Beyond Infection: Mortality and End-of-Life Care Associated with Infectious Disease Consultation in an Academic Health System.

BACKGROUND: Infectious diseases (ID) physicians are increasingly faced with the challenge of caring for patients with terminal illnesses or incurable infections. METHODS: This was a retrospective cohort of all patients with an ID consult within an academic health system 1/1/2014 - 12/31/2023, including community, general, and transplant ID consult services. RESULTS: There were 60,820 inpatient ID consults (17,235 community, 29,999 general, and 13,586 transplant) involving 37,848 unique patients. The number of consults increased by 94% and the rate rose from 5.0 to 9.9 consults per 100 inpatients (p<0.001). In total, 7.5% of patients receiving an ID consult died during admission, and 1,006 (2.6%) of patients were discharged to hospice. In-hospital mortality was 5.2% for community ID, 7.8% for general ID, and 10.7% for transplant ID patients (p<0.001). Six-month mortality was 9% for all non-obstetric admissions, , vs. 19% for community ID, 20.9% for general ID, and 22.3% for transplant ID.In total 2,866 (7.6%) of all patients receiving ID consultation also received palliative care consultation during the same hospitalization. The index ID consult preceded any palliative consult in the majority (69.5%) of cases. 16.3% of patients had a do-not-resuscitate order during the index hospitalization. 12.2% of all patients with a do-not-resuscitate order had this placed on the same day as the ID consult. CONCLUSIONS: Patients receiving ID consultation were increasingly complex and more likely to die soon after consultation. These results provide a framework for ID clinicians to consider their role in end-of-life care.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

Social Disadvantage, Politics, and Severe Acute Respiratory Syndrome Coronavirus 2 Trends: A County-level Analysis of United States Data.

BACKGROUND: Understanding the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for public health control efforts. Social, demographic, and political characteristics at the United States (US) county level might be associated with changes in SARS-CoV-2 case incidence. METHODS: We conducted a retrospective analysis of the relationship between the change in reported SARS-CoV-2 case counts at the US county level during 1 June-30 June 2020 and social, demographic, and political characteristics of the county. RESULTS: Of 3142 US counties, 1023 were included in the analysis: 678 (66.3%) had increasing and 345 (33.7%) nonincreasing SARS-CoV-2 case counts between 1 June and 30 June 2020. In bivariate analysis, counties with increasing case counts had a significantly higher Social Deprivation Index (median, 48 [interquartile range {IQR}, 24-72]) than counties with nonincreasing case counts (median, 40 [IQR, 19-66]; P = .009). Counties with increasing case counts were significantly more likely to be metropolitan areas of 250 000-1 million population (P < .001), to have a higher percentage of black residents (9% vs 6%; P = .013), and to have voted for the Republican presidential candidate in 2016 by a ≥10-point margin (P = .044). In the multivariable model, metropolitan areas of 250 000-1 million population, higher percentage of black residents, and a ≥10-point Republican victory were independently associated with increasing case counts. CONCLUSIONS: Increasing case counts of SARS-CoV-2 in the US during June 2020 were associated with a combination of sociodemographic and political factors. Addressing social disadvantage and differential belief systems that may correspond with political alignment will play a critical role in pandemic control.

In pursuit of the holy grail: Improving C. difficile testing appropriateness with iterative electronic health record clinical decision support and targeted test restriction.

OBJECTIVE: To determine the impact of electronic health record (EHR)-based interventions and test restriction on Clostridioides difficile tests (CDTs) and hospital-onset C. difficile infection (HO-CDI). DESIGN: Quasi-experimental study in 3 hospitals. SETTING: 957-bed academic (hospital A), 354-bed (hospital B), and 175-bed (hospital C) academic-affiliated community hospitals. INTERVENTIONS: Three EHR-based interventions were sequentially implemented: (1) alert when ordering a CDT if laxatives administered within 24 hours (January 2018); (2) cancellation of CDT orders after 24 hours (October 2018); (3) contextual rule-driven order questions requiring justification when laxative administered or lack of EHR documentation of diarrhea (July 2019). In February 2019, hospital C implemented a gatekeeper intervention requiring approval for all CDTs after hospital day 3. The impact of the interventions on C. difficile testing and HO-CDI rates was estimated using an interrupted time-series analysis. RESULTS: C. difficile testing was already declining in the preintervention period (annual change in incidence rate [IR], 0.79; 95% CI, 0.72-0.87) and did not decrease further with the EHR interventions. The laxative alert was temporally associated with a trend reduction in HO-CDI (annual change in IR from baseline, 0.85; 95% CI, 0.75-0.96) at hospitals A and B. The gatekeeper intervention at hospital C was associated with level (IRR, 0.50; 95% CI, 0.42-0.60) and trend reductions in C. difficile testing (annual change in IR, 0.91; 95% CI, 0.85-0.98) and level (IRR 0.42; 95% CI, 0.22-0.81) and trend reductions in HO-CDI (annual change in IR, 0.68; 95% CI, 0.50-0.92) relative to the baseline period. CONCLUSIONS: Test restriction was more effective than EHR-based clinical decision support to reduce C. difficile testing in our 3-hospital system.

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING: National Institute of Allergy and Infectious Diseases.

Early surgery in patients with infective endocarditis: a propensity score analysis.

BACKGROUND: An accurate assessment of the predictors of long-term mortality in patients with infective endocarditis is not possible using retrospective data because of inherent treatment biases and predictable imbalances in the distribution of prognostic factors. Largely because of these limitations, the role of surgery in long-term survival has not been adequately studied. METHODS: Data were collected prospectively from 426 patients with infective endocarditis. Variables associated with surgery in patients who did not have intracardiac devices who had left-side-associated valvular infections were determined using multivariable analysis. Propensity scores were then assigned to each patient based on the likelihood of undergoing surgery. Using individual propensity scores, 51 patients who received medical and surgical treatment were matched with 51 patients who received medical treatment only. RESULTS: The following factors were statistically associated with surgical therapy: age, transfer from an outside hospital, evidence of infective endocarditis on physical examination, the presence of infection with staphylococci, congestive heart failure, intracardiac abscess, and undergoing hemodialysis without a chronic catheter. After adjusting for surgical selection bias by propensity score matching, regression analysis of the matched cohorts revealed that surgery was associated with decreased mortality (hazard ratio, 0.27; 95% confidence interval, 0.13-0.55). A history of diabetes mellitus (hazard ratio, 4.81; 95% confidence interval, 2.41-9.62), the presence of chronic intravenous catheters at the beginning of the episode (hazard ratio, 2.65; 95% confidence interval, 1.31-5.33), and paravalvular complications (hazard ratio, 2.16; 95% confidence interval, 1.06-4.44) were independently associated with increased mortality. CONCLUSIONS: Differences between clinical characteristics of patients with infective endocarditis who receive medical therapy versus patients who receive surgical and medical therapy are paramount. After controlling for inherent treatment selection bias and imbalances in prognostic factors using propensity score methodology, risk factors associated with increased long-term mortality included diabetes mellitus, the presence of a chronic catheter at the onset of infection, and paravalvular complications. In contrast, surgical therapy was associated with a significant long-term survival benefit.

Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia.

BACKGROUND: Because of its ease of dosing, vancomycin is commonly used to treat methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in patients undergoing long-term hemodialysis. Clinical outcomes resulting from such a therapeutic strategy have not been well defined. METHODS: We prospectively identified patients undergoing long-term hemodialysis who received a diagnosis of MSSA bacteremia. Clinical outcomes were grouped according to the predominant antibiotic received during their therapy (vancomycin or a first-generation cephalosporin [cefazolin]). Treatment failure (defined as death or recurrent infection) was determined at 12 weeks after the initial positive blood culture results. A multivariable analysis was used to adjust for confounders. RESULTS: During an 84-month period, 123 hemodialysis-dependent patients with MSSA bacteremia were identified. Patients receiving vancomycin (n=77) tended to be younger (51 vs. 57 years; P=.06) and had a lower rates of metastatic complications at presentation (11.7% vs. 36.7%; P=.001) than did those receiving cefazolin (n=46). The 2 groups were similar with regard to Acute Physiology and Chronic Health Evaluation II scores, comorbidities, source of infection, type of hemodialysis access, and access removal rates. Treatment failure was more common among patients receiving vancomycin (31.2% vs. 13%; P=.02). In the multivariable analysis, factors independently associated with treatment failure included vancomycin use (odds ratio, 3.53; 95% confidence interval, 1.15-13.45) and retention of the hemodialysis access (odds ratio, 4.99; 95% confidence interval, 1.89-13.76). CONCLUSIONS: Hemodialysis-dependent patients with MSSA bacteremia treated with vancomycin are at a higher risk of experiencing treatment failure than are those receiving cefazolin. In the absence of patient specific circumstances (e.g., allergy to beta-lactams), vancomycin should not be continued beyond empirical therapy for hemodialysis-dependent patients with MSSA bacteremia.

Methicillin-resistant Staphylococcus aureus outbreak in an intensive care nursery: potential for interinstitutional spread.

BACKGROUND: After surveillance surveys documented the absence of methicillin-resistant Staphylococcus aureus (MRSA) in our intensive care nursery, an outbreak of MRSA infection occurred there during a 7-month period in 2005. METHODS: Control measures included reinforcement of hand hygiene and contact precautions procedures. Active surveillance cultures were obtained on all neonates, including interinstitutional transfers. A cohort unit was dedicated exclusively for neonates with MRSA. Pulsed-field gel electrophoresis was performed on isolates to determine relatedness. We surveyed transferring hospitals to evaluate MRSA activity and surveillance practices in their nurseries. RESULTS: Twenty-five neonates were colonized with MRSA; 9 of these had clinical infections. Isolates from 18 of 21 neonates from this outbreak and 4 neonates from a previous cluster were identical, including 1 isolate obtained upon transfer from another institution. Admission and discharge logs from a 9-month period showed that 127 of 460 admissions (27.6%) were admitted from 34 hospitals, and 247 of 460 (53.7%) were discharged to 32 hospitals. Among 30 transferring hospitals responding to our survey, MRSA activity occurred in 2 of 28 (7%) level 1 nurseries, 4 of 11 (36%) level 2 nurseries and 6 of 10 (60%) level 3 nurseries. Nine of the 30 hospitals (30%) performed some active surveillance. CONCLUSIONS: Interinstitutional transfer can play a role in the initiation and propagation of MRSA outbreaks in neonatal nurseries. The burden of MRSA in area nurseries and the rate of transfers affect the potential for interhospital spread of MRSA and may justify changes in policy regarding surveillance for MRSA and communication between hospitals.

Favorable impact of an infection control network on nosocomial infection rates in community hospitals.

OBJECTIVE: To describe an infection control network (the Duke Infection Control Outreach Network [DICON]) and its impact on nosocomial infection rates in community hospitals. DESIGN: Prospective cohort study of rates of nosocomial infections and exposures of employees to bloodborne pathogens in hospitals during the first 3 years of their affiliation with DICON. Attributable cost and mortality estimates were obtained from published studies.Setting. Twelve community hospitals in North Carolina and Virginia. RESULTS: During the first 3 years of hospital affiliation with DICON, annual rates of nosocomial bloodstream infections at study hospitals decreased by 23% (P = .009). Annual rates of nosocomial infection and colonization due to methicillin-resistant Staphylococcus aureus decreased by 22% (P = .002), and rates of ventilator-associated pneumonia decreased by 40% (P = .001). Rates of exposure of employees to bloodborne pathogens decreased by 18% (P = .003). CONCLUSIONS: The establishment of an infection control network within a group of community hospitals was associated with substantial decreases in nosocomial infection rates. Standard surveillance methods, frequent data analysis and feedback, and interventions based on guidelines and protocols from the Centers for Disease Control and Prevention were the principal strategies used to achieve these reductions. In addition to lessening the adverse clinical outcomes due to nosocomial infections, these reductions substantially decreased the economic burden of infection: the decline in nosocomial bloodstream infections and ventilator-associated pneumonia alone yielded potential savings of 578,307 US dollars to 2,195,954 US dollars per year at the study hospitals.

Clinical outcomes and costs due to Staphylococcus aureus bacteremia among patients receiving long-term hemodialysis.

OBJECTIVE: To examine the clinical outcomes and costs associated with Staphylococcus aureus bacteremia among hemodialysis-dependent patients. DESIGN: Prospectively identified cohort study. SETTING: A tertiary-care university medical center in North Carolina. PATIENTS: Two hundred ten hemodialysis-dependent adults with end-stage renal disease hospitalized with S. aureus bacteremia. RESULTS: The majority of the patients (117; 55.7%) underwent dialysis via tunneled catheters, and 29.5% (62) underwent dialysis via synthetic arteriovenous fistulas. Vascular access was the suspected source of bacteremia in 185 patients (88.1%). Complications occurred in 31.0% (65), and the overall 12-week mortality rate was 19.0% (40). The mean cost of treating S. aureus bacteremia, including readmissions and outpatient costs, was $24,034 per episode. The mean initial hospitalization cost was significantly greater for patients with complicated versus uncomplicated S. aureus bacteremia ($32,462 vs $17,011; P = .002). CONCLUSION: Interventions to decrease the rate of S. aureus bacteremia are needed in this high-risk, hemodialysis-dependent population.

Costs and outcomes among hemodialysis-dependent patients with methicillin-resistant or methicillin-susceptible Staphylococcus aureus bacteremia.

OBJECTIVE: Comorbid conditions have complicated previous analyses of the consequences of methicillin resistance for costs and outcomes of Staphylococcus aureus bacteremia. We compared costs and outcomes of methicillin resistance in patients with S. aureus bacteremia and a single chronic condition. DESIGN, SETTING, AND PATIENTS: We conducted a prospective cohort study of hemodialysis-dependent patients with end-stage renal disease and S. aureus bacteremia hospitalized between July 1996 and August 2001. We used propensity scores to reduce bias when comparing patients with methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus bacteremia. Outcome measures were resource use, direct medical costs, and clinical outcomes at 12 weeks after initial hospitalization. RESULTS: Fifty-four patients (37.8%) had MRSA and 89 patients (62.2%) had MSSA. Compared with patients with MSSA bacteremia, patients with MRSA bacteremia were more likely to have acquired the infection while hospitalized for another condition (27.8% vs 12.4%; P = .02). To attribute all inpatient costs to S. aureus bacteremia, we limited the analysis to 105 patients admitted for suspected S. aureus bacteremia from a community setting. Adjusted costs were higher for MRSA bacteremia for the initial hospitalization (21,251 dollars vs 13,978 dollars; P = .012) and after 12 weeks (25,518 dollars vs 17,354 dollars; P = .015). At 12 weeks, patients with MRSA bacteremia were more likely to die (adjusted odds ratio, 5.4; 95% confidence interval, 1.5 to 18.7) than were patients with MSSA bacteremia. CONCLUSIONS: Community-dwelling, hemodialysis-dependent patients hospitalized with MRSA bacteremia face a higher mortality risk, longer hospital stays, and higher inpatient costs than do patients with MSSA bacteremia.

Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection.

Data for 479 patients were analyzed to assess the impact of methicillin resistance on the outcomes of patients with Staphylococcus aureus surgical site infections (SSIs). Patients infected with methicillin-resistant S. aureus (MRSA) had a greater 90-day mortality rate than did patients infected with methicillin-susceptible S. aureus (MSSA; adjusted odds ratio, 3.4; 95% confidence interval, 1.5-7.2). Patients infected with MRSA had a greater duration of hospitalization after infection (median additional days, 5; P<.001), although this was not significant on multivariate analysis (P=.11). Median hospital charges were 29,455 dollars for control subjects, 52,791 dollars for patients with MSSA SSI, and 92,363 dollars for patients with MRSA SSI (P<.001 for all group comparisons). Patients with MRSA SSI had a 1.19-fold increase in hospital charges (P=.03) and had mean attributable excess charges of 13,901 dollars per SSI compared with patients who had MSSA SSIs. Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI.

Surgical-site infection due to Staphylococcus aureus among elderly patients: mortality, duration of hospitalization, and cost.

OBJECTIVES: To examine the impact of surgical-site infection (SSI) due to Staphylococcus aureus on mortality, duration of hospitalization, and hospital charges among elderly surgical patients and the impact of older age on these outcomes by comparing older and younger patients with S. aureus SSI. DESIGN: A nested cohort study. SETTING: A 750-bed, tertiary-care hospital and a 350-bed community hospital. PATIENTS: Ninety-six elderly patients (70 years and older) with S. aureus SSI were compared with 2 reference groups: 59 uninfected elderly patients and 131 younger patients with S. aureus SSI. RESULTS: Compared with uninfected elderly patients, elderly patients with S. aureus SSI were at risk for increased mortality (odds ratio [OR], 5.4; 95% confidence interval [CI95], 1.5-20.1), postoperative hospital-days (2.5-fold increase; CI95, 2.0-3.1), and hospital charges (2.0-fold increase; CI95, 1.7-2.4; dollar 41,117 mean attributable charges per SSI). Compared with younger patients with S. aureus SSI, elderly patients had increased mortality (adjusted OR, 2.9; CI95, 1.1-7.6), hospital-days (9 vs 13 days; P = .001), and median hospital charges (dollar 45,767 vs dollar 85,648; P < .001). CONCLUSIONS: Among elderly surgical patients, S. aureus SSI was independently associated with increased mortality, hospital-days, and cost. In addition, being at least 70 years old was a predictor of death in patients with S. aureus SSI.

Control of nosocomial acquisition of vancomycin-resistant Enterococcus through active surveillance of hemodialysis patients.

Hemodialysis-dependent patients are an important VRE source. After implementation of active surveillance for VRE targeting hemodialysis patients, the hospital-wide nosocomial VRE rate increased by 41%, but decreased by 41% among non-hemodialysis patients (P = .05). To assess the effectiveness of active surveillance, patients undergoing active surveillance should be analyzed separately from other patients.

Pathogens resistant to antimicrobial agents: epidemiology, molecular mechanisms, and clinical management.

Resistance to antimicrobial drugs is increasing at an alarming rate among both gram-positive and gram-negative bacteria. Traditionally, bacteria resistant to multiple antimicrobial agents have been restricted to the nosocomial environment. A disturbing trend has been the recent emergence and spread of resistant pathogens and resistance traits in nursing homes, the community, as well as in hospitals. This article reviews the epidemiology, molecular mechanisms of resistance, and treatment options for pathogens resistant to antimicrobial drugs.

Therapeutic drug monitoring of antimycobacterial drugs in patients with both tuberculosis and advanced human immunodeficiency virus infection.

STUDY OBJECTIVE: To determine the feasibility of therapeutic drug monitoring for adjusting low serum antimycobacterial concentrations in patients with both tuberculosis and advanced human immunodeficiency virus (HIV). DESIGN: Retrospective cohort study. DATA SOURCE: De-identified dataset from a tuberculosis clinic. PATIENTS: Twenty-one patients (median age 38 yrs, range 25-68 yrs) with advanced HIV infection (CD4(+) cell count < 100 cells/mm(3)) who received treatment for active tuberculosis between March 2002 and September 2007. MEASUREMENTS AND MAIN RESULTS: We evaluated data based on the practices performed at the tuberculosis clinic. After the daily doses of isoniazid and rifamycins (rifampin or rifabutin) were ingested, serum concentrations were obtained at 2 hours for isoniazid and rifampin, at 3 hours for rifabutin, and, when possible, at 6 hours for all three drugs to detect delayed absorption. Antimycobacterial drug concentrations were compared with published reference levels, and dosages were adjusted to achieve desired concentrations. Costs of monitoring were recorded for all patients. Of the 21 patients, 18 (86%) had low serum concentrations of at least one drug 2 hours after ingestion: 2 (10%) had low isoniazid concentrations, 5 (24%) had low rifamycin concentrations, and 11 (52%) had low serum concentrations of both drugs. The median number of dosage adjustments to attain normal concentrations was 1 (range 0-4 adjustments). The median cost/patient for therapeutic drug monitoring was $619 (range $230-1948). The median final doses to achieve normal concentrations were isoniazid 600 mg/day (range 300-1500 mg/day), rifampin 1050 mg/day (range 600-1200 mg/day), and rifabutin 300 mg (range 150-450 mg) 3 times/week. No patient demonstrated any adverse effects attributed to these higher doses. CONCLUSION: Low serum concentrations of antituberculous drugs, which suggest malabsorption, are common among patients with advanced HIV who also have tuberculosis but can be overcome with higher doses. Therapeutic drug monitoring may be an effective tool to optimize therapy, but needs further study.

Mortality and time to extubation in severe hospital-acquired pneumonia.

BACKGROUND: This study examined predictors of in-hospital mortality and time to extubation among patients with acute, severe hospital-acquired pneumonia (HAP) managed in the intensive care unit (ICU). METHODS: Patients with HAP prospectively identified between June 2001 and May 2003 were included in the study if they (1) met the Centers for Disease Control and Prevention's definition for HAP, (2) were treated in the ICU within 1 day of the HAP diagnosis, and (3) required intubation acutely or had a bloodstream infection within 48 hours of the HAP diagnosis. RESULTS: The cohort included 219 patients, 83 of whom died (37.9%). Independent predictors of mortality included cancer (odds ratio [OR] = 4.2; 95% confidence interval [CI] = 1.7 to 10.5), age over 60 years (OR = 2.7; 95% CI = 1.3 to 5.6), APACHE-II score >15 (OR = 2.0; 95% CI = 1.0 to 4.1), and receiving care in the medical ICU (OR = 3.0; 95% CI = 1.1 to 8.2). The following predictors were associated with an increased time to extubation: receipt of vancomycin (1.81-fold increase; P = .001), immunocompromised status (1.92-fold increase; P = .07), and treatment in the surgical or neurosurgical ICU (1.95-fold increase, P = .01; 1.83-fold increase, P = .03). CONCLUSION: Vancomycin was associated with increased time to extubation. Alternatives to vancomycin for treating patients with acute, severe HAP should be studied.

Predictors of mortality in patients with bloodstream infection due to ceftazidime-resistant Klebsiella pneumoniae.

Bloodstream infection (BSI) due to multidrug-resistant Klebsiella is associated with high rates of morbidity and mortality. The aim of this study was to identify predictors of in-hospital mortality among patients with BSI due to ceftazidime-resistant (CAZ-R) Klebsiella pneumoniae at a tertiary care medical center. Patients with CAZ-R K. pneumoniae BSI were identified by our microbiology laboratory between January 1995 and June 2003. Clinical data were collected retrospectively. Logistic regression was used to identify independent predictors of all causes of in-hospital mortality. Of 779 patients with K. pneumoniae BSI, 60 (7.7%) had BSI due to CAZ-R K. pneumoniae; 43 (72%) of these were nosocomial infections. Pulsed-field gel electrophoresis identified a single predominant strain in 17 (28%) patients. The in-hospital mortality rate was 43% (n = 26). Among patients with CAZ-R K. pneumoniae BSI, those who died were similar to survivors with respect to demographic, clinical, and antimicrobial susceptibility characteristics. Only 43 (72%) patients received effective therapy within 5 days of BSI. In bivariable analysis, delay in initiation of effective therapy for >72 h after diagnosis of BSI was associated with death (P = 0.03). Strain genotype was not predictive of outcome. In multivariable analysis, delay in initiation of effective therapy for >72 h after diagnosis of BSI was an independent predictor of death (odds ratio, 3.32; 95% confidence interval, 1.07 to 10.3). Thus, among patients with BSI due to CAZ-R K. pneumoniae, a delay in the initiation of effective therapy of greater than 72 h after BSI was associated with a >3-fold increase in mortality risk.