Scott D. Hanes

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.

Incidence and risk factors of thrombocytopenia in critically ill trauma patients.

Objective To determine the incidence of thrombocytopenia (<100 platelets × 103/mm3) and potential risk factors, including medications, associated with the development of thrombocytopenia in critically ill trauma patients. Design Prospective, observational study. Setting A 20-bed trauma intensive care unit (ICU) at a university hospital. Patients Sixty-three critically ill trauma patients without baseline thrombocytopenia admitted to the trauma ICU for at least 48 hours. Interventions Patients were followed for up to 14 days. Platelet counts were determined daily. The following data were collected and analyzed as potential risk factors for the development of thrombocytopenia: medications, age, sex, race, trauma score, mode and type of injury, alcohol history, units of packed red blood cells (PRBC) and platelets transfused, surgical procedures, duration of ICU stay, and the development of systemic inflammatory response syndrome or disseminated intravascular coagulation. Results Thrombocytopenia occurred in 26 (41%) of the patients. Among risk factors studied, nonhead injury, age, trauma score, duration of ICU stay, and the number of PRBC transfusions were significanüy associated with the development of thrombocytopenia (P < 0.05). However, nonhead injury, age, and trauma score were useful variables in predicting the development of thrombocytopenia by using multivariate analysis. Medications were not associated with the development of thrombocytopenia. Conclusions The type of injury sustained, the quantity of platelet-deficient transfusions, and age are the greatest risk factors associated with the development of thrombocytopenia in critically ill trauma patients. Drug-induced thrombocytopenia appears to play a minor role in the development of thrombocytopenia; therefore, medications should not be automatically discontinued or substituted when thrombocytopenia occurs.

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.

Hepatic drug metabolism in critical illness

Hepatic drug metabolism is altered in critically ill patients. The etiology and mechanisms of the alterations are not clearly understood and are difficult to address in clinical studies. For this reason, in vitro and animal models were developed to investigate the effects of critical illness on hepatic drug metabolism. Specifically, those with sepsis, septic shock, hemorrhagic shock, trauma, neurotrauma, and burns are populations that have been studied. Most of this research, however, has not led to established guidelines for the administration of drugs in these populations.

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.

Alternative method for determination of ceftazidime in plasma by high-performance liquid chromatography

A high-performance liquid chromatography procedure was developed to analyze ceftazidime concentrations in plasma. The procedure consisted of solid phase extraction followed by ion-pairing reverse-phase chromatography. An excellent linear relationship between ceftazidime peak height measurements and concentrations was demonstrated over the concentration range of 1-200 microg ml(-1). The advantage of this assay is the elimination of interference at the ceftazidime elution time that has been noted in previous studies and in our experience. Thus, this study describes an alternative, simple methodology that is clinically useful for analyzing ceftazidime in the research setting.

Prolonged opioid antagonism with naloxone in chronic renal failure.

Respiratory depression secondary to morphine intoxication occurred in an elderly patient with chronic renal failure (CRF). It was reversed with a continuous infusion of naloxone. Approximately 11 hours after the infusion was discontinued, the patient relapsed into respiratory depression consistent with opioid intoxication. He was rechallenged with a naloxone infusion with resolution of the opioid effects. This case suggests prolonged antagonism of opioid effects inconsistent with naloxones reported pharmacologic effects. Serum naloxone concentrations measured after the end of the infusion suggest that the drugs pharmacokinetics were significantly altered. Further research is necessary to characterize pharmacokinetic changes that occur in CRF. In the absence of this information, similar patients should be closely monitored for relapse of respiratory depression after naloxone is discontinued.