Quinupristin-dalfopristin resistance in Enterococcus faecium isolates from humans, farm animals, and grocery store meat in the United States.

Three hundred sixty-one quinupristin-dalfopristin (Q-D)-resistant Enterococcus faecium (QDREF) isolates were isolated from humans, turkeys, chickens, swine, dairy and beef cattle from farms, chicken carcasses, and ground pork from grocery stores in the United States from 1995 to 2003. These isolates were evaluated by pulsed-field gel electrophoresis (PFGE) to determine possible commonality between QDREF isolates from human and animal sources. PCR was performed to detect the streptogramin resistance genes vatD, vatE, and vgbA and the macrolide resistance gene ermB to determine the genetic mechanism of resistance in these isolates. QDREF from humans did not have PFGE patterns similar to those from animal sources. vatE was found in 35%, 26%, and 2% of QDREF isolates from turkeys, chickens, and humans, respectively, and was not found in QDREF isolates from other sources. ermB was commonly found in QDREF isolates from all sources. Known streptogramin resistance genes were absent in the majority of isolates, suggesting the presence of other, as-yet-undetermined, mechanisms of Q-D resistance.

Pneumonia in long-term care: a prospective case-control study of risk factors and impact on survival.

BACKGROUND: Pneumonia is a major cause of morbidity and mortality in long-term care facilities. Prior studies of pneumonia have failed to identify risk factors potentially amenable to intervention. Our objectives were to (1) identify modifiable risk factors for the occurrence of pneumonia and (2) determine the long-term impact of pneumonia on survival. METHODS: We performed a case-control study among residents of a Veterans Affairs long-term care facility. Case patients included all patients developing pneumonia from 2 days to 1 year after admission. Control subjects were matched for admission date, level of nursing care, and dependence in activities of daily living. Patients were followed up for 2 years or until death or discharge from the facility. RESULTS: We identified 104 case-control pairs. Risk factors significantly associated with pneumonia included witnessed aspiration (odds ratio, 13.9; 95% confidence interval, 1.7-111.0; P =.01), sedative medication (odds ratio, 2.6; 95% confidence interval, 1.2-5.4; P =.01), and comorbidity score (odds ratio, 1.2; 95% confidence interval, 1.0-1.4; P =.05). Mortality due to pneumonia was 23% at 14 days. Patients with pneumonia had a significantly higher mortality than did controls at 1 year (75% vs 40%; P<.001); survival curves converged at 2 years. In a Cox proportional hazards regression model, an episode of pneumonia was independently associated with mortality during follow-up (odds ratio, 2.6; 95% confidence interval, 1.7-3.9; P<.001). CONCLUSIONS: Among long-term care patients closely matched for age, level of dependency, and duration of institutionalization, an episode of pneumonia is associated with significant excess mortality that persists for up to 2 years. Two identified risk factors, large-volume aspiration and receipt of sedating medication, are potentially amenable to intervention.

Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. a prospective multicenter study.

BACKGROUND: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. DESIGN: Prospective observational study. SETTING: Four academic medical centers and a community hospital. PATIENTS: All patients with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.

Dyslipidaemia in HIV-infected patients: association with adherence to potent antiretroviral therapy.

Metabolic complications are being increasingly recognized among HIV-infected patients treated with potent combination antiretroviral therapies. We sought to assess the association of dyslipidaemia with adherence to protease inhibitor (PI) therapy and with the markers of clinical response to antiretroviral therapy (CD4 count, HIV RNA viral level) through a prospective, cross-sectional cohort study. Fifty-six HIV-infected patients who were already on, or who were started on PI-containing antiretroviral therapy were monitored for the development of dyslipidaemias. Therapy with PI-containing antiretroviral therapy was significantly associated with elevated serum triglyceride level (>250 mg/dl) (52% vs 8%, P=0.001). Patients with an adherence rate of at least 80% to a PI-containing regimen were significantly more likely to have elevated low density lipoprotein (LDL) cholesterol level as compared to patients with an adherence rate of <80% (79% vs 26%, P=0.03). Patients with an adherence rate of at least 80% to a PI-containing regimen were also significantly more likely to have severe hypertriglyceridaemia (>800 mg/dl) as compared to patients with an adherence rate of <80% (21% vs 4%, P=0.04). Viral load at the last study visit did not correlate with total cholesterol (r=-0.39, P=0.30), LDL cholesterol (r=0.57, P=0.30), or triglyceride level (r=0.55, P=0.20). However, there was a significant correlation between the last viral load and high density lipoprotein (HDL) cholesterol (r=0.79, P=0.035), i.e. lower viral load was associated with higher HDL cholesterol level. In conclusion, dyslipidaemia in patients with HIV infection was significantly associated with adherence to PI-containing antiretroviral therapy. Patients who are adherent to PI-containing regimens at least 80% of the time warrant close monitoring for the development of dyslipidaemia.

Topical antibiotic prophylaxis for bacteremia after dental extractions.

OBJECTIVE: Current prophylaxis for endocarditis in patients undergoing dental procedures consists of oral administration of amoxicillin. There is concern that the risk of anaphylaxis from systemically administered antibiotics might approach the incidence of endocarditis. Emergence of resistance among bacteria is also favored by systemically administered antibiotics. The present study was designed to assess the efficacy of topical amoxicillin given prophylactically as a mouthwash in reducing the incidence of bacteremia after dental extraction. STUDY DESIGN: Thirty-six outpatients in a dental clinic were randomized in a 3:2:2 ratio to experimental prophylaxis of topical amoxicillin (3 g per mouthwash rinse; 15 patients), standard prophylaxis of oral amoxicillin (3 g in a single dose; 11 patients), or no prophylaxis (10 patients), respectively. Patients were stratified by severity of periodontal disease and number of teeth extracted. Data were analyzed for differences in the incidence of bacteremia by means of the 2-tailed Fisher exact test. RESULTS: Breakthrough bacteremia after dental extraction was observed in 60% (6 of 10 patients) who received topical amoxicillin and in 89% (8 of 9 patients) who received no prophylaxis (P =.30). By comparison, breakthrough bacteremia after dental extraction was observed in 10% (1 of 10 patients) who received standard prophylaxis with oral amoxicillin (60% vs 10%; P =.05). CONCLUSIONS: Topical amoxicillin decreased the incidence of bacteremia in comparison with no prophylaxis, but statistical significance was not achieved (P =.30). Topical amoxicillin was significantly less effective than standard prophylaxis with oral amoxicillin in decreasing the incidence of bacteremia after dental extractions.

Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

BACKGROUND: Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. OBJECTIVE: To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. DESIGN: Prospective, observational study. SETTING: HIV clinics in a Veterans Affairs medical center and a university medical center. PATIENTS: 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). MEASUREMENTS: Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). RESULTS: During the study period, 45,397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. CONCLUSIONS: Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.

Azithromycin vs cefuroxime plus erythromycin for empirical treatment of community-acquired pneumonia in hospitalized patients: a prospective, randomized, multicenter trial.

OBJECTIVE: To compare the efficacy and safety of azithromycin dihydrate monotherapy with those of a combination of cefuroxime axetil plus erythromycin as empirical therapy for community-acquired pneumonia in hospitalized patients. METHODS: Patients were enrolled in a prospective, randomized, multicenter study. The standard therapy of cefuroxime plus erythromycin was consistent with the American Thoracic Society, Canadian Community-Acquired Pneumonia Consensus Group, and Infectious Disease Society of America consensus guidelines. The doses were intravenous azithromycin (500 mg once daily) followed by oral azithromycin (500 mg once daily), intravenous cefuroxime (750 mg every 8 hours), followed by oral cefuroxime axetil (500 mg twice daily), and erythromycin (500-1000 mg) intravenously or orally every 6 hours. Randomization was stratified by severity of illness and age. Patients who were immunosuppressed or residing in nursing homes were excluded. RESULTS: Data from 145 patients (67 received azithromycin and 78 received cefuroxime plus erythromycin) were evaluable. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 19% (28/145) and 13% (19/145), respectively. The atypical pathogens accounted for 33% (48/145) of the etiologic diagnoses; Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumoniae were identified in 14% (20/ 145), 10% (15/145), and 9% (13/145), respectively. Clinical cure was achieved in 91% (61/67) of the patients in the azithromycin group and 91% (71/78) in the cefuroxime plus erythromycin group. Adverse events (intravenous catheter site reactions, gastrointestinal tract disturbances) were significantly more common in patients who received cefuroxime plus erythromycin (49% [30/78]) than in patients who received azithromycin (12% [8/67]) (P<.001). CONCLUSIONS: Treatment with azithromycin was as effective as cefuroxime plus erythromycin in the empirical management of community-acquired pneumonia in immunocompetent patients who were hospitalized. Azithromycin was well tolerated.

Natural history of HIV-1 infection.

Infection with the human immunodeficiency virus type 1 (HIV-1) results in progressive loss of immune function marked by depletion of the CD4+ T-lymphocytes, leading to opportunistic infections and malignancies characteristic of AIDS. Although both host and viral determinants influence the rate of disease progression, the median time from initial infection to the development of AIDS among untreated patients ranges from 8 to 10 years. The clinical staging of HIV disease and the relative risk of developing opportunistic infections historically relied on the CD4+ T-lymphocyte counts. Although more recent studies have shown the importance of viral load quantitation in determining the rate of disease progression, it is still useful to categorize HIV disease stage on the basis of the degree of immunodeficiency: early disease (CD4+ > 500 cells/mL), mid-stage disease (CD4+ between 200 and 500 cells/mL), and end-stage disease (CD4+ < 50 cell/mL). This article reviews the natural history of HIV disease at each stage of HIV-1 infection with emphasis on acute infection and the major virologic and immunologic determinants of disease progression.

Legionella as a cause of severe pneumonia.

Legionella pneumophila has been found to be a common cause of community-acquired pneumonia in patients who required intensive care unit (ICU) admission. In many studies, the clinical manifestations for Legionnaires' disease were more severe and the mortality was higher when compared with pneumonias of other etiology. However, this may be due to delay in diagnosis and suboptimal antibiotic therapy, rather than enhanced virulence of L. pneumophila. A syndromic approach using high fever, diarrhea, mental status changes, hyponatremia, etc., may be useful in suggesting the correct diagnosis in patients with severe pneumonia, but this remains to be validated. The availability of Legionella diagnostic microbiology testing in-house (rather than being sent to an outside reference laboratory) maximizes the ability to correctly diagnose Legionnaires' disease. All patients with community-acquired pneumonia admitted to an ICU should undergo Legionella testing using the urinary antigen and culture on selective media. Moreover, we recommend routine cultures of the hospital water supply once a year (regardless of whether a case of nosocomial Legionnaires' disease has ever been diagnosed). If Legionella is found in the water supply, all patients with nosocomial pneumonia should undergo diagnostic tests for Legionella; empiric anti-Legionella antibiotics should be administered pending definitive diagnosis.

Macrolides are ideal for empiric therapy of community-acquired pneumonia in the immunocompetent host.

We propose that macrolides, especially the newer macrolides (azithromycin, clarithromycin, roxithromycin), are ideal agents for community-acquired pneumonia in the immunocompetent host who is not a resident of a nursing home or long-term care facility. Macrolides have proven effective in clinical trials against typical and atypical pathogens; thus, unlike beta-lactam agents, they can be given as monotherapy. Streptococcus pneumoniae isolates exhibiting high-level resistance to penicillin and cephalosporins pose a problem not only for the macrolides, but also for quinolones, tetracyclines, and most other beta-lactam agents. The tetracycines, quinolones, and beta-lactam agents have broader spectrum activity against aerobic gram-negative bacilli, which are uncommon pathogens of community-acquired pneumonia in the immunocompetent host. This broader spectrum is not only superfluous, but the potential of emergence of resistant bacteria is enhanced unnecessarily. Serious adverse reactions to the macrolides are rare. The newer macrolides have improved bioavailability and improved pharmacokinetics such that once- or twice-daily dosing regimens can be used. Finally, a comparison of the costs of macrolides to quinolones and beta-lactam agents (especially cephalosporins) show that the oral macrolides are among the least expensive antibiotics that can be prescribed for pneumonia. Thus, macrolides seem to be the ideal empiric antibiotic for community-acquired pneumonia based on spectrum of activity, safety, and cost.

Factors associated with hypertension in Nigerian civil servants.

BACKGROUND: Study of hypertension in segments of West African populations in transition toward Westernization may lead to better understanding of the high risk for hypertension among Westernized blacks. METHODS: Five hundred fifty-nine urban civil servants, ages 25-54, were recruited from six ministries of Bendel State, Nigeria. Blood pressure, physical measurements, urinary protein and glucose, fasting blood glucose, and demographic data were collected at the workplace. Subjects were classified as senior staff (professionals or administrators) or junior staff (non-administrators). RESULTS: Among 172 male senior staff, the age-adjusted rate of hypertension (diastolic blood pressure > or = 90 mm Hg, systolic blood pressure > or = 140 mm Hg, or on an antihypertensive medication) was 43% and occurrence rose dramatically from 21 to 63% across age groups 25-34 to 45-54, respectively. Among 266 male junior staff, the age-adjusted rate of hypertension was 23%, and occurrence did not rise with age. Logistic regression showed that body mass index (kg/m2), age, alcohol drinking, and being senior staff were all independently related to hypertension in men. On the other hand, the age-adjusted rate of hypertension in 121 women was 20% and was significantly related only to body mass index. CONCLUSION: Male urban civil servants appeared to have a risk for hypertension similar to that of U.S. black males. Age, body mass index, alcohol drinking, and other unidentified factors related to higher socioeconomic status were strong determinants of hypertension in this population.

Factors related to blood pressure among urban Nigerian workers.

This cross-sectional study of urban, Nigerian civil servants found that age, body mass index, alcohol drinking and high socioeconomic status were all positively and independently related to blood pressure among 438 males. Among 121 females, only body mass index was significantly related to blood pressure.

Blood pressure and other cardiovascular disease risk factors in black adults with sickle cell trait or glucose-6-phosphate dehydrogenase deficiency.

In this study, we examined the relationship of two common genetic markers in black populations, sickle cell trait and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, to cardiovascular risk factors. The subjects were Nigerian civil servants in Benin City, Nigeria. We measured blood pressure, height, weight, sickle cell hemoglobin, G-6-PD, proteinuria, microalbuminuria and fasting serum cholesterol, high-density lipoprotein cholesterol (HDL), triglycerides, apoprotein (APO) AI, and APO B. Data were collected on age, alcohol consumption, cigarette smoking, job status, and years lived in an urban area. There were 257 males (3 SS hemoglobin, 73 AS, 181 AA) and 69 females (23 AS, 46 AA). In comparing cardiovascular risk factors, males differed only in percent of smokers (31.5 in AS vs. 17.8 in AA, P less than 0.01). Among females, only high-density lipoprotein (HDL) cholesterol differed (61.5 mg/dl in AS vs. 52.4 in AA, P less than 0.01). We hypothesize that females with sickle cell trait are more likely to use oral contraceptives than nontrait females. If so, the high-estrogen oral contraceptives available in Nigeria could elevate HDL. G-6-PD deficiency status among males (52 deficient, 207 nondeficient) and females (1 deficient, 5 carriers, 65 nondeficient) was not related to any of the cardiovascular risk factors. We conclude that sickle cell hemoglobin trait and G-6-PD deficiency are not useful genetic markers for risk factors for cardiovascular disease.