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Effectiveness of adjunctive nebulized antibiotics in critically ill patients with respiratory tract infections.

ABSTRACT: The purpose of the study was to analyze the effectiveness of adding nebulized antibiotics to systemic antimicrobials in critically ill patients with respiratory tract infections (pneumonia or tracheobronchitis) and the effect on renal function. A retrospective observational cohort study including critically ill patients with respiratory tract infections during a 2-year period was conducted. Intervention group included patients that received nebulized and systemic antimicrobials. Patients in the control group received only systemic antimicrobials. Clinical resolution was the primary endpoint. Secondary outcomes included change in fever, inflammatory parameters, and creatinine clearance; length of hospital stay, systemic therapy, and mechanical ventilation; hospital readmission; and mortality. Regression models were performed to estimate the effect of nebulized antibiotics on outcome variables adjusted by potential confounders. A total of 136 patients were included (93 in control group and 43 in intervention group). The intervention group had higher odds of clinical resolution (adjusted odds ratio (OR): 7.1; 95% confidence interval (95% CI): 1.2, 43.3). Nebulized antibiotic therapy was independently associated with reduction in procalcitonin (adjusted OR: 12.4; 95% CI: 1.4, 109.7). There were no significant differences in the rest of the secondary outcomes or in creatinine clearance reduction. Adding nebulized antibiotics for the management of respiratory tract infections has a positive impact on clinical resolution without increasing the risk of renal toxicity.

SUBMITTER: Leache L

PROVIDER: S-EPMC7223945 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Inhaled antibiotics have been used as adjunctive therapy for patients with pneumonia, primarily caused by multidrug resistant (MDR) pathogens. Most studies have been in ventilated patients, although non-ventilated patients have also been included (but not discussed in this review), and most patients have had nosocomial pneumonia. Aerosolized antibiotics are generally added to systemic therapy, and have shown efficacy, primarily as salvage therapy for failing patients and as adjunctive therapy after an MDR gram-negative has been identified. An advantage to aerosolized antibiotics is that they can achieve high intra-pulmonary concentrations that are potentially effective, even for highly resistant pathogens, and because they are generally not well-absorbed systemically, it is possible to avoid some of the toxicities of systemic therapy. When using inhaled antibiotics, it is essential to choose the appropriate agent and the optimal delivery method. Animal and human studies have shown that aerosolized antibiotics reach higher concentrations in the lung than systemic antibiotics, but that areas of dense pneumonia may not receive as much antibiotic as less affected areas of lung. Optimal delivery in ventilated patients depends on device selection, generally with a preference for vibrating mesh nebulizers and with careful attention to where the device is placed in the ventilator circuit and how the delivery is coordinated with the ventilator cycle. Although some studies have shown a benefit for clinical cure, adjunctive therapy has not led to reduced mortality. In some studies, adjunctive aerosol therapy has reduced the duration of systemic antibiotic therapy, thus serving to promote antimicrobial stewardship. Two recent multicenter, randomized, double-blinded, placebo-controlled trials of adjunctive nebulized antibiotics for VAP patients with suspected MDR gram-negative pneumonia were negative for their primary endpoints. This may have been related to trial design and execution and the lessons learned from these studies need to be incorporated in any future trials. Currently, routine use of adjunctive aerosolized therapy cannot be supported by available data, and this therapy is only recommended to assist in the eradication of highly resistant pathogens and to be used as salvage therapy for patients failing systemic therapy.

Project description:BackgroundUnlike other viruses, the pathogenicity of human metapneumovirus (hMPV) in adults remains uncertain. To address this question, a retrospective monocentric cohort including all patients admitted to ICU with hMPV infection between January 1, 2010, and June 30, 2018 was performed. The characteristics of hMPV infected patients were studied and compared to matched influenza infected patients. Consecutively, a systematic review and meta-analyses investigating PUBMED, EMBASE and COCHRANE databases was conducted to explore the hMPV infections in adult patients (PROSPERO number: CRD42018106617). Trials, case series, and cohorts published between January 1, 2008 and August 31, 2019 compiling adults presenting hMPV infections were included. Pediatric studies were excluded. Data were extracted from published reports. Primary endpoint was the rate of low respiratory tract infections (LRTIs) among all hMPV infected patients.ResultsDuring the study period, 402 patients were tested positive for hMPV. Among them 26 (6.5%) patients were admitted to the ICU, 19 (4.7%) for acute respiratory failure. Twenty-four (92%) were immunocompromised. Bacterial coinfections were frequent 53.8%. Hospital mortality rate was 30.8%. In the case-control analysis, the clinical and imaging characteristics were not different between hMPV and influenza infected patients. The systematic review identified 156 studies and 69 of them (1849 patients) were eligible for analysis. Although there was heterogeneity between the studies, the rate of hMPV LRTIs was 45% (95% CI 31-60%; I2 = 98%). Intensive care unit (ICU) admission was required for 33% (95% CI 21-45%; I2 = 99%). Hospital mortality rate was 10% (95% CI 7-13%; I2 = 83%) and ICU mortality rate was 23% (95% CI 12-34%; I2 = 65%). Underlying malignancy was independently associated with increased mortality rate.ConclusionsThis preliminary work suggested that hMPV may be associated with severe infection and high mortality in patients with underlying malignancies. However, regarding the small size of the cohort and the heterogeneity of the review, more cohort studies are warranted.

Project description:Lower respiratory tract infections (LRTIs) are a major cause of morbidity and death. Because of changes in how LRTIs are defined coupled with the increasing prevalence of drug resistance, there is a gap in knowledge regarding the current burden of antimicrobial use for Centers for Disease Control and Prevention (CDC)-defined LRTIs. We describe the infection characteristics, antibiotic consumption, and clinical and economic outcomes of patients with Gram-negative (GN) LRTIs treated in intensive care units (ICUs).This was a retrospective, observational, cross-sectional study of adult patients treated in ICUs at two large academic medical centers in metropolitan Detroit, Michigan, from October 2013 to October 2015. To meet the inclusion criteria, patients must have had CDC-defined LRTI caused by a GN pathogen during ICU stay. Microbiological assessment of available Pseudomonas aeruginosa isolates included minimum inhibitory concentrations for key antimicrobial agents.Four hundred and seventy-two patients, primarily from the community (346, 73.3%), were treated in medical ICUs (272, 57.6%). Clinically defined pneumonia was common (264, 55.9%). Six hundred and nineteen GN organisms were identified from index respiratory cultures: P. aeruginosa was common (224, 36.2%), with 21.6% of these isolates being multidrug resistant. Cefepime (213, 45.1%) and piperacillin/tazobactam (174, 36.8%) were the most frequent empiric GN therapies. Empiric GN therapy was inappropriate in 44.6% of cases. Lack of in vitro susceptibility (80.1%) was the most common reason for inappropriateness. Patients with inappropriate empiric GN therapy had longer overall stay, which translated to a median total cost of care of $79,800 (interquartile range $48,775 to $129,600) versus $68,000 (interquartile range $38,400 to $116,175), p = 0.013. Clinical failure (31.5% vs 30.0%, p = 0.912) and in-hospital all-cause mortality (26.4% vs 25.9%, p = 0.814) were not different.Drug-resistant pathogens were frequently found and empiric GN therapy was inappropriate in nearly 50% of cases. Inappropriate therapy led to increased lengths of stay and was associated with higher costs of care.

Project description:The potential relationship among airway Candida spp. de-colonization, nebulized amphotericin B (NAB), and occurrence of ventilator-associated pneumonia (VAP) in patients who are critically ill has not been fully investigated, especially concerning effects on survival. In this observational, retrospective, cohort study in a 22-bed central intensive care unit, we included patients aged >18 years who required mechanical ventilation (MV) for >48 h, with at least two consecutive positive Candida spp. test results. Patients were categorized into NAB and no NAB (control) groups. Propensity matching at 1:1 was performed according to strict standards, and multiple Cox proportional hazard model and multivariate analyses were performed to evaluate the effects of NAB treatment. Throughout an 8-year study period, 526 patients had received MV and had positive respiratory tract Candida spp. cultures. Of these, we included 275 patients and excluded 251 patients. In total, we successfully matched 110 patients from the two groups (each group, n = 55; total population median age, 64 years; Acute Physiology and Chronic Health Evaluation II [APACHE II] score, 25.5; sequential organ failure assessment score, 9). The Candida spp. de-colonization rate was 69.1% in patients treated with NAB. VAP incidence did not differ significantly between the NAB (10.91%) and control (16.36%) groups (P = 0.405). Pseudomonas aeruginosa-related VAP rates differed significantly between the NAB (10.91%) and control (25.45%) groups (P = 0.048). Five (9.1%) patients in the NAB group died during hospitalization compared with 17 (30.9%) controls (P = 0.014). At 28 days, 9 (16.4%) and 16 (29.1%) deaths occurred in the NAB and control groups, respectively, (P = 0.088). The cumulative 90-day mortality rate differed significantly between the two groups (23.6 vs. 43.6%, P = 0.015). Multivariate logistic regression analyses indicated a decreased 90-day mortality in the NAB group (adjusted odds ratio 0.413; 95% confidence interval 0.210-0.812; P = 0.01). In subgroup analyses, the NAB-associated decreased risk of death at 90 days was consistent across subgroups of patients with a Candida score of 2, younger age (<64 years), a higher APACHE II score (≥25), fewer Candida sites (<2), or MV at admission. NAB treatment contributed to Candida spp. airway de-colonization, was associated with a reduced risk of P. aeruginosa-related VAP, and improved 90-day mortality in patients critically ill with Candida spp. tracheobronchial colonization who had received MV for >2 days. NAB may be an alternative treatment option for critically ill patients with VAP.

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Effectiveness of adjunctive nebulized antibiotics in critically ill patients with respiratory tract infections.

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