Inadequate treatment of ventilator-associated pneumonia: risk factors and impact on outcomes

Teixeira, Paulo José Zimermann; Seligman, Renato; Hertz, Felipe Teixeira; Cruz, Dennis Baroni; Fachel, Jandyra Maria Guimarães

doi:10.1016/j.jhin.2006.12.019

Cited by 66 publications

(46 citation statements)

References 43 publications

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“…These are in-keeping with previous studies (6,9,10,12,13). Underlying diseases, including malignancy, renal disease, immunocompromised status, and hepatic disease, have also been reported as prognostic indicators of hospital mortality (4,10,(14)(15)(16).…”

Section: Discussionsupporting

confidence: 90%

“…The appropriateness and timing of the initial antibiotic therapy is important in reducing VAP mortality. A previous study demonstrated inadequate antibiotic treatment was associated with increased hospital mortality and subsequent change of antibiotic used following sensitivity results did not improve outcomes (13,23). Our findings support previous studies that have shown the use of inappropriate empirical antibiotics, particularly when administered late was a predictor of mortality (10,12,19).…”

Section: Discussionsupporting

confidence: 81%

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Ventilator-Associated Pneumonia: Epidemiology and Prognostic Indicators of 30-Day Mortality

et al. 2015

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SUMMARY:We conducted a retrospective cohort study in the medical intensive care unit of Chaing Mai University Hospital to describe the epidemiology of ventilator-associated pneumonia (VAP) and identify prognostic indicators of 30-day VAP mortality. A total of 621 patients diagnosed with VAP between January 2005 and December 2011 were included. The overall 30-day mortality rate was 44.4z. The major causative pathogens were Acinetobacter baumannii (54.3z), Pseudomonas aeruginosa (35.2z), and methicillin-resistant Staphylococcus aureus (15.1z). Most A. baumannii (90.2z) comprised drug-resistant strains. Identified prognostic indicators were co-morbid malignancy (hazard ratio [HR] ＝ 1.60; 95z confidence interval [CI] 1.02-2.42; P ＝ 0.040), septic shock (HR ＝ 2.51; 95z CI, 1.60-4.00; P ＜ 0.001), Simplified Acute Physiology Score II ＞45 (HR ＝ 1.62; 95z CI, 1.03-2.56; P ＝ 0.041), Sequential Organ Failure Assessment score ＞5 (HR ＝ 3.40; 95z CI 2.00-5.81; P ＜ 0.001), and delayed inappropriate empirical antibiotic treatment (HR ＝ 2.23; 95z CI, 1.12-4.45; P ＝ 0.022). VAP was associated with high mortality. The major causative pathogen was drug-resistant A. baumannii. Therefore, early detection of VAP by surveillance in mechanically ventilated patients leading to earlier treatment may improve patient outcomes. Guidelines for prescribing appropriate empirical antibiotics to cover drug-resistant bacteria could be established using local epidemiological data.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 81%

Ventilator-Associated Pneumonia: Epidemiology and Prognostic Indicators of 30-Day Mortality

et al. 2015

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“…In order to maintain the maximal amount of granulocyte kill, the chemotherapy should generate a bacterial cell kill of 2 to 3 log 10 CFU/ml early on. This is quite concordant with clinical observations, where early, appropriate chemotherapy has a significant impact on the outcome for VAP patients (5,9,10). It also implies that for serious Pseudomonas VAP infections, combination chemotherapy may be the optimal approach.…”

Section: Discussionsupporting

confidence: 83%

Saturability of Granulocyte Kill of Pseudomonas aeruginosa in a Murine Model of Pneumonia

Drusano

VanScoy

Liu

et al. 2011

Antimicrob Agents Chemother

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Outcomes for patients with dense bacterial burdens, such as ventilator-associated pneumonia (VAP) patients, are often critically influenced by the adequacy of antimicrobial chemotherapy and by the response of the immune system, particularly the granulocytes. Little information is available about the quantitation of kill of organisms over time by granulocytes. In this investigation, we examined the impact of the baseline bacterial burden on the ability of granulocytes alone (without chemotherapy) to keep the number of organisms in check or to kill them over a 24-h period. Pseudomonas aeruginosa ATCC 27853 was the study organism, and we employed a murine pneumonia model (granulocyte replete) for the study. We found that the ability of the immune system to kill P. aeruginosa was saturable. The burden at which the system was half saturated was 2.15 ؋ 10 6 ؎ 2.66 ؋ 10 6 CFU/g. Burdens greater than 10 7 CFU/g demonstrated net growth over 24 h. These findings suggest the need for aggressive chemotherapy early in the treatment of VAP to keep the burden from saturating the granulocytes. This should optimize the outcome for these seriously infected patients.We have recently demonstrated that the kill of both Pseudomonas aeruginosa and Staphylococcus aureus by granulocytes is saturable in a mouse thigh infection model in which the animals are granulocyte replete (1). As part of that evaluation, we speculated that the same would be true in the setting of pneumonia and that this phenomenon may explain why some antimicrobial agents that are predicted to be suboptimal based on the exposure achieved at the primary infection site still appear to work, particularly in trials where patients are drawn from the community and where the bacterial burden at the initiation of chemotherapy is modest.While we believed it was likely that the same finding would be demonstrable in the setting of pneumonia, the considerable pathological differences between a murine model reflecting mostly a skin or skin structure type of infection and a murine pneumonia model might be large enough that the findings in the pneumonia model might be substantially different.In this evaluation, we examined the impact of the initial bacterial burden on the ability of granulocytes to limit the expansion of the bacterial population over 24 h in a murine model of Pseudomonas pneumonia. MATERIALS AND METHODSMicroorganisms. Pseudomonas aeruginosa ATCC 27853 was employed. Stocks of the organism were stored in 10% glycerol at Ϫ80°C. The isolate was subcultured on blood agar plates twice before each experiment.Animals. Female 24-to 25-g outbred Swiss Webster mice (Taconic Farms, NY) were used in all in vivo studies. They received food and water ad libitum. All animal experimentation procedures were approved by our Institutional Animal Care and Use Committee (IACUC) and were conducted in accordance with its guidelines.Animal model. Animals were anesthetized with ketamine-xylazine (100 mg/kg ketamine and 6 mg/kg xylazine) via intraperitoneal (i.p.) injection. Pseudomonas aer...

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“…In this prospective study, great efforts were undertaken to control for important host factors through matching for length of hospital admission prior to the onset of infection and adjusting for important confounders, like the severity of disease, making increased vulnerability an improbable explanation. Although it seems likely that administration of inappropriate therapy could lead to higher mortality in MRSA patients (18,39), a recent systematic review (26) argues that this has never been adequately assessed, since detailed analyses that take into account timeliness and drug levels of empirical therapy are still lacking. Moreover, poor interrater agreement on the multiple factors that influence judgments about appropriateness make it difficult to measure (34).…”

Section: Discussionmentioning

confidence: 99%

Clinical Impact of Antimicrobial Resistance in European Hospitals: Excess Mortality and Length of Hospital Stay Related to Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

Kraker

Wolkewitz

Davey

et al. 2011

Antimicrob Agents Chemother

222

105

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. Their excess LOS was 9.2 days. MSSA patients also had higher 30-day (aOR ‫؍‬ 2.4) and hospital (aHR ‫؍‬ 3.1) mortality and an excess LOS of 8.6 days. When the outcomes from the two cohorts were compared, an effect attributable to methicillin resistance was found for 30-day mortality (OR ‫؍‬ 1.8; P ‫؍‬ 0.04), but not for hospital mortality (HR ‫؍‬ 1.1; P ‫؍‬ 0.63) or LOS (difference ‫؍‬ 0.6 days; P ‫؍‬ 0.96). Irrespective of methicillin susceptibility, S. aureus BSI has a significant impact on morbidity and mortality. In addition, MRSA BSI leads to a fatal outcome more frequently than MSSA BSI. Infection control efforts in hospitals should aim to contain infections caused by both resistant and susceptible S. aureus.The emergence of resistant bacteria is a natural consequence of antibiotic use and complicates the treatment of infected patients. Staphylococcus aureus resistant to isoxazolyl penicillins (methicillin-resistant S. aureus [MRSA]) is one of the most frequent pathogens causing resistant infections in hospitals worldwide (14,21,33). The questions are whether and to what extent resistance affects survival and the duration of hospital admission in patients with bacterial infections. Previous studies compared patients with MRSA infections to those infected by methicillin-susceptible S. aureus (MSSA), using mortality as one of the main endpoints. New insights challenge this approach for a number of reasons.Several studies have shown that patients with MRSA bloodstream infection (BSI) differ in many ways from those with MSSA BSI; they are older, have more comorbidities, and experience longer hospital admissions before the onset of infection (6,22,37). If these two groups of patients are compared directly, bias is introduced, compromising the validity of the results. Of all hospitalized patients at risk of acquiring MRSA BSI, the younger, relatively more healthy MSSA patients are selected as the control group, magnifying the possible impact of resistance (20). Moreover, time-dependent distortions are introduced, as patients staying in the hospital for a shorter period, like MSSA patients, have a smaller chance of acquiring MRSA BSI than patients hospitalized for longer periods, who for many reasons are more likely to die, thus leading to overestimation of the clinical impact of resistance (36).

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Inadequate treatment of ventilator-associated pneumonia: risk factors and impact on outcomes

Cited by 66 publications

References 43 publications

Ventilator-Associated Pneumonia: Epidemiology and Prognostic Indicators of 30-Day Mortality

Ventilator-Associated Pneumonia: Epidemiology and Prognostic Indicators of 30-Day Mortality

Saturability of Granulocyte Kill of Pseudomonas aeruginosa in a Murine Model of Pneumonia

Clinical Impact of Antimicrobial Resistance in European Hospitals: Excess Mortality and Length of Hospital Stay Related to Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

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