Moving towards real-time antimicrobial management of ventilator-associated pneumonia.
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Biomedical subjects
Publications and source records attributed to Marin H Kollef.
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The incidence of community-associated, healthcare-associated, and hospital-acquired sterile-site infections due to methicillin-resistant Staphylococcus aureus (MRSA) isolates and the susceptibility of the isolates to non- beta -lactam antibiotics were evaluated for 549 hospitalized patients during a 3-year period. The incidence of community-associated MRSA infection increased significantly. The annual percentage of MRSA isolates from cases of healthcare-associated and hospital-acquired infection that were susceptible to 3 or more non- beta -lactam antibiotics increased significantly.
Antibiotic resistance has emerged as an important determinant of mortality for patients in the intensive care unit (ICU) setting. This is largely due to the increasing presence of pathogenic microorganisms with resistance to existing antibiotic agents, resulting in the administration of inappropriate treatment. Escalating antibiotic resistance has also been associated with greater overall health care costs, as a result of prolonged hospitalizations and convalescence associated with failure of antibiotic treatment, the need to develop new antibiotic agents, and the implementation of broader infection control and public health interventions aimed at curbing the spread of antibiotic-resistant pathogens. Antibiotic cycling has been advocated as a tool to reduce the occurrence of antibiotic resistance, especially in the ICU setting. Unfortunately, the cumulative evidence to date suggests that antibiotic cycling has limited efficacy for preventing antibiotic resistance. Nevertheless, a strategy whereby multiple or all classes of antibiotics are available for use (i.e., antibiotic heterogeneity) can be part of a broader effort aimed at curtailing antibiotic resistance within ICUs. Such efforts should be routine, given the limited availability of new antibiotic drug classes for the foreseeable future.
INTRODUCTION: To 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). METHOD: Data 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. RESULTS: A 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 US7731 dollars (-US8393 dollars to +US23,856 dollars) 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. CONCLUSION: S. 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 US8000 dollars per case after controlling for case mix and severity.
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There is considerable evidence to suggest that specific interventions can be effectively employed to prevent hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). These interventions consist of pharmacological and nonpharmacological strategies that focus on prevention of aerodigestive tract colonization and the prevention of aspiration of contaminated secretions, the major pathogenetic mechanisms leading to HAP. Important components of effective preventive strategies focus on basic infection control principles like handwashing, adequate intensive care unit (ICU) staff education, and optimal resource utilization. Measures to prevent HAP/VAP extend into all aspects of daily intensive care practice, including antibiotic selection and duration of use, preferred routes of intubation, limitation of sedation, protocolized weaning, optimal use of noninvasive mask ventilation, patient positioning, ventilator circuit management, transfusion practices, nutritional support issues, stress ulcer prophylaxis, and glycemic control. Local programs encompassing these interventions should be applied at a multidisciplinary level, involve all caregivers, and include local surveillance programs for antibiotic-resistant bacteria. The importance of implementing preventive strategies is amplified by the anticipated limited availability of new antimicrobial drug classes for the foreseeable future. Effective implementation of these preventive principles can result in significant cost savings for society and reduce hospital mortality and morbidity for individual patients.
OBJECTIVE: To assemble the available clinical data on the prevention of antimicrobial resistance in the intensive care unit (ICU) setting. DATA SOURCE: A MEDLINE database search and references from identified articles were employed to obtain the literature relating to the prevention of antimicrobial resistance in the ICU. CONCLUSIONS: The ICU presents a unique environment for the conduct of clinical research. The closed physical space with centralized patient management and efficient data recovery allows important clinical questions to be evaluated in a timely manner. Antimicrobial resistance has emerged as an important determinant of mortality for patients in the ICU. Additionally, there is currently a limited pipeline of new agents for the treatment of emerging bacteria with new resistance genes that pose an increasing threat to the ICU patient. Effective strategies for the prevention of antimicrobial resistance within ICUs are available and should be implemented aggressively. These strategies can be divided into non-pharmacologic infection- control strategies (e.g., routine hand hygiene, infection-specific prevention protocols) and antibiotic management strategies (e.g., shorter courses of appropriate antibiotics, narrowing of the antimicrobial spectrum on the basis of culture results). Additional studies conducted in ICUs are needed urgently to identify the optimal approaches for the management of antibiotics in order to balance the need for efficacy with the ability to minimize resistance.
OBJECTIVE: To determine the impact of methicillin-resistant Staphylococcus aureus (MRSA) on length of stay in the intensive care unit (ICU) for patients with ventilator-associated pneumonia (VAP) and to control for the effect of initially inappropriate antibiotic treatment on outcomes by focusing only on persons who were given appropriate antibiotic therapy for their infection. DESIGN: Retrospective analysis of pooled, patient-level data from multiple clinical trials in VAP. SETTING: Multiple ICUs in France. SUBJECTS: Persons with bronchoscopically confirmed VAP due to either MRSA or methicillin-susceptible S. aureus (MSSA) and who received initially appropriate antibiotic treatment. All persons with MRSA VAP received vancomycin (15 mg/kg intravenously, twice daily). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared patients with MRSA VAP to persons with MSSA VAP. ICU length of stay represented the primary end point and ICU-free days served as a secondary end point. We recorded information regarding multiple confounders, including demographics, reasons for ICU admission and mechanical ventilation (MV), severity of illness at both ICU admission and time of diagnosis of VAP, and duration of mechanical ventilation before and following the onset of VAP. The final cohort included 107 patients, and one third of cases were due to MRSA. Despite receiving initially appropriate antibiotic treatment, median ICU length of stay was significantly longer for persons with MRSA infection (33 days vs. 22 days; p=.047). The median number of ICU-free days was concomitantly lower in MRSA VAP (0 days vs. 5 days; p=.011). Survival analysis employing a Cox proportional hazards model identified several predictors of remaining in the ICU: Pao2/Fio2 ratio at diagnosis of VAP, duration of MV before VAP, duration of MV after diagnosis of VAP, and reason for MV. Additionally, infection with MRSA as opposed MSSA doubled the probability of needing continued ICU care (hazard ratio, 2.08; 95% confidence interval, 1.09-3.95; p=.025). CONCLUSIONS: MRSA VAP independently prolongs the duration of ICU hospitalization, and in turn, increases overall costs, even for patients initially given appropriate antibiotic treatment. Confronting the adverse impact of MRSA will require efforts that address more than the initial antibiotic prescription.
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OBJECTIVES: To describe the frequency of pepsin-positive tracheal secretions (a proxy for the aspiration of gastric contents), outcomes associated with aspiration (including a positive Clinical Pulmonary Infection Score [a proxy for pneumonia] and use of hospital resources), and risk factors associated with aspiration and pneumonia in a population of critically ill tube-fed patients. DESIGN: Prospective descriptive study conducted over a 2-yr period. SETTING: Five intensive care units in a university-affiliated medical center with level I trauma status. PATIENTS: Each of the 360 adult patients participated for 4 days. Among the inclusion criteria were mechanical ventilation and tube feedings. An exclusion criterion was physician-diagnosed pneumonia at the time of enrollment. INTERVENTION: None. MEASUREMENTS AND MAJOR RESULTS: Almost 6,000 tracheal secretions collected during routine suctioning were assayed for pepsin; of these, 31.3% were positive. At least one aspiration event was identified in 88.9% (n = 320) of the participants. The incidence of pneumonia (as determined by the Clinical Pulmonary Infection Score) increased from 24% on day 1 to 48% on day 4. Patients with pneumonia on day 4 had a significantly higher percentage of pepsin-positive tracheal secretions than did those without pneumonia (42.2% vs. 21.1%, respectively; p < .001). Length of stay in the intensive care unit and need for ventilator support were significantly greater for patients with pneumonia (p < .01). A low backrest elevation was a risk factor for aspiration (p = .024) and pneumonia (p = .018). Other risk factors for aspiration included vomiting (p = .007), gastric feedings (p = .009), a Glasgow Coma Scale score <9 (p = .021), and gastroesophageal reflux disease (p = .033). The most significant independent risk factors for pneumonia were aspiration (p < .001), use of paralytic agents (p = .002), and a high sedation level (p = .039). CONCLUSIONS: Aspiration of gastric contents is common in critically ill tube-fed patients and is a major risk factor for pneumonia. Furthermore, it leads to greater use of hospital resources. Modifiable risk factors for aspiration need to be addressed.
OBJECTIVE: The first goal of this investigation was to determine the rate of appropriate initial antimicrobial administration to patients with methicillin-resistant Staphylococcus aureus (MRSA) sterile-site infections. Our second goal was to evaluate the influence of appropriate initial treatment of MRSA sterile-site infection on outcome. DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1200-bed urban teaching facility. PATIENTS: Adult patients requiring hospitalization identified to have an MRSA sterile-site infection. INTERVENTIONS: Retrospective data collection from automated hospital and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: Five hundred forty-nine patients with S. aureus sterile site infections were identified during a 3-yr period (January 2002 through December 2004). One hundred twenty-seven (23.1%) died during hospitalization. Hospital mortality was statistically greater for patients receiving inappropriate initial antimicrobial treatment (n = 380) within 24 hrs of a positive culture than for those receiving appropriate initial treatment (n = 169) (26.1% vs. 16.6%; p = .015). Multiple logistic regression analysis identified inappropriate initial antimicrobial treatment (adjusted odds ratio [AOR], 1.92; 95% confidence interval [CI], 1.48-2.50; p = .0134), vasopressor administration (AOR, 5.49; 95% CI, 4.08-7.38; p < .001), and increasing age (1-yr increments) (AOR, 1.03; 95% CI, 1.02-1.04; p < .001) as independent determinants of hospital mortality. CONCLUSIONS: Inappropriate initial antimicrobial treatment of MRSA sterile-site infections is common and is associated with an increased risk of hospital mortality. Appropriate antimicrobial treatment of MRSA sterile-site infections may be maximized by increased use of initial empirical antimicrobial treatment regimens targeting MRSA in patients at risk for this infection until organism identification and susceptibility become known.
OBJECTIVE: To gain a better understanding of the epidemiology, microbiology, and outcomes of early-onset, culture-positive, community-acquired, healthcare-associated, and hospital-acquired bloodstream infections. DESIGN: We analyzed a large U.S. database (Cardinal Health, MediQual, formerly MedisGroups) to identify patients with bacterial or fungal bloodstream isolates from 2002 to 2003. SETTING: The data set included administrative and clinical variables (physiologic, laboratory, culture, and other clinical) from 59 hospitals. Bloodstream infections were identified in those hospitals collecting clinical and culture data for at least the first 5 days of admission. PATIENTS: Patients with bloodstream infection within 2 days of admission were classified as having community-acquired bloodstream infection. Those with a prior hospitalization within 30 days, transfer from another facility, ongoing chemotherapy, or long-term hemodialysis were classified as having healthcare-associated bloodstream infection. Bloodstream infections that developed after day 2 of admission were classified as hospital-acquired bloodstream infection. A total of 6,697 patients were identified as having bloodstream infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Healthcare-associated bloodstream infection accounted for more than half (55.3%) of all bloodstream infections. Nearly two thirds (62.3%) of hospitalized patients with bloodstream infection suffered from either hospital-acquired bloodstream infection or healthcare-associated bloodstream infection and had higher morbidity and mortality rates than those with community-acquired bloodstream infection. Of all bloodstream infection pathogens, fungal organisms were associated with the highest crude mortality, longest length of stay in hospital, and greatest total charges. Of all bacterial bloodstream infections, methicillin-resistant Staphylococcus aureus was associated with the highest crude mortality rate (22.5%), the longest mean length of stay (11.1 +/- 10.7 days), and the highest median total charges ($36,109). After we controlled for confounding factors, methicillin-resistant S. aureus was associated with the highest independent mortality risk (odds ratio 2.70; confidence interval 2.03-3.58). S. aureus was the most commonly encountered pathogen in all types of early-onset bacteremia. CONCLUSIONS: Healthcare-associated bloodstream infection constitutes a distinct entity of bloodstream infection with its unique epidemiology, microbiology, and outcomes. Methicillin-resistant Staphylococcus aureus carries the highest relative mortality risk among all pathogens.
OBJECTIVE: To evaluate a standardized hospital order set for the management of septic shock in the emergency department. DESIGN: Before-after study design with prospective consecutive data collection. SETTING: Emergency department of a 1,200-bed academic medical center. PATIENTS: A total of 120 patients with septic shock. INTERVENTIONS: Implementation of a standardized hospital order set for the management of septic shock. MEASUREMENTS AND MAIN RESULTS: A total of 120 consecutive patients with septic shock were identified. Sixty patients (50.0%) were managed before the implementation of the standardized order set, constituting the before group, and 60 (50.0%) were evaluated after the implementation of the standardized order set, making up the after group. Demographic variables and severity of illness measured by the Acute Physiology and Chronic Health Evaluation II were similar for both groups. Patients in the after group received statistically more intravenous fluids while in the emergency department (2825 +/- 1624 mL vs. 3789 +/- 1730 mL, p = .002), were more likely to receive intravenous fluids of >20 mL/kg body weight before vasopressor administration (58.3% vs. 88.3%, p < .001), and were more likely to be treated with an appropriate initial antimicrobial regimen (71.7% vs. 86.7%, p = .043) compared with patients in the before group. Patients in the after group were less likely to require vasopressor administration at the time of transfer to the intensive care unit (100.0% vs. 71.7%, p < .001), had a shorter hospital length of stay (12.1 +/- 9.2 days vs. 8.9 +/- 7.2 days, p = .038), and a lower risk for 28-day mortality (48.3% vs. 30.0%, p = .040). CONCLUSIONS: Our study found that the implementation of a standardized order set for the management of septic shock in the emergency department was associated with statistically more rigorous fluid resuscitation of patients, greater administration of appropriate initial antibiotic treatment, and a lower 28-day mortality. These data suggest that the use of standardized order sets for the management of septic shock should be routinely employed.
PURPOSE OF REVIEW: The main goal of this review is to describe the emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a community pathogen. RECENT FINDINGS: Community-acquired MRSA has emerged as an important infection in the community setting. It has primarily been associated with skin and soft-tissue infections, but can also cause severe pulmonary infections, including pneumonia and empyema. Community-acquired MRSA is typically more susceptible to a wider class of antibiotics than healthcare-associated MRSA. Community-acquired MRSA is also more virulent compared with healthcare-associated MRSA isolates. Community-acquired MRSA usually contains the gene encoding Panton-Valentive leukocidin, which is a toxin that creates lytic pores in the cell membranes of neutrophils and induces the release of neutrophil chemotactic factors that promote inflammation and tissue destruction. The optimal antibiotic treatment for Panton-Valentive leukocidin-positive community-acquired MRSA is unknown; however, antibiotics with activity against MRSA and the ability to inhibit toxin production may be optimal (linezolid or clindamycin for susceptible isolates). SUMMARY: Clinicians should be aware of the emergence of community-acquired MRSA as an important cause of serious infections arising in the community setting. Appropriate antibiotic therapy should be initiated as soon as infection with this pathogen is suspected.
STUDY OBJECTIVES: To evaluate clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia (VAP), including the implementation of and outcomes associated with deescalation therapy. DESIGN: Prospective, observational, cohort study. SETTING: Twenty ICUs throughout the United States. PATIENTS: A total of 398 ICU patients meeting predefined criteria for suspected VAP. INTERVENTIONS: Prospective, handheld, computer-based data collection regarding routine VAP management according to local institutional practices, including clinical and microbiological characteristics, treatment patterns, and outcomes. MEASUREMENTS AND RESULTS: The most frequent ICU admission diagnoses in patients with VAP were postoperative care (15.6%), neurologic conditions (13.3%), sepsis (13.1%), and cardiac complications (10.8%). The mean (+/- SD) duration of mechanical ventilation prior to VAP diagnosis was 7.3 +/- 6.9 days. Major pathogens were identified in 197 patients (49.5%) through either tracheal aspirate or BAL fluid and included primarily methicillin-resistant Staphylococcus aureus (14.8%), Pseudomonas aeruginosa (14.3%), and other Staphylococcus species (8.8%). More than 100 different antibiotic regimens were prescribed as initial VAP treatment, the majority of which included cefepime (30.4%) or a ureidopenicillin/monobactam combination (27.9%). The mean duration of therapy was 11.8 +/- 5.9 days. In the majority of cases (61.6%), therapy was neither escalated nor deescalated. Escalation of therapy occurred in 15.3% of cases, and deescalation occurred in 22.1%. The overall mortality rate was 25.1%, with a mean time to death of 16.2 days (range, 0 to 49 days). The mortality rate was significantly lower among patients in whom therapy was deescalated (17.0%), compared with those experiencing therapy escalation (42.6%) and those in whom therapy was neither escalated nor deescalated (23.7%; chi2= 13.25; p = 0.001). CONCLUSIONS: Treatment patterns for VAP vary widely from institution to institution, and the overall mortality rate remains unacceptably high. The deescalation of therapy in VAP patients appears to be associated with a reduction in mortality, which is an association that warrants further clinical study.
OBJECTIVE: The goal of this investigation was to determine whether vancomycin pharmacokinetic indexes (eg, serum trough concentrations or area under the concentration curve [AUC] values) were associated with mortality for patients with health-care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching facility. PATIENTS: Adult patients requiring hospitalization who were identified as having HCAP attributed to MRSA by BAL semi-quantitative cultures. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: One hundred two patients with MRSA HCAP were identified over a 6.5-year period. Thirty-two patients (31.4%) died during their hospitalization. The mean (+/- SD) vancomycin trough concentrations (13.6 +/- 5.9 vs 13.9 +/- 6.7 microg/mL, respectively; p = 0.866) and AUC values (351 +/- 143 vs 354 +/- 109 microg/h/mL, respectively; p = 0.941) did not differ between survivors and nonsurvivors. The stratification of the vancomycin trough concentrations and AUC values yielded no relationship with hospital mortality. CONCLUSIONS: We found no evidence that greater vancomycin trough concentrations or AUC values correlated with hospital outcome. Based on these results, aggressive dosing strategies for vancomycin (eg, trough concentrations of > 15 microg/mL) may not offer any advantage over traditional dose targets (range, 5 to 15 microg/mL).
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