compare specific antibiotic regimens, and monotherapy vs. combination therapy, for the empirical treatment of ventilator-associated pneumonia (VAP). Meta-analysis. Medline, Embase, Cochrane register of controlled trials, study authors, and review articles. We included randomized controlled trials that evaluated empirical parenteral antibiotic regimens for adult patients with clinically suspected VAP. Two independent review groups searched the literature, extracted data, and evaluated trial quality. The primary outcome was all-cause mortality; secondary outcomes included treatment failure. Relative risks were pooled using a random effects model. We identified 41 trials randomizing 7,015 patients and comparing 29 unique regimens. Methodological quality was low, reflecting low rates of complete follow-up (43.9%), use of a double-blinded interventional strategy (14.6%), and randomization concealment (48.6%). Overall mortality was 20.3%; treatment failure occurred in 37.4% of patients who could be evaluated microbiologically. No mortality differences were observed between any of the regimens compared. Only one of three pooled comparisons yielded a significant difference for treatment failure: The combination of ceftazidime/aminoglycoside was inferior to meropenem (two trials, relative risk 0.70, 95% confidence interval 0.53-0.93). Rates of mortality and treatment failure for monotherapy compared with combination therapy were similar (11 trials, relative risk for mortality of monotherapy 0.94, confidence interval 0.76-1.16; and relative risk of treatment failure for monotherapy 0.88, confidence interval 0.72-1.07). Monotherapy is not inferior to combination therapy in the empirical treatment of VAP. Available data neither identify a superior empirical regimen nor conclusively conclude that available regimens result in equivalent outcomes. Larger and more rigorous trials evaluating the choice of, and even need for, empirical therapy for VAP are needed.

A randomized trial of combination therapy versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia

Delays in adequate antibiotic therapy for ventilator-associated pneumonia (VAP) are associated with poor outcomes, and early use of broad-spectrum antibiotics may improve clinical outcomes. However, indiscriminant use of broad-spectrum antibiotics is associated with the emergence of antibiotic-resistant bacteria, fungal infections, and increased healthcare costs. The purpose of this study was to determine optimal empiric treatment of VAP by comparing a strategy of combination therapy to monotherapy with broad-spectrum antibiotics.