Lymph node tuberculosis in patients from regions with varying burdens of tuberculosis and human immunodeficiency virus (HIV) inf
Clevenbergh, P. Maitrepierre, I. Simoneau, G. et al.
Presse Med. 2010 Jun 18.
BACKGROUND: Few large cohorts of patients with lymph node tuberculosis (LNTB) have been reported in developed countries. OBJECTIVE: To describe the epidemiological and clinical characteristics of LNTB in patients living in France but born and raised in geographic areas with varying burdens of tuberculosis and human immunodeficiency virus (HIV) infection. DESIGN: A retrospective study of all patients with bacteriologically-proven LNTB assessed in a French hospital from March 1996 through April 2005. RESULTS: The analysis included 92 patients. HIV coinfected patients had a higher risk than those without HIV of presenting with disseminated TB and systemic symptoms and of hospitalization. Lymph node diagnostic procedures had a high yield when samples were cultured. About 25% of patients had an abnormal chest radiograph, and most of them were positive for acid-fast bacilli on sputum smears or for Mycobacterium tuberculosis culture. Treatment was generally prescribed for a longer duration than that recommended by international guidelines. One quarter of the patients developed a paradoxical reaction. A high proportion of our patients were classified as nonadherent and 20% defaulted or were lost to follow-up. CONCLUSION: Most of the differences in the clinical presentation among patients from various geographic areas were driven by the epidemiology of TB and HIV in the countries of origin. LNTB is frequently a clinical sign of disseminated disease, and culture for M. tuberculosis from LN or other sites is crucial for diagnosis. Adopting the strategy of Directly Observed Treatment, Short course (DOTS) might reduce the rates of nonadherence and default. Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Decreasing ventilator-associated pneumonia in a trauma ICU.
Cocanour, C.S. Peninger, M. Domonoske, B.D. et al.
J Trauma. 2006 Jul;61(1):122-9; discussion 129-30.
BACKGROUND: The incidence of ventilator-associated pneumonia ranges from 10 to 25%, with mortality of 10 to 40%. It prolongs hospital stay and drives up hospital costs. Our Intensive Care Unit (ICU) ventilator-associated pneumonia (VAP) rates were hovering at the National Nosocomial Infection Surveillance (NNIS) 90th percentile (22.3-32.7 infections per 1,000 ventilator days from January 2002 through October 2002) necessitating a performance improvement initiative designed to decrease the incidence of VAP. METHODS: A ventilator bundle that incorporates the Center for Disease Control (CDC) Guidelines for Prevention of Nosocomial Pneumonia was instituted in June of 2002. In October 2002, an intervention that audited compliance with the ventilator bundle and provided real-time feedback to ICU staff was started. VAP rates were followed using NNIS criteria. Costs were evaluated using hospital TSI data. RESULTS: VAP did not decrease with institution of the ventilator bundle alone. However, VAP did significantly decrease when the compliance with the ventilator bundle was audited daily and weekly feedback was provided to the caregivers. From November 2002 through June 2003 VAP stayed between 0 and 12.8 per 1,000 ventilator days. The average cost of a VAP was 50,000 dollars. CONCLUSIONS: Prevention of VAP requires a concerted effort on the part of hospital administration, physicians, and ICU personnel. The program must be evidence-based, maintained, and accepted by ICU personnel. Continued education and feedback are crucial to maintaining a low VAP rate.
What is ventilator-associated pneumonia and why is it important?
Kollef, M.H.
Respir Care. 2005 Jun;50(6):714-21; discussion 721-4.
Hospital-associated pneumonia (HAP) is one of the most common infections acquired among hospitalized patients. HAP is associated with excess mortality and increased medical care costs. The rise in HAP due to antibiotic-resistant bacteria has resulted in more common administration of inappropriate antimicrobial treatment, with an associated increased risk of hospital mortality. Ventilator-associated pneumonia (VAP) refers to HAP occurring in patients requiring mechanical ventilation. VAP is the most common nosocomial infection among patients with acute respiratory failure. Physicians treating patients with HAP and VAP should be aware of the predominant local pathogens associated with these infections and their antimicrobial susceptibility patterns. This will allow more appropriate initial antibiotic selection in order to optimize treatment regimens and clinical outcomes. Additionally, clinical strategies aimed at the prevention of HAP and VAP should be employed in all hospital settings caring for patients at risk for these infections
Curbing resistance development: maximizing the utility of available agents.
Burgess, D.S.
J Manag Care Pharm. 2009 Jun;15(5 Suppl):S5-9.
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 -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.
Rational dosing of antimicrobial agents: pharmacokinetic and pharmacodynamic strategies.
Owens, R.C. Jr. Shorr, A.F.
Am J Health Syst Pharm. 2009 Jun 15;66(12 Suppl 4):S23-30.
PURPOSE: Using the principles of pharmacokinetic (PK) and pharmacodynamic (PD) dosing, the optimal dosing strategies of beta-lactams, macrolides, fluoroquinolones, and aminoglycosides for the treatment of community-acquired pneumonia (CAP) are reviewed. SUMMARY: The optimal dosing of antimicrobials according to PK and PD principles is one method to reduce the misuse and overuse of the agents and antimicrobial resistance. Based on PK/PD profiles, antimicrobial agents are divided into three groups: agents with concentration-dependent killing (e.g., fluoroquinolones, aminoglycosides), agents with time- dependent killing and minimal or no persistent effects (e.g., beta-lactams in most circumstances), and agents with time-dependent killing and moderate-to-prolonged persistent effects (e.g., azithromycin).(19) With concentration-dependent agents such as fluoroquinolones, it is the total amount of drug administered that determines efficacy. With time-dependent agents such as macrolides and beta-lactams, it is the duration of exposure to a specific minimum inhibitory concentration (MIC). That part is straight forward. When a concentration-dependent killing drug is able to achieve its optimal peak:MIC, peak:MIC becomes the determinant of efficacy. When such a drug cannot achieve its optimal peak:MIC, AUC:MIC should be used to determine efficacy. CONCLUSION: Optimizing the dose and duration of antimicrobial therapy via PK/PD principles is one strategy to reduce antimicrobial resistance. PK/PD-based dosing provides patient- and pathogen-specific therapy and have the potential to make antimicrobial therapy safer and more effective by accounting for factors such as renal function, underlying pathogen, and local patterns of resistance.
Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of dorip
Kollef, M.H. Nathwani, D. Merchant, S. et al.
Crit Care. 2010 May 10;14(3):R84.
ABSTRACT: INTRODUCTION: Ventilator-associated pneumonia (VAP) is associated with increased medical resource utilization, but few randomized studies have been conducted to evaluate the effect of initial antibiotic therapy. To assess medical resource utilization in patients with VAP, we conducted a pooled analysis of two prospective, randomized, open-label, multicenter, phase III studies, which also showed that doripenem was clinically noninferior to comparators. METHODS: We assessed durations of mechanical ventilation, intensive care unit (ICU) stay, and hospitalization in patients with VAP who received at least 1 dose of doripenem or a comparator in the phase III studies. Comparators were piperacillin/tazobactam (study 1) and imipenem (study 2). We analyzed between-group differences in medical resource utilization endpoints by comparison of Kaplan-Meier curves with generalized Wilcoxon test and in microbiologic eradication rates by two-sided Fisher's exact test. RESULTS: 625 patients with VAP were evaluated and received at least 1 dose of doripenem (n = 312) or a comparator (n = 313). Median durations of mechanical ventilation (7 versus 10 days; P = 0.008) and hospitalization (22 versus 26 days; P = 0.010) were shorter for doripenem than comparators; corresponding ICU stays were 12 and 13 days (P = 0.065). All-cause, overall mortality rates were similar (51/312 [16%] versus 47/313 [15%]; P = 0.648). MIC90 values against Pseudomonas aeruginosa for doripenem versus imipenem were 4 versus 16 mug/mL in study 2. P. aeruginosa was eradicated from 16/24 (67%) doripenem recipients and 10/24 (42%) comparator recipients (P = 0.147). In patients with P. aeruginosa at baseline, median durations of mechanical ventilation (7 versus 13 days; P = 0.031) and ICU stay (13 versus 21 days; P = 0.027) were shorter for doripenem; corresponding hospital stays were 24 and 35 days (P = 0.129). CONCLUSIONS: Doripenem was associated with lower medical resource utilization than comparators. Differences in antipseudomonal activity may have contributed to these findings. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00211003 (study 1) and NCT00211016 (study 2).
Multidrug resistance among gram-negative pathogens that caused healthcare-associated infections reported to the National Healthc
Kallen, A.J. Hidron, A.I. Patel, J. et al.
Infect Control Hosp Epidemiol. 2010 May;31(5):528-31.
We evaluated isolates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii that were reported to the National Healthcare Safety Network from January 2006 through December 2008 to determine the proportion that represented multidrug-resistant phenotypes. The pooled mean percentage of resistance varied by the definition used; however, multidrug resistance was relatively common and widespread.
The current state of multidrug-resistant gram-negative bacilli in North America.
Nicasio, A.M. Kuti, J.L. Nicolau, D.P.
Pharmacotherapy. 2008 Feb;28(2):235-49.
Although much of today's media focuses on multidrug-resistant gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, resistance within gram-negative bacilli continues to rise, occasionally creating situations in which few or no antibiotics that retain activity are available. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella sp are emerging threats nationally. Although carbapenems are considered the antibiotic class of choice to treat ESBL-producing Enterobacteriaceae, the ability of these organisms to produce carbapenemases has now become apparent in some regions throughout the United States. Although still rare, Klebsiella sp that produce KPC-2 retain susceptibility only to tigecycline, polymyxins, and occasionally aminoglycosides. Multidrug resistance among Pseudomonas aeruginosa and Acinetobacter sp has always been apparent across many hospitals in the United States. Recent surveillance indicates increasing resistance to all currently available antibiotics, including carbapenems, cephalosporins, penicillins, fluoroquinolones, and aminoglycosides. Against many strains, only polymyxins retain activity; however, resistance has also been reported to these agents. Fortunately, resistance mechanisms such as metallo-beta-lactamases are still rare in the United States. As no new antibiotics with novel mechanisms against many of these gram-negative bacilli are expected to be developed in the foreseeable future, careful and conservative use of agents combined with good infection control practices is required.
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