Early-onset Ventilator-associated Pneumonia Research Articles

Redefining Success for VAP: 360-Degree Approach

BACKGROUND: Ventilator-associated pneumonia (VAP) in hospital intensive care units (ICUs) is associated with high morbidity and mortality. Effective treatment of VAP can be challenging due to a high prevalence of Pseudomonas aeruginosa and multidrug-resistant (MDR) pathogens as causative organisms. OBJECTIVE: To present the etiology of VAP in the United States (including national resistance trends of common nosocomial pathogens) and review dosing strategies aimed to optimize pharmacokinetic-pharmacodynamic parameters of antimicrobial agents. SUMMARY: The majority of nosocomial pneumonia cases are caused by gram-negative pathogens, most commonly P. aeruginosa, Enterobacter spp., A. baumannii, and K. pneumoniae. S. aureus is the most common gram-positive pathogen, with 55% of VAP isolates exhibiting methicillin resistance. Combination therapy is recommended when MDR pathogens and P. aeruginosa are suspected, although short-course therapy and deescalation should be considered when appropriate to reduce the risk of resistance. Optimized dosing strategies are important in increasing the probability of achieving successful outcomes. For example, when administering intravenous β-lactam therapy, prolonged infusion can be effective in increasing the T > MIC. CONCLUSION: Clinicians need to be familiar with local antibiograms as well as regional resistance trends in order to choose appropriate therapy for VAP. Optimized dosing strategies can be effective in increasing the probability of attaining pharmacokinetic-pharmacodynamic targets predictive of successful clinical outcomes. J Manag Care Pharm. 2009;15(5)(Suppl):S5-S9 Copyright © 2009, Academy of Managed Care Pharmacy. All rights reserved. DAVID S. BURGESS, PharmD, FCCP, is Clinical Professor of Pharmacy and Medicine, University of Texas at Austin, Austin, Texas, and the University of Texas Health Science Center at San Antonio, San Antonio, Texas. CORRESPONDENCE: David S. Burgess, PharmD, FCCP, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MSC 6220, San Antonio, TX 78229-3900. Tel.: 210.567.8329; Fax: 210.567.8328; E-mail: burgessd@uthscsa.edu Author Introduction Ventilator-associated pneumonia (VAP) is among the most common nosocomial infections originating in the intensive care unit (ICU), affecting 9% to 27% of all intubated patients.1,2 The attributable mortality can be as high as 33% to 50%.1,2 The risk of VAP is correlated to the length of stay (LOS) in the hospital or ICU as well as to the duration of mechanical ventilation.2 Pseudomonas aeruginosa and multidrug-resistant (MDR) organisms account for over 20% of VAP infections, with higher rates observed in those with prolonged hospitalization.3 Infection by these problematic pathogens is associated with increased mortality, duration of mechanical ventilation, and hospital LOS.3 Therefore, when managing patients at high risk for VAP, it is important to recognize the local epidemiology and resistance trends in order to select the most appropriate initial antimicrobial therapy. Etiology of Hospital-Acquired Pneumonia Surveillance data from the National Healthcare Safety Network (NHSN, formerly the National Nosocomial Infections Surveillance System) have shown that gram-negative pathogens are the predominant cause of nosocomial pneumonia, accounting for approximately 70% of infections.4 Among the infections caused by gram-negative pathogens, P. aeruginosa is the leading cause (accounting for approximately 20%) followed by Enterobacter spp., Klebsiella pneumoniae, and Acinetobacter baumannii.4 The proportion of infections due to Acinetobacter has nearly doubled over the past 2 decades (from 4% in 1986 to 7% in 2003). However, there has been a gradual trend of increasing infections due to grampositive pathogens, mainly Staphylococcus aureus. The etiology of VAP can vary based on (a) local epidemiological trends as well as (b) the timing of onset of infection. According to the 2006–2007 NHSN data, the most common pathogen associated with VAP is S. aureus (24.4%) followed by P. aeruginosa (16.3%), Enterobacter spp. (8.4%), A. baumannii (8.4%), and K. pneumoniae (7.5%) (Table 1).5 The time of onset is also an important predictor of causative pathogens. Early-onset VAP, defined as VAP occurring within the first 5 days of hospitalization, is caused by enteric gram-negative bacteria (including Escherichia coli, K. pneumoniae, and Enterobacter spp.), Haemophilus influenzae, Streptococcus pneumoniae, and methicillin-susceptible S. aureus (MSSA).2,6 Late-onset VAP, defined as VAP occurring after 5 days of hospitalization, is more likely to be caused by MDR pathogens,2,6 including those associated with early-onset VAP as well as P. aeruginosa and A. baumannii. The variety and complexity of pathogens associated with VAP make choosing an appropriate initial therapy challenging. Appropriate Antimicrobial Therapy for VAP The American Thoracic Society (ATS) and the Infectious Diseases

Prevention and Diagnosis of Ventilator-Associated Pneumonia

Prevention and Diagnosis of Ventilator-Associated Pneumonia

Lavado broncoalveolar para el diagnóstico de neumonía en enfermos en ventilación mecánica

To evaluate the diagnostic role of bronchoalveolar lavage (BAL) in mechanically ventilated patients with suspected pneumonia and to describe the clinical outcome in the different kinds of pneumonia in critically ill patients.Descriptive study.A 17-bed medical and surgical intensive care unit.Mechanically ventilated patients admitted to the ICU from November 2003 to March 2006 with suspected pneumonia who underwent bronchoscopy with BAL.BAL was performed by fiberoptic bronchoscopy with three aliquots of 50 ml sterile normal saline. Recovered BAL fluid was pro-cessed for microbiologic analysis.Age, APACHE II score within the first 24 hours of admission, time on mechanical ventilation, ICU length of stay, mortality, and isolated bacteria were analyzed.A total of 96 cases of suspected pneumonia with BAL were recruited, including 4 groups: community associated pneumonia (CAP), 12 cases, early-onset ventilator-associated pneumonia (VAP), 26 cases, late-onset ventilator-associated pneumonia, 43 cases, and immunocompromised patients, 15 cases. BAL was positive (> 10000 ufc/ml) in 40 (41.7%) patients (2, 16, 17 and 5 patients with CAP, early-onset VAP, late-onset VAP and immunocompromised, respectively). Mortality was 33.3%, 26.9%, 25.6% and 73.3% in CAP, early-onset VAP, late-onset VAP and immunocompromised patients respectively.The low incidence of positive BAL in the CAP group supports using BAL only for particularly severe, selected cases. Mortality was very high in the immunocompromised patients. In the light of our personal experience, BAL is most useful in the diagnosis of pneumonia in the group of patients with VAP.

Efficacy and safety of doripenem versus piperacillin/tazobactam in nosocomial pneumonia: a randomized, open-label, multicenter study

ABSTRACTObjective: Doripenem is a new carbapenem that has broad-spectrum activity against bacterial pathogens commonly responsible for nosocomial pneumonia (NP). It has several advantages over currently available carbapenems and other classes of drugs used in this indication. This prospective, randomized, open-label, multicenter study was designed to establish whether doripenem was noninferior to piperacillin/tazobactam in NP.Methods: Adults (n = 448) with signs and symptoms of NP, including non-ventilated patients and those ventilated for <5 days, were stratified by ventilation mode, illness severity (Acute Physiology and Chronic Health Evaluation II score), and geographic region and then randomly allocated to treatment with doripenem 500 mg every 8 h by a 1-h intravenous (IV) infusion or piperacillin/tazobactam 4.5 g every 6 h by 30-min IV infusion. After receiving IV study drug for at least 72 h, eligible patients could be switched to oral levofloxacin 750 mg once daily. Antibiotic therapy was continued for a total of 7–14 days. The primary endpoint was the clinical cure rate, assessed 7–14 days after treatment completion, in clinically evaluable patients and in the clinical modified intent-to-treat population (cMITT).Results: Doripenem was noninferior to piperacillin/tazobactam. Clinical cure rates in clinically evaluable patients (n = 253) were 81.3% in the doripenem arm and 79.8% in the piperacillin/tazobactam arm (between-treatment difference: 1.5%; 95% confidence interval [CI], −9.1 to 12.1%) and in the cMITT population 69.5% and 64.1%, respectively, (between-treatment difference: 5.4%; 95% CI, −4.1 to 14.8%). Baseline resistance of Klebsiella pneumoniae and Pseudomonas aeruginosa to piperacillin/tazobactam was 44% and 26.9%, respectively; a doripenem minimum inhibitory concentration (MIC) >8 µg/mL occurred in 0% and 7.7%, respectively. Favorable microbiological outcome rates against Gram-negative pathogens were numerically higher with doripenem than with piperacillin/tazobactam, but the difference was not statistically significant. Both study drugs were generally well tolerated, as only 16.1% and 17.6% of patients receiving doripenem and piperacillin/tazobactam, respectively, had a drug-related adverse event. Study limitations included the open-label design, the low rate of monotherapy (adjunctive use of aminoglycoside was required when P. aeruginosa was suspected), and the exclusion of the most critically ill and immunocompromized patients.Conclusions: Doripenem was clinically and microbiologically effective in patents with NP, including those with early-onset ventilator-associated pneumonia, and was therapeutically noninferior to piperacillin/tazobactam.Trial registration: ClinicalTrials.gov identifier: NCT00211003.

Differences in Early- and Late-Onset Ventilator-Associated Pneumonia Between Surgical and Trauma Patients in a Combined Surgical or Trauma Intensive Care Unit

Ventilator-associated pneumonia (VAP) is a leading cause of morbidity in the perioperative period. Based on differences in causes, VAP has been divided into early (</=96 hours of admission) and late (>96 hours of admission) onset. We sought to compare differences in patient characteristics and outcome between early- and late-onset VAP in trauma and nontrauma surgical patients. A retrospective analysis of prospectively collected data were performed for all surgical and trauma patients admitted to the surgical or trauma intensive care unit of an academic medical center from December 1996 to March 2005 who developed VAP. Patients with early- and late-onset VAP were compared with regard to patient characteristics, cause, and outcome using bivariate and multivariate analyses. Three hundred thirty VAPs were identified in 233 trauma (71%) and 97 nontrauma surgery patients (29%). There was no statistically significant difference in recurrence, mortality, or length of stay between early- and late-onset VAP in trauma patients. Mortality for late- onset VAPs in nontrauma patients was 44% versus 23% for early-onset VAPs (p = 0.09). On a per case basis, trauma patients had significantly better mortality (11% vs. 41%) and length of stay (33.1 +/- 1.4 vs. 55.8 +/- 4.1 days) than nontrauma surgical patients with VAP (p < 0.0001), although the rate of VAP-related death favored the nontrauma patients (1.8 deaths of 100 intensive care unit trauma admissions vs. 1.1 deaths of 100 intensive care unit nontrauma admissions, p = 0.05). Although there is a trend toward worse outcome in nontrauma patients with late-onset VAP, trauma patients with late- and early-onset VAP behave similarly. On a per case basis, trauma patients have significantly better outcomes than nontrauma surgical patients with VAP when cared for within the same surgical or trauma intensive care unit.

Influence of an Endotracheal Tube with Polyurethane Cuff and Subglottic Secretion Drainage on Pneumonia

Subglottic secretion drainage (SSD) appears to be effective in preventing ventilator-associated pneumonia (VAP), primarily by reducing early-onset pneumonia; but it may not prevent late-onset pneumonia. We tested the hypothesis using an endotracheal tube incorporating an ultrathin polyurethane cuff (which reduces channel formation and fluid leakage from the subglottic area), in addition to an SSD lumen, which would reduce the incidence of late-onset VAP. To compare the incidence of VAP, using an endotracheal tube with polyurethane cuff and subglottic secretion drainage (ETT-PUC-SSD) versus a conventional endotracheal tube (ETT-C) with polyvinyl cuff, without subglottic secretion drainage. Clinical randomized trial in a 24-bed medical-surgical intensive care unit. Patients expected to require mechanical ventilation for more than 24 hours were randomly assigned to one of two groups: one was ventilated with ETT-PUC-SSD and the other with ETT-C. Tracheal aspirate samples were obtained during endotracheal intubation, then twice per week and finally on extubation. VAP was found in 31 of 140 (22.1%) patients in the ETT-C group and in 11 of 140 (7.9%) in the ETT-PUC-SSD group (P = 0.001). Cox regression analysis showed ETT-C as a risk factor for global VAP (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.66-6.67; P = 0.001), early-onset VAP (HR, 3.3; 95% CI, 1.19-9.09; P = 0.02), and late-onset VAP (HR, 3.5; 95% CI, 1.34-9.01; P = 0.01). The use of an endotracheal tube with polyurethane cuff and subglottic secretion drainage helps prevent early- and late-onset VAP. Clinical trial registered with www.clinicaltrials.gov (NCT 00475579).

Impact of a Protocol for Prevention of Ventilator-Associated Pneumonia

Several interventions have been shown to be effective in reducing the incidence of ventilator-associated pneumonia (VAP), but their implementation in clinical practice has not gained widespread acceptance. To determine the impact of a protocol that incorporates evidence-based interventions shown to reduce the frequency of VAP on the overall rate of VAP, early-onset VAP, and late-onset VAP in the intensive care unit (ICU) of a tertiary care adult teaching hospital. This pre- and postintervention observational study included mechanically ventilated patients admitted to the Montreal General Hospital ICU between November 2003 and May 2004 (preintervention) and between November 2004 and May 2005 (postintervention). A multidisciplinary prevention protocol was developed, implemented, and reinforced. Rates of VAP per 1000 ventilator-days were calculated pre- and postprotocol implementation for all patients, for patients with early-onset VAP, and for those with late-onset VAP. In the pre- and postintervention groups, 349 and 360 patients, respectively, were mechanically ventilated. Twenty-three VAP episodes occurred in 925 ventilator-days (crude incidence rate 25 per 1000) in the preintervention period. Following implementation, the VAP rate decreased to 22 episodes in 988 ventilator-days (crude incidence rate 22.3 per 1000), corresponding to a relative reduction in rate of 10.8% (p < 0.001). The incidence of early-onset VAP decreased from 31.0 to 18.5 VAP per 1000 ventilator-days (p < 0.001), while the incidence of late-onset VAP increased from 21.9 to 24.1 VAP per 1000 ventilator-days (p < 0.001). However, when all covariates were adjusted, the impact of the prevention protocol was not statistically significant. Implementation of a VAP prevention protocol incorporating evidence-based interventions reduced the crude incidence of VAP, early-onset VAP, and late-onset VAP. However, when covariates were adjusted, the beneficial effect was no longer observed. Further research is needed to assess the impact of such measures on VAP, early-onset VAP, and late-onset VAP.

Pneumonies acquises sous ventilation mécanique: suivez les recommandations!

To compare the clinical outcomes and the causative pathogens of early-onset and late-onset ventilator-associated pneumonia (VAP) diagnosed by bronchoalveolar lavage (BAL). Prospective, observational, epidemiological study. During a 7-years period, all first episodes of VAP were prospectively included. Diagnosis was confirmed by a BAL with a threshold of 10(4) cfu/ml. Late-onset pneumonia was defined if occurred after the seventh day after mechanical ventilation. One hundred and thirteen VAP were studied. Fifty were early-onsets and 63 late-onsets. Thirty-four per cent of early-onset VAP and 73% of late-onset VAP were due to potential multiresistants pathogens. Pseudomonas aeruginosa was the most commonly isolated bacteria both in early-onset and late-onset VAP (16 and 39% respectively). Morbidity and mortality (29 vs 29%, ns) were not statically different between the two groups (early-onset and late-onset VAP). In our study, both early-onset and late-onset VAP were mainly caused by potentially multiresistants bacteria, most commonly Gram negative bacilli. Even for early VAP, clinicians should be aware about all risk factors for potentially multiresistants pathogens and not only the delay of onset of the VAP episode.

Ventilator-Associated Pneumonia

Ventilator-Associated Pneumonia

Excess ICU mortality attributable to ventilator-associated pneumonia: The role of early vs late onset

To determine the impact of ventilator-associated pneumonia (VAP) on ICU mortality, and whether it is related to time of onset of pneumonia. Prospective cohort study. 16-bed medical-surgical ICU at a university-affiliated hospital. From 2002 to 2003, we recorded patients receiving mechanical ventilation for > 72 h. Patients developing an infection other than VAP were excluded. Patients definitively diagnosed with VAP (n=40) were cases and patients free of any infection acquired during ICU stay (n=61) were controls. The VAP-attributed mortality was defined as the difference between observed mortality and predicted mortality (SAPS II) on admission. Mechanical ventilation was longer in VAP patients (25 +/- 20 vs 11 +/- 9 days; p < 0.001), as was ICU stay (33 +/- 23 vs 14 +/- 12 days; p < 0.001). In the non-VAP group, no difference was found between observed and predicted mortality (27.9 vs 27.4%; p > 0.2). In the VAP group, observed mortality was 45% and predicted mortality 26.5% (p < 0.001), with attributable mortality 18.5%, and relative risk (RR) 1.7 (95% CI 1.12-23.17). No difference was observed between observed and predicted mortality in early-onset VAP (27.3 vs 25.8%; p > 0.20); in late-onset VAP, observed mortality was higher (51.7 vs 26.7%; p < 0.01) with attributable mortality of 25% and an RR 1.9 (95% CI 1.26-2.63). Empiric antibiotic treatment was appropriate in 77.5% of episodes. No differences in mortality were related to treatment appropriateness. In mechanically ventilated patients, VAP is associated with excess mortality, mostly restricted to late-onset VAP and despite appropriate antibiotic treatment.

Incidence of multidrug-resistant organisms causing ventilator-associated pneumonia in a tertiary care hospital: A nine months′ prospective study

BACKGROUND:Ventilator-associated pneumonia (VAP) is an important intensive care unit (ICU) infection in mechanically ventilated patients. VAP occurs approximately in 9-27% of all intubated patients. Due to the increasing incidence of multidrug-resistant organisms in ICUs, early and correct diagnosis of VAP is an urgent challenge for an optimal antibiotic treatment.AIM OF THE STUDY:The aim of the study was to assess the incidence of VAP caused by multidrug-resistant organisms in the multidisciplinary intensive care unit (MICU) of our tertiary care 1,400-bedded hospital.MATERIALS AND METHODS:This prospective study was done in the period from December 2005 to August 2006, enrolling patients undergoing mechanical ventilation (MV) for >48 h. Endotracheal aspirates (ETA) were collected from patients with suspected VAP, and quantitative cultures were performed on all samples. VAP was diagnosed by the growth of pathogenic organism ≥105 cfu/ml.RESULTS:Incidence of VAP was found to be 45.4% among the mechanically ventilated patients, out of which 47.7% had early-onset (<5 days MV) VAP and 52.3% had late-onset (>5 days MV) VAP. Multiresistant bacteria, mainly Acinetobacter spp. (47.9%) and Pseudomonas aeruginosa (27%), were the most commonly isolated pathogens in both types of VAP. Most of the isolates of Escherichia coli (80%) and Klebsiella pneumoniae (100%) produced extended-spectrum beta lactamases (ESBLs). As many as 30.43% isolates of Acinetobacter spp. showed production of AmpC beta lactamases among all types of isolates. Metallo-beta lactamases (MBLs) were produced by 50% of Pseudomonas aeruginosa and 21.74% of Acinetobacter spp.CONCLUSION:High incidence (45.4%) of VAP and the potential multidrug-resistant organisms are the real threat in our MICU. This study highlighted high incidence of VAP in our setup, emphasizing injudicious use of antimicrobial therapy. Combined approaches of rotational antibiotic therapy and education programs might be beneficial to fight against these MDR pathogens and will also help to decrease the incidence of VAP.

Treatment of ventilator-associated pneumonia with piperacillin-tazobactum and amikacin vs cefepime and levofloxacin: A randomized prospective study

Study Objectives: To compare the survival benefits and cost effectiveness of cefepime-levofloxacin (C-L) as an alternative empirical antibiotic therapy for ventilator associated pneumonia (VAP) with the most widely recommended combination of piperacillin-tazobactam and amikacin (P-T-A). Design: Prospective, observational, cohort study. Materials and Methods: A total number of 879 patients were admitted in the ICU during 1st April 2004 to 31 st March 2005 and were screened for the study. Ninety-three patients were clinically suspected to develop early onset VAP. The patients were randomly divided into two groups receiving Cefepime-Levofloxacin (C-L) or Piperacillin-Tazobactam-Amikacin (P-T-A) as empirical antibiotic therapy. Treatment outcome was compared between the groups, which included ICU mortality, duration of mechanical ventilation, duration of ICU stay and total cost incurred on antibiotics. Results: The epidemiological characteristics including mean age and APACHE II score were comparable between the two groups. The mortality rates in the two groups were similar. The duration of mechanical ventilation was shorter in C-L group (5-8 days) as compared to P-T-A group (6-11 days). Also, the mean duration of ICU stay was reduced in C-L group (16±2.1 days) as compared to P-T-A group (19±3.4 days). Further, the overall cost of antibiotics in C-L group was 1/3 rd of the cost in P-T-A group. Eleven patients were found to be receiving inappropriate antibiotics and seven patients developed ARF during the course of antibiotic therapy. These patients were excluded from the study. Conclusion: Cefepime-Levofloxacin combination is an effective alternative to piperacillin-tazobactam-amikacin for empirical treatment of VAP. It reduces the duration of mechanical ventilation, number of days of ICU stay and overall cost of antibiotics

Ertapenem in critically ill patients with early-onset ventilator-associated pneumonia: pharmacokinetics with special consideration of free-drug concentration

Most information about pharmacokinetics of antimicrobial agents is obtained from studies in healthy volunteers. However, antibiotics are therapeutically used in infected patients with very different pharmacokinetic properties compared with healthy individuals. In a single-centre, prospective, open-label study, 17 adult critically ill patients with early-onset ventilator-associated pneumonia (VAP) were treated with 1 g of ertapenem infusion once a day. Blood and urine samples were collected before and at different time-points up to 24 h after medication on day 1. Concentrations of ertapenem in plasma were determined with a validated HPLC method. Free-drug concentrations were estimated using a two-class binding site equation. The overall clinical success rate of the assessable cases was 66.7% (12/16). Pharmacokinetic parameters of ertapenem in our critically ill patients were clearly different when compared to those reported in the literature for healthy volunteers. The enhanced V(z) (17 vs. 8 L) and CL(TOT) (43 vs. 20 mL/min) with resulting lower C(max) (90 vs. 253 mg/L) and AUC(0-infinity) (418 vs. 817 mg x h/L) values were mainly related to hypoalbuminaemia (range 9.2-25.6 g/L) in our patient population. A population pharmacokinetic analysis using the NONMEM program indicated creatinine clearance as a significant covariate for explaining the between-subject variability of ertapenem in the patient population. Estimated free plasma concentrations of ertapenem exceeded a MIC(90) of 2 mg/L only for 6 h (25%) after infusion. For an adequate dose adjustment of highly protein-bound drugs like ertapenem, knowledge of actual albumin concentrations is necessary. A shortening of the dosage interval or continuous infusion of ertapenem should be considered to ensure optimal free concentrations in critically ill patients with severe hypoalbuminaemia and normal renal function.

Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator-associated pneumonia

We conducted a prospective, open-label study to determine the steady-state serum and epithelial lining fluid (ELF) concentrations of unbound ertapenem administered once daily to critically ill patients with early-onset ventilator-associated pneumonia (VAP). Prospective, open-label study in an intensive care unit and research ward in a university hospital. Fifteen patients with VAP received 1-h intravenous infusions of 1 g ertapenem once daily. After 2 days of therapy the steady-state serum and ELF concentrations of free ertapenem were determined by high-performance liquid chromatography. The median (interquartile range) free ertapenem peak (C(max)), intermediate (C(12)), and trough (C(min)) concentrations (mg/l) 1, 12, and 24 h after the end of infusion were 30.3 (27.1-37.8), 4.8 (3.9-6.4), and 0.8 (0.5-1.2) in serum and 9.4 (8.0-10.7), 2.0 (1.1-2.5), and 0.3 (0.2-0.4) in ELF, respectively, showing a median free ertapenem percentage penetration in ELF of approx. 30%. The median (interquartile range) serum area under concentration-time curve of free ertapenem during the observational period was 226.7 mg h(-1) l(-1) (202.2-263.9). Our study shows satisfactory results, with unbound ertapenem concentrations both in serum and ELF exceeding the MIC(90) values of most of the causative pathogens encountered in early-onset VAP during 50-100% time. This suggests that 1 g intravenous ertapenem administered once daily should be effective during the treatment of early-onset VAP in critically ill patients with no known risk factors for multidrug-resistant pathogens.

The clinical features of postoperative ventilator-associated pneumonia after lung surgery

To investigate the clinical features of postoperative ventilator-associated pneumonia (VAP) after lung surgery. Of 104 patients who had undergone lung surgery and been treated with ventilator in our surgical intensive care unit between January 2003 and March 2005, 35 patients met with the criteria of both VAP and postoperative pneumonia (POP), and 41 cases had no evidences of pneumonia. The clinical and laboratory data of all 76 cases were recorded and analyzed by a statistical software package (SPSS). The diagnosis of postoperative VAP was established clinically in 35 patients (46.1%), and etiologically in 33 cases. Compared to the patients without postoperative VAP, the patients with postoperative VAP had a significantly longer mean interval between intubation and operation [(2.7 +/- 2.9) days vs. (1.6 +/- 1.7) days, P = 0.039], a longer duration of mechanical ventilation [(32.2 +/- 37.7) days vs. (4.2 +/- 2.9) days, P < 0.001], and higher morbidity (20.0% vs. 2.4%, P = 0.013). There was a significant difference in mean duration of mechanical ventilation between the 15 cases of early-onset VAP and 20 cases of late-onset VAP (17 +/- 15 days vs. 43 +/- 46 days, P = 0.042). Among the initially detected pathogen, Staphylococcus aureus remains the most common Gram-positive coccus whereas Acinetobacter Baumannii took the place of Pseudomonas aeruginosa as the top Gram-negative rod. Postoperative VAP after lung surgery has different clinical features from VAP in medical ICU.

Gram-negative bacterial pneumonia: aetiology and management

Recent articles of clinical and investigational interest on Gram-negative pneumonia, particularly hospital-acquired and ventilator-associated pneumonia, are reviewed. The high rate of respiratory infections due to Gram-negative bacteria in late-onset ventilator-associated pneumonia has been repeatedly documented. The predominant pathogens are Pseudomonas aeruginosa and Acinetobacter baumannii. On the other hand, the frequency of Gram-negative bacteria in community-acquired pneumonia and in early-onset ventilator-associated pneumonia is increasing. Patients with risk factors for infection with resistant pathogens should initially receive a combination therapy that covers a broad spectrum, and, as soon as the pathogen and the susceptibilities are available, treatment should be simplified to a more targeted one (with the possible exception of P. aeruginosa pneumonia). Adequate dosing is of great importance and the use of pharmacodynamic/pharmacokinetic principles when prescribing antibiotics increases effectiveness. The optimal duration of therapy remains unknown; several studies have supported the use of shorter courses of treatment. Alternative treatment approaches (e.g. vaccines) are under investigation. The increasing frequency of resistant Gram-negative bacteria and the shortage of newer antibiotics in the pipeline with activity against Gram-negative bacteria is of concern. Early effective antimicrobial treatment is a key for the resolution of infection and improved survival.

Morbidity and cost burden of methicillin-resistant Staphylococcus aureus in early onset ventilator-associated pneumonia

IntroductionTo gain a better understanding of the clinical and economic outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in patients with early onset ventilator-associated pneumonia (VAP), we retrospectively analyzed a multihospital US database to identify patients with VAP over a 24 month period (2002–2003).MethodData recorded included physiologic, laboratory, culture, and other clinical variables from 59 institutions. VAP was defined as new positive respiratory culture after at least 24 hours of mechanical ventilation (MV) and the presence of primary or secondary ICD-9-CM diagnosis codes of pneumonia. Outcomes measures included in-hospital morbidity and mortality for the population overall and after onset of VAP (duration of MV, intensive care unit [ICU] stay, in-hospital stay, and case mix and severity-adjusted operating cost). The overall cost was calculated at the hospital level using the Center for Medicare and Medicaid Services Cost/Charge Index for each calendar year.ResultsA total of 499 patients were identified as having VAP. S. aureus was the leading organism (31% of isolates). Patients with MRSA were significantly older than patients with methicillin-sensitive Staphylococcus aureus (MSSA; median age 74 versus 67 years, P < 0.05) and more likely to be medical patients. Compared with MSSA patients, MRSA patients on average consumed excess resources of 4.4 (95% confidence interval 0.6–8.2) overall MV days, 3.8 (-0.5 to +8.0) days of inpatient length of stay (LOS), 5.3 (1.0–9.7) ICU days, and US$7731 (-US$8393 to +US$23,856) total cost after controlling for case mix and other factors. Furthermore, MRSA patients needed excess resources after the onset of VAP (4.5 [95% confidence interval 1.0–8.1] MV days, 3.7 [-0.5 to +8.0] inpatient days, and 4.4 [0.4–8.4] ICU days) after controlling for the same case mix and admission severity covariates.ConclusionS. aureus remains a common cause of VAP. VAP due to MRSA was associated with increased overall LOS, ICU LOS, and attributable ICU LOS compared with MSSA-related VAP. Although not statistically significant because of small sample size and large variation, the attributable excess costs of MRSA amounted to approximately US$8000 per case after controlling for case mix and severity.

Both early-onset and late-onset ventilator-associated pneumonia are caused mainly by potentially multiresistant bacteria

To compare the causative pathogens of early-onset and late-onset ventilator-associated pneumonia (VAP) diagnosed by bronchoalveolar lavage quantitative cultures. Most previous reports have been based on endotracheal aspirate cultures and gave uncertain findings. Prospective evaluation of consecutive patients with clinical suspicion for VAP. Multidisciplinary intensive care unit of a university hospital. During a 3-year period 473 patients with clinical suspicion of VAP entered the study. Diagnosis of VAP was confirmed by cultures of bronchoalveolar lavage (> 10(4) cfu/ml) specimens in 408 patients. Protected bronchoalveolar lavage samples were taken. Initial antibiotic therapy was modified upon bronchoalveolar lavage culture results. Among 408 patients 191 had early-onset (< 7 days mechanical ventilation) and 217 late-onset (> or = 7 days) VAP. Potentially multiresistant bacteria, mainly Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), were the most commonly isolated pathogens in both types of VAP. No difference was noted in the contribution of potentially multiresistant pathogens (79% vs. 85%), P. aeruginosa (42% vs. 47%), or MRSA (33% vs. 30%) between early-onset and late-onset VAP. Initial antibiotic therapy was modified in 58% of early-onset VAP episodes and in 36% of late-onset VAP episodes. No difference in mortality was found between the two types of VAP. Both early-onset and late-onset VAP were mainly caused by potentially multiresistant bacteria, most commonly P. aeruginosa and MRSA. Antimicrobial agents against these pathogens should be prescribed empirically, at least in our institution.

Antimicrobial treatment of lower respiratory tract infections in the hospital setting

Respiratory tract infections (RTIs) that may require hospitalization include acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP), which includes ventilator-associated pneumonia (VAP). Healthcare-associated pneumonia (HCAP) is treated similar to HAP and may be considered with HAP. For CAP requiring hospitalization, the current guidelines for the treatments of RTIs generally recommend either a beta-lactam and macrolide combination or a fluoroquinolone. The respiratory fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin) are excellent antibiotics due to high levels of susceptibility among gram-negative, gram-positive, and atypical pathogens. The fluoroquinolones are active against > 98% of Streptococcus pneumoniae, including penicillin-resistant strains. Fluoroquinolones are also recommended for AECB requiring hospitalization. Evidence from clinical trials suggests that levofloxacin monotherapy is as efficacious as combination ceftriaxone-erythromycin therapy in the treatment of patients hospitalized with CAP. For early-onset HAP, VAP, and HCAP without the risk of multidrug resistance, ceftriaxone, ampicillin-sulbactam, ertapenem, or one of the fluoroquinolones is recommended. High-dose, short-course therapy regimens may offer improved treatment due to higher drug concentrations, more rapid killing, increased adherence, and the potential to reduce development of resistance. Recent studies have shown that short-course therapy with levofloxacin, azithromycin, or telithromycin in patients with CAP was effective, safe, and tolerable and may control the rate of resistance.

Community-acquired bacteria frequently detected by means of quantitative polymerase chain reaction in nosocomial early-onset ventilator-associated pneumonia*

To test whether real-time polymerase chain reaction allows for rapid quantitative detection of Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila in bronchoalveolar lavage fluids and to determine the prevalence of these pathogens in nosocomial ventilator-associated pneumonia. Prospective epidemiologic study applying a new molecular biology-based diagnostic tool during a 27-month period. Three medical intensive care units of a tertiary care university hospital. One hundred patients suffering from nosocomial ventilator-associated pneumonia, hospitalized for > or =14 days, intubated for reasons other than pneumonia, and mechanically ventilated for >48 hrs. None. S. pneumoniae, M. pneumoniae, and C. pneumoniae were detected in bronchoalveolar lavage fluids of 100 patients in 20 (20%), three (3%), and two (2%) cases, respectively. There of 17 (71%) revealed no growth or no significant growth by conventional culture. In one patient, S. pneumoniae and M. pneumoniae were detected simultaneously. Corresponding colony-forming units/mL were partly up to 10 CFU/mL with Gram stainings showing signs of acute inflammation in 80%. A significant temporary correlation between the number of days on ventilator, development of nosocomial pneumonia, and the frequency of detection of these pathogens was found for day 4. S. pneumoniae, M. pneumoniae, and C. pneumoniae should be considered as causative agents in critically ill patients who develop early-onset nosocomial ventilator-associated pneumonia. Thus, empirical antimicrobial regimens should cover S. pneumoniae, Chlamydia, and Mycoplasma alike. Quantitative polymerase chain reaction is a fast diagnostic tool allowing for detection of these bacteria within 3 hrs in pretreated patients.