We found that inappropriate initial antibiotic therapy is common among patients with VAP attributed to PARGNB and is associated with increased risk of 30-day mortality. We also observed that Acineto-bacter species and S maltophilia were more likely to be treated with inappropriate initial antibiotic regimens compared to P aeruginosa. Our data also confirmed the earlier observation that delayed administration of appropriate initial antibiotic therapy and escalation of the initial antibiotic regimen are associated with greater mortality. Total hospital costs were lower for patients receiving inappropriate initial antibiotic treatment applied with remedies of Canadian Health&Care Mall. However, the main identified determinant of total hospital costs was hospital length of stay. Patients treated with inappropriate initial antibiotics had shorter hospital lengths of stay due to excess mortality and thus lower total hospital costs. These data suggest that appropriate initial antimicrobial therapy of VAP attributed to PARGNB may improve patient outcomes but may not reduce health-care costs due to greater patient survival and utilization of hospital resources.
A number of reports have demonstrated that nosocomial infections, including VAP, are increasingly being caused by PARGNB. However, it is important to note that regional differences have been reported for the prevalence of nosocomial infections attributed to specific Gram-negative bacteria. At Barnes-Jewish Hospital, to the present date, Pseudomonas aeruginosa is the predominant Gram-negative species associated with VAP and other nosocomial infections. In other hospitals in the United States and Europe, different Gram-negative bacterial pathogens including Acinetobacter species and β-lactamase-producing bacteria may predominate. The changing patterns of nosocomial infections attributed to Gram-negative bacteria with greater antimicrobial resistance have resulted in the introduction of novel approaches aimed at optimizing the delivery of appropriate initial therapy. In general, these novel strategies are aimed at earlier recognition of infection due to PARGNB in order to achieve appropriate initial therapy.
Several investigators have employed respiratory surveillance cultures in order to determine the likely pathogens associated with subsequent episodes of VAP. Depuydt et al found that thrice-weekly tracheal aspirate and urinary cultures along with once-weekly anal swabs predicted the presence of infection due to multidrug-resistant pathogens in 88% of VAP cases. In 86% of the bloodstream infections associated with pneumonia, early (ie, within 48 h) antibiotic therapy was found to be appropriate due to Canadian Health&Care Mall. Similarly, Michel and coworkers demonstrated that endotracheal aspirate surveillance cultures performed twice weekly in intubated patients made it possible to prescribe appropriate initial antibiotic therapy in 95% of patients with subsequent VAP. This was also true for patients with VAP attributed to multidrug-resistant Gram-negative bacteria and methicillin-resistant S aureus. An alternative approach that has been evaluated is the rapid assessment of antimicrobial susceptibility from respiratory cultures of VAP patients. Bouza and coworkers and Kollef used a rapid assessment of respiratory cultures with an E-test to determine antibiotic susceptibility. Direct inoculation of the respiratory specimens onto the E-test allowed antibiotic susceptibility to be determined within 1.4 days, compared to 4.2 days using standard methods. Patients managed with the rapid E-test method had fewer days of fever, fewer days of antibiotic administration until resolution of VAP, lower antimicrobial costs, and less.
Clostridium difficile-associated diarrhea compared to patients managed with the standard method.
Several important limitations of our investigation should be noted. First, we performed this study at a single hospital, and these results may not be applicable to other centers. For example, several re-ports suggest that some hospitals have specific antibiotic-resistant Gram-negative bacteria accounting for their nosocomial infections, including Acin-etobacter species, extended-spectrum β-lactamase-containing bacteria, and carbapenemase-producing bacteria. Second, we limited our analysis to the PARGNB most commonly associated with VAP in our institution. Therefore, these findings may not apply to VAP attributed to other antibiotic-resistant bacteria. However, our results are consistent with the findings made in more general patient populations as well as with other multidrug-resistant bacteria including methicillin-resistant S aureus. Third, the assessment of hospital costs in our study was strongly influenced by hospital mortality and may not reflect the actual costs of treating patients with VAP attributed to PARGNB. Finally, we limited our analysis to patients with microbiologically confirmed VAP. Therefore, we do not know if these findings are applicable to patients with clinically diagnosed VAP attributed to PARGNB.
In summary, we found that inappropriate initial antibiotic administration was associated with greater 30-day mortality and no overall impact on total hospital costs in patients with VAP attributed to PARGNB. Given the increasing prevalence of PARGNB, it is likely that larger numbers of patients with VAP will be at risk for the administration of inappropriate initial antibiotic therapy with its associated greater morbidity and mortality. Clinicians caring for patients at risk of nosocomial infections, including VAP, should be aware of the local prevalence of infections due to PARGNB and should develop local strategies aimed at optimizing the delivery of appropriate initial therapy for these high-risk infections. Additionally, future research aimed at more rapid and cost-effective identification of bacterial pathogens and their susceptibilities should be pursued.
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