Antimicrobial Therapy For Ventilator-associated Pneumonia Research Articles

Predictors and microbiology of ventilator-associated pneumonia among patients with exacerbation of chronic obstructive pulmonary disease.

Background:Understanding the risk factors and microbiology of ventilator-associated pneumonia (VAP) among patients with chronic obstructive pulmonary disease (COPD) is important for the application of preventive and therapeutic interventions. Therefore, this study was planned to assess the clinical predictors and microbiological features of VAP among COPD patients.Materials and Methods:This prospective study involved patients with exacerbation of COPD who required mechanical ventilation and admitted in respiratory intensive care unit at a tertiary care teaching hospital. Various baseline demographic and clinical features were compared between patients with VAP and without VAP. Univariate and multivariable analyses were done to assess the impact of demographic and clinical features on the development of VAP.Results:The study included 100 intubated patients with age (mean ± standard deviation [SD]) of 62.45 ± 8.32 years, duration (median) of COPD of 6 years, and Acute Physiology, Age, and Chronic Health Evaluation score (mean ± SD) of 18.60 ± 4.30. In this cohort, 17 patients developed VAP. Multivariable analysis showed that Sequential Organ Failure Assessment (SOFA) score at admission, re-intubation, and history of previous hospitalization were independent predictors of VAP with odds ratio (95% confidence interval) of 2.70 (1.24, 5.63; P = 0.012), 66.96 (4.86, 922.72; P = 0.002), and 35.92 (2.84, 454.63; P = 0.006), respectively. Acinetobacter baumannii was the most frequent organism (n = 8; 47%), followed by Klebsiella pneumoniae (n = 5; 29%), Pseudomonas aeruginosa (n = 1; 6%), and Enterobacter spp. (n = 1; 6%). All organisms were multidrug resistant (MDR).Conclusions:SOFA score at admission, re-intubation, and history of previous hospitalization were independent predictors of VAP. Antimicrobial therapy for VAP should cover MDR Gram-negative organisms.

Empiric antimicrobial therapy for ventilator-associated pneumonia after brain injury.

Issues regarding recommendations on empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) have emerged in specific populations.To develop and validate a score to guide empiric therapy in brain-injured patients with VAP, we prospectively followed a cohort of 379 brain-injured patients in five intensive care units. The score was externally validated in an independent cohort of 252 brain-injured patients and its extrapolation was tested in 221 burn patients.The multivariate analysis for predicting resistance (incidence 16.4%) showed two independent factors: preceding antimicrobial therapy ≥48 h (p<0.001) and VAP onset ≥10 days (p<0.001); the area under the receiver operating characteristic curve (AUC) was 0.822 (95% CI 0.770-0.883) in the learning cohort and 0.805 (95% CI 0.732-0.877) in the validation cohort. The score built from the factors selected in multivariate analysis predicted resistance with a sensitivity of 83%, a specificity of 71%, a positive predictive value of 37% and a negative predictive value of 96% in the validation cohort. The AUC of the multivariate analysis was poor in burn patients (0.671, 95% CI 0.596-0.751).Limited-spectrum empirical antimicrobial therapy has low risk of failure in brain-injured patients presenting with VAP before day 10 and when prior antimicrobial therapy lasts <48 h.

Impact of Pathogen-Directed Antimicrobial Therapy for Ventilator-Associated Pneumonia in Trauma Patients on Charges and Recurrence

Ventilator-associated pneumonia (VAP) represents one of the driving forces behind antibiotic use in the ICU. In a previous study, we established a defined algorithm for treatment of hospital-acquired VAP dictated by the causative pathogen. The purpose of the current study was to evaluate the impact of this algorithm for hospital-acquired VAP on recurrence and charges in trauma patients. Patients with VAP secondary to MRSA, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or Enterobacteriaceae during 5 years subsequent to the previous study were evaluated. All VAP were diagnosed using quantitative cultures of the bronchoalveolar lavage effluent. Duration of antimicrobial therapy was dictated by the causative pathogen. If microbiologic resolution, defined as <10(3) colony-forming units/mL, was achieved, therapy was stopped by day 10. The remainder received 14 days of therapy. Recurrence was defined as >10(5) colony-forming units/mL on subsequent bronchoalveolar lavage performed within 2 weeks after completion of appropriate therapy. Five hundred and twenty-nine VAP episodes were identified in 381 patients. Overall recurrence was unchanged compared with the previous study (1.5% vs 2%; p = 0.3). There was a decrease in the number of bronchoalveolar lavages performed per patient compared with the previous study (1.6 vs 2.3; p = 0.24) and a reduction of 4.8 antibiotic days per VAP episode compared with the previous study. Both changes resulted in a cumulative reduction of $3,535.04 per patient, for a savings of $1.35 million during the study period. Hospital-acquired VAP can be managed effectively by a defined course of therapy dictated by the causative pathogen. Adherence to an established algorithm simplified the management of VAP and contributed to a cumulative reduction in patient charges without impacting recurrence.

Acinetobacter is the most common pathogen associated with late-onset and recurrent ventilator-associated pneumonia in an adult intensive care unit in Saudi Arabia

The guidelines for initial empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) are highly dependent on the type of causative pathogen and the time of diagnosis. The objective of this study was to examine the microbial causes of VAP and describe any variability by the timing of VAP onset and over time. A prospective surveillance study was conducted in the adult general intensive care unit of a tertiary care hospital in Riyadh, Saudi Arabia. Microbial isolates obtained from blood and different respiratory specimens of patients diagnosed with VAP (using the US Centers for Disease Control and Prevention definition) between August 2003 and June 2009 were included. A total of 457 pathogens were identified during the study; 380 (83.2%) were associated with primary VAP and 77 (16.8%) were associated with recurrent VAP. Of primary VAP pathogens, 159 (41.8%) were associated with early-onset (<5 days) and 221 (58.2%) were associated with late-onset (≥5 days) VAP. The most common pathogen identified was Acinetobacter spp (26.5%), followed by Pseudomonas aeruginosa (21.7%), Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) (15.3%), Klebsiella spp (6.8%), Haemophilus spp (6.1%), and Enterobacter spp (5.0%). Acinetobacter spp and MRSA were significantly associated with late-onset VAP while Haemophilus spp and Streptococcus pneumoniae were significantly associated with early-onset VAP. Acinetobacter spp was the only pathogen associated with recurrent VAP and its incidence showed a significant increasing trend during the study period. Acinetobacter spp was significantly associated with prolonged ventilation, sedation, and nasogastric intubation. Acinetobacter baumannii is the most common and increasingly important pathogen associated with VAP in our patients, especially late-onset and recurrent VAP.

Identifying Missed Opportunities to Curtail Antimicrobial Therapy for Presumed Ventilator-Associated Pneumonia Using the Clinical Pulmonary Infection Score

Early discontinuation of antimicrobial therapy for ventilator-associated pneumonia can reduce the emergence of antimicrobial resistance, the occurrence of adverse drug events, and the cost of therapy. Evidence suggests that discontinuation of therapy by day 3 may be appropriate for patients with a clinical pulmonary infection score of 6 or less at baseline and on day 3. To determine the proportion of patients eligible for antimicrobial discontinuation on day 3 and day 7 of therapy and to determine the proportion of eligible patients for whom antimicrobials were discontinued within these timeframes. A 6-month observational study was conducted from October 3, 2005, to March 31, 2006, in a 27-bed medical-surgical tertiary care intensive care unit. Clinical pharmacists attended daily rounds and prospectively identified patients for inclusion in the study. A study pharmacist retrospectively calculated clinical pulmonary infection scores. Other data were obtained from the quality-improvement database and patient health records for the intensive care unit. Ninety-two patients were treated for ventilator-associated pneumonia during the study period, of whom 49 were included in the analysis. At day 3, 17 (35%) of the 49 patients were eligible for early discontinuation of antimicrobial therapy, but therapy was discontinued for only 2 (12%) of these 17 patients. At day 7, 10 (32%) of 31 patients were eligible for antimicrobial discontinuation, but therapy was discontinued for only 1 (10%) of these 10 patients. A significant opportunity exists at the authors' institution to develop and implement an antimicrobial discontinuation policy that uses the clinical pulmonary infection score to guide antimicrobial use for patients with ventilator-associated pneumonia.

Ventilator-associated pneumonia: Breaking the vicious circle of antibiotic overuse*

To assess the rate of appropriateness of empirical antimicrobial therapy for ventilator-associated pneumonia, to evaluate de-escalation in patients with ventilator-associated pneumonia treated according to local pathway, and to identify the bacteria responsible for recurrence of ventilator-associated pneumonia. Prospective observational study during a 36-month period. Medical-surgical intensive care unit of a university hospital. One hundred and fifteen patients hospitalized in an intensive care unit developing ventilator-associated pneumonia with positive cultures. The patients with ventilator-associated pneumonia were treated with limited-spectrum antibiotics (i.e., without activity against Pseudomonas aeruginosa) if they had no prior hospitalization (within 21 days) or prior administration of antibiotics (within 10 days). Quantitative cultures obtained by bronchoscopy or tracheal aspiration were used to reassess empirical therapy. None. A limited-spectrum therapy was used in 79 patients (69%). Empirical antimicrobial therapy was appropriate in 100 patients (85%). The mortality rate was significantly higher in the patients in whom empirical therapy was inappropriate than in those in whom treatment was appropriate (47 vs. 20%, p=.04). De-escalation was done in respectively 26% and 72% of patients with early- and late-onset ventilator-associated pneumonia, whereas treatment was escalated in 27 patients (23%). Ventilator-associated pneumonia episodes were recurrent in 22 cases, including eight episodes due to high-risk bacteria. A rational empirical antimicrobial therapy for ventilator-associated pneumonia using limited-spectrum antibiotics is possible if local ecology and patient medical history and clinical status are considered. In addition, de-escalation is feasible in 42% of patients. This integrative approach may reduce the emergence of resistant bacteria, which in turns reduces the need for broad-spectrum antibiotics, breaking the vicious circle of antibiotic overuse.

Use of Broad-Spectrum Antimicrobials for the Treatment of Pneumonia in Seriously Ill Patients: Maximizing Clinical Outcomes and Minimizing Selection of Resistant Organisms

Among various risk factors for death among critically ill patients with serious infection, inappropriate antimicrobial therapy is an important factor that clinicians can modify directly. The presence of multidrug-resistant bacteria is the primary reason that patients with ventilator-associated pneumonia receive inappropriate antimicrobial therapy. Empirical antimicrobial therapy for ventilator-associated pneumonia should be initiated promptly and should have a broad spectrum that covers all potential antimicrobial-resistant pathogens. Delaying the start of therapy or modifying an inappropriate antimicrobial regimen does not improve outcome, probably because the change comes too late to redirect the course of illness. Timely empirical therapy with highly effective agents that are rapidly bactericidal could minimize the emergence of resistance. Broad-spectrum therapy should be streamlined (i.e., de-escalated), as appropriate, on the basis of microbiological data and clinical response. Switching to narrower-spectrum therapy that is directed by culture results may minimize the emergence of resistance. For some patients, clinical response will allow a shortening of the duration of antimicrobial therapy.

Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia.

Although recommended durations of antimicrobial therapy for ventilator-associated pneumonia (VAP) range from 7 to 21 d, these are not based on prospective studies and little is known about the resolution of symptoms after start of antibiotics. Resolution of these symptoms was investigated in 27 patients. VAP was diagnosed on clinical, radiographic, and microbiological criteria, including quantitative cultures of bronchoalveolar lavage. All patients received appropriate antibiotic therapy. Highest temperatures, leukocyte counts, Pa(O(2))/FI(O(2)) ratios, and semiquantitative cultures of endotracheal aspirates were recorded from start of therapy until Day 14. Resolution was defined as the first day that these parameters fulfilled the following definition: temperature < or = 38 degrees C, leukocytes < or = 10 x 10(9)/L, Pa(O(2))/FI(O(2)) ratio > or = 25 kPa, and no or +1 of bacterial growth of etiologic pathogens in cultures of endotracheal aspirate. VAP was caused by Enterobacteriaceae (n = 14), P. aeruginosa (n = 7), S. aureus (n = 6), H. influenzae (n = 3), and S. pneumoniae (n = 1). H. influenzae and S. pneumoniae were eradicated from tracheal aspirates, whereas Enterobacteriaceae, S. aureus, and P. aeruginosa persisted, despite in vitro susceptibility to antibiotics administered. Significant improvements were observed for all clinical parameters, most apparently within the first 6 d after start of antibiotics. Newly acquired colonization, especially with P. aeruginosa and Enterobacteriaceae, occurred in the second week of therapy. Six patients developed a recurrent episode of VAP, four of them with P. aeruginosa. Clinical responses to therapy for VAP occur within the first 6 d of therapy, endotracheal colonization with Gram-negative bacteria persists despite susceptibility to therapy, and acquired colonization usually occurs in the second week of therapy and frequently precedes a recurrent episode.

Single versus combination antimicrobial therapy for ventilator-associated pneumonia

The appropriate selection of definitive antimicrobial therapy is a necessary component of the overall treatment for ventilator-associated pneumonia. When possible, single-agent therapy is preferable. A combination of antibiotics is necessary to treat multiple organisms not susceptible to a single appropriate antibiotic and when antibiotic-resistant gram-negative bacteria are present. Treatment failure is more commonly the result of persistent pneumonia and the development of antibiotic resistance than to recurrence after successful antimicrobial therapy. The duration of treatment will vary depending on the severity of the underlying illness and the pneumonic process.

Follow-up Protected Specimen Brushes to Assess Treatment in Nosocomial Pneumonia

To prospectively determine the bacteriologic and clinical efficacy of antimicrobial therapy for nosocomial bacterial pneumonia selected based upon information provided by cultures of protected specimen brush (PSB) samples obtained during bronchoscopy, 76 consecutive patients with ventilator-associated pneumonia were studied using follow-up quantitative PSB cultures obtained after 3 days of treatment. Of the 173 microorganisms initially present in the PSB samples, only 11 (6%) were not eradicated by antimicrobial therapy, including three recovered at high (> or = 10(3) cfu/ml) concentrations. Thirty-two emerging pathogens, including nine at high concentrations, were also detected; 26 of them (81%) were resistant to the initial antibiotics administered. Of the 76 patients included in the study, cultures of follow-up PSB samples identified 51 in whom the infection site in the lung was completely sterilized, 16 with low-grade infection, and only nine with persistent high-grade infection. Analysis of clinical outcome within the 15 days after the initiation of antimicrobial therapy demonstrated clinical improvement in 62 of 67 (93%) patients in whom the site of infection was contained by treatment as compared with four of 9 (44%) patients with persistent high-grade infection (p < 0.01). These data suggest that appropriate antimicrobial therapy for ventilator-associated pneumonia results in the control of the initial infection in 88% of the patients. However, an early superinfection caused by multiresistant pathogens can occur in a small subset of these patients. When follow-up PSB cultures were negative, an improved outcome was noted.