G. Christopher Wood

Comparison of ampicillin-sulbactam and imipenem-cilastatin for the treatment of Acinetobacter ventilator-associated pneumonia

Acinetobacter organisms, which are a common cause of ventilator-associated pneumonia (VAP) in some health care centers, are becoming more resistant to such first-line agents as imipenem-cilastatin (Imi-Cil). Sulbactam has good in vitro activity against Acinetobacter organisms; thus, ampicillin-sulbactam (Amp-Sulb) may be a viable treatment alternative. The outcomes for critically ill trauma patients with Acinetobacter VAP treated with either Amp-Sulb or Imi-Cil were compared retrospectively. A total of 77 episodes in 75 patients were studied. Fourteen patients were treated with Amp-Sulb, and 63 patients were treated with Imi-Cil. Treatment efficacy was similar in the Amp-Sulb and Imi-Cil groups (93% vs. 83%, respectively; P>.05). No statistically significant differences between groups were noted with regard to associated mortality, duration of mechanical ventilation, or length of stay in the intensive care unit or hospital. However, adjunctive aminoglycoside therapy was used more often in the Amp-Sulb group. Patients generally received Amp-Sulb because of imipenem resistance. Amp-Sulb was effective in treating a small number of patients with Acinetobacter VAP; however, more data are needed.

Risk Factors for Late-Onset Nosocomial Pneumonia Caused by Stenotrophomonas maltophilia in Critically Ill Trauma Patients

Patients with nosocomial pneumonia caused by Stenotrophomonas maltophilia often receive inadequate empiric antibiotic therapy, potentially increasing mortality. Knowledge of the risk factors associated with S. maltophilia pneumonia may better guide the selection of empiric antibiotic therapy. Potential risk factors for S. maltophilia pneumonia were retrospectively analyzed for critically ill trauma patients with late-onset gram-negative pneumonia. The effects of S. maltophilia infection and inadequate empiric antibiotic therapy on patient outcomes were also assessed. By multivariate analysis, S. maltophilia pneumonia was found to be associated with cefepime exposure and tracheostomy in patients with a single pneumonia episode and with higher Injury Severity Score and pulmonary contusion in patients with multiple pneumonia episodes. S. maltophilia pneumonia was associated with increased patient morbidity; only inadequate empiric antibiotic therapy was associated with a higher mortality rate. In critically ill trauma patients with late-onset ventilator-associated pneumonia and these risk factors, empiric antibiotic therapy should include agents active against S. maltophilia.

Intermittent and continuous Ceftazidime infusion for Critically ill trauma patients

BACKGROUND The adequacy of intermittent and continuous infusion ceftazidime for the treatment of nosocomial pneumonia in critically ill trauma patients was assessed by analyzing ceftazidime pharmacokinetics in relation to the minimum inhibitory concentration (MIC) and treatment outcome. METHODS Serial blood samples were obtained during ceftazidime therapy in 31 trauma patients. Ceftazidime pharmacokinetics were compared with that of previously studied healthy volunteers. Ceftazidime pharmacokinetics were analyzed according to the time above the MIC and treatment outcome. RESULTS Critically ill trauma patients had a significantly increased volume of distribution and clearance (0.32 +/- 0.14 L/kg and 2.35 +/- 0.89 mL. min(-1). kg(-1), respectively) compared with healthy volunteers (0.21 +/- 0.03 and 1.58 +/- 0.23 mL. min(-1). kg(-1)). The time above the MIC was >/=92% of the dosing interval for all patients and treatment outcomes were similar between the two treatment groups. CONCLUSIONS Ceftazidime pharmacokinetics are significantly altered in critically ill trauma patients. Both intermittent and continuous ceftazidime regimens were equally effective for the treatment of nosocomial pneumonia caused by less virulent bacteria.

Effect from multiple episodes of inadequate empiric antibiotic therapy for ventilator-associated pneumonia on morbidity and mortality among critically ill trauma patients.

BACKGROUND Empiric antibiotic therapy is routinely initiated for patients with presumed ventilator-associated pneumonia (VAP). The impact of inadequate empiric antibiotic therapy (IEAT) may vary among critically ill populations. The purpose of this retrospective study was to determine the effect of IEAT on the outcome for adult trauma patients with VAP. METHODS This study enrolled 82 patients with multiple VAP episodes (200 VAP episodes; mean, 2.4 +/- 0.65 per patient; range, 2-5 episodes). An episode of IEAT was a VAP episode with empiric therapy having no in vitro activity against causative bacteria. Overall, there were 78 (39%) IEAT episodes involving 54 patients. Most often, IEAT was attributable to the presence of Acinetobacter spp, Stenotrophomonas maltophilia, or Alcaligenes xylosoxidans. All the patients received appropriate definitive therapy according to the final culture. The patients were classified by number of IEAT episodes: 0 (n = 28), 1 (n = 34), and more than 1 (n = 20). RESULTS Demographics and injury severity were similar among the groups. The mortality rate was 3.6% for no episodes, 8.8% for one episode, and 45% for more than one episode (p < 0.001). On the basis of multiple logistic regression, experiencing multiple IEAT episodes was independently associated with the risk of death (odds ratio, 4.28; 95% confidence interval, 1.44-12.71). Additionally, experiencing multiple IEAT episodes was associated with prolonged intensive care unit stay (p = 0.007) and prolonged mechanical ventilation (p = 0.005). CONCLUSIONS Critically ill trauma patients experiencing multiple episodes of IEAT for VAP have increased morbidity and mortality. These findings reinforce the importance of developing and refining a unit-specific pathway for the empiric management of VAP.

Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients

Study Objectives. To evaluate the safety and efficacy of aerosolized ceftazidime for prevention of ventilator‐associated pneumonia (VAP) and to evaluate the effects of the drug on the proinflammatory response.

The appropriate diagnostic threshold for ventilator-associated pneumonia using quatititative cultures

BACKGROUND The use of quantitative cultures of the bronchoalveolar lavage (BAL) effluent to distinguish between posttraumatic inflammatory response and ventilator-associated pneumonia (VAP) is becoming more common. However, the diagnostic threshold of either 10 or 10 colonies/mL remains debatable. Because mortality from VAP is related to treatment delay, some have chosen a lower diagnostic threshold (>10 colonies/mL). This may result in unnecessary antibiotic use with its sequelae: increased resistant organisms, antibiotic-related complications, and increased costs. The purpose of this study is to determine the optimal diagnostic threshold for VAP diagnosis using quantitative cultures of the BAL effluent. METHODS Data on patients with fiberoptic bronchoscopy with BAL are maintained in a prospectively collected database at our Level I trauma center. This database was reviewed for timing and frequency of BAL and the colony counts of each organism identified. Indication for bronchoscopy was clinical evidence of VAP. VAP was defined as >10 colonies/mL in the BAL effluent. A false-negative BAL was defined as any patient who had <10 colonies/mL and developed VAP with the same organism up to 7 days after the previous culture. RESULTS Over a 46-month period, 526 patients underwent 1,372 fiberoptic bronchoscopy procedures with BAL. Of these, 72% were male patients, 91% followed blunt injury, and mean age and Injury Severity Score were 43 years and 30, respectively. Overall mortality was 14%. There were 1,898 organisms identified (42% were gram-positive and 58% were gram-negative). VAP was diagnosed in 38% of BAL. Overall, there were 43 episodes in 38 patients defined as false-negative (3%). The false-negative rate was 9% in patients with 10 organisms. The most common false-negative organisms were Pseudomonas and Acinetobacter species. CONCLUSION The VAP diagnostic threshold for quantitative BAL in trauma patients should be >10 colonies/mL. One may consider a threshold of >10 colonies/mL in severely injured patients with Pseudomonas or Acinetobacter species.

Consensus summary of aerosolized antimicrobial agents: application of guideline criteria. Insights from the Society of Infectious Diseases Pharmacists.

Aerosolized delivery of antimicrobial agents is an attractive option for management of pulmonary infections, as this is an ideal method of providing high local drug concentrations while minimizing systemic exposure. With the paucity of consensus regarding the safety, efficacy, and means with which to use aerosolized antimicrobials, a task force was created by the Society of Infectious Diseases Pharmacists to critically review and evaluate the literature on the use of aerosolized antiinfective agents. This article summarizes key findings and statements for preventing or treating a variety of infectious diseases, including cystic fibrosis, bronchiecstasis, hospital acquired pneumonia, fungal infections, nontuberculosis mycobacterial infection, and Pneumocystis jiroveci pneumonia. Our intention was to provide guidance for clinicians on the use of aerosolized antibiotics through evidence based pharmacotherapy. Further research with well designed clinical trials is necessary to elucidate the optimal dosage and duration of therapy and, of equal importance, to appreciate the true risks associated with the use of aerosolized delivery systems.

Aerosolized antibiotics for treating hospital-acquired and ventilator-associated pneumonia.

Hospital-acquired pneumonia is a common complication that continues to have a poor cure rate in some patients with intravenous therapy alone. Aerosolized antibiotics are theoretically attractive in an attempt to optimize lung concentrations of antibiotics. Limited data suggest that aerosolized aminoglycosides or colistin in addition to intravenous therapy results in good response rates in patients with multidrug-resistant organisms or nonresponding pneumonia. Adverse events can occur, especially with colistin. When used, care should be taken to properly compound and administer aerosolized antibiotics to ensure tolerability and good drug delivery.

Adjunctive aerosolized antibiotics for treatment of ventilator-associated pneumonia.

Study Objective. To determine clinical and microbiologic success in patients receiving adjunctive aerosolized antibiotics for the treatment of ventilator‐associated pneumonia (VAP).

Repeat bronchoalveolar lavage to guide antibiotic duration for ventilator-associated pneumonia.

BACKGROUND Using an arbitrary day cutoff or clinical signs to decide the duration of antibiotic therapy for ventilator-associated pneumonia (VAP) may be suboptimal for some patients. We sought to determine whether antibiotic duration for VAP can be safely abbreviated in trauma patients using repeat bronchoalveolar lavage (BAL). METHODS This was an observational case-controlled pilot study. Fifty-two patients were treated for VAP using a repeat BAL clinical pathway. Definitive antibiotic therapy for VAP was discontinued if pathogen growth was <10,000 colony forming units/mL on repeat BAL performed on day 4 of antibiotic therapy (responder), otherwise therapy was continued per managing team. A matched control group of 52 VAP patients treated before (immediately consecutive) the pathway was used for comparison. RESULTS Antibiotic duration in pathway patients was shorter than control patients (9.8 days +/- 3.8 days vs. 16.7 days +/- 7.4 days; p < 0.001), including nonfermenting gram-negative bacilli VAP (10.7 days +/- 4.1 days vs. 14.4 days +/- 4.2 days; p < 0.001). There were no differences in pneumonia relapse, mechanical ventilator-free intensive care unit (ICU) days, ICU-free hospital days, or mortality. Of study group isolates, 86 (82.7%) responded on repeat BAL and were treated for 8.8 days +/- 3.3 days. Of these without concomitant infections (n = 65), antibiotic duration was 7.3 days +/- 1.2 days compared with 14.4 days +/- 2.6 days for nonresponding isolates (n = 18) (p < 0.001). CONCLUSIONS Repeat BAL decreased the duration of antibiotic therapy for VAP in trauma patients. More adequately powered investigations are needed to appropriately determine the effects of this strategy on patient outcome.