Traveler's diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen.

BACKGROUND: Traveler's diarrhea in Thailand is frequently caused by Campylobacter jejuni. Rates of fluoroquinolone (FQ) resistance in Campylobacter organisms have exceeded 85% in recent years, and reduced fluoroquinolone efficacy has been observed. METHODS: Azithromycin regimens were evaluated in a randomized, double-blind trial of azithromycin, given as a single 1-g dose or a 3-day regimen (500 mg daily), versus a 3-day regimen of levofloxacin (500 mg daily) in military field clinics in Thailand. Outcomes included clinical end points (time to the last unformed stool [TLUS] and cure rates) and microbiological end points (pathogen eradication). RESULTS: A total of 156 patients with acute diarrhea were enrolled in the trial. Campylobacter organisms predominated (in 64% of patients), with levofloxacin resistance noted in 50% of Campylobacter organisms and with no azithromycin resistance noted. The cure rate at 72 h after treatment initiation was highest (96%) with single-dose azithromycin, compared with the cure rates of 85% noted with 3-day azithromycin and 71% noted with levofloxacin (P=.002). Single-dose azithromycin was also associated with the shortest median TLUS (35 h; P=.03, by log-rank test). Levofloxacin's efficacy was inferior to azithromycin's efficacy, except in patients with no pathogen identified during the first 24 h of treatment or in patients with levofloxacin-susceptible Campylobacter isolates, in whom it appeared to be equal to azithromycin. The rate of microbiological eradication was significantly better with azithromycin-based regimens (96%-100%), compared with levofloxacin (38%) (P=.001); however, this finding was poorly correlated with clinical outcome. A higher rate of posttreatment nausea in the 30 min after receipt of the first dose (14% vs. <6%; P=.06) was observed as a mild, self-limited complaint associated with single-dose azithromycin. CONCLUSIONS: Single-dose azithromycin is recommended for empirical therapy of traveler's diarrhea acquired in Thailand and is a reasonable first-line option for empirical management in general.

Chronic dialysis patients have high risk for pulmonary embolism.

Pulmonary embolism has been considered uncommon in chronic dialysis patients, but has not been adequately studied in a large population. In the US Renal Data System (USRDS), 76,718 patients presenting with end-stage renal disease (ESRD) between January 1, 1996, and December 31, 1996, were analyzed in an historical cohort study. The outcome was hospitalizations with a primary discharge diagnosis of pulmonary embolism (International Classification of Diseases, Ninth Revision code 415.1x) occurring within 1 year of the first ESRD treatment and excluding those occurring after renal transplantation. For dialysis patients, hospitalization rates for pulmonary embolism were obtained from the hospitalization section of the 1999 USRDS. For the general population, hospitalization rates for pulmonary embolism were obtained from the National Hospital Discharge Survey for 1996. Comorbidities from the Medical Evidence Form (Centers for Medicare and Medicaid Services, previously known as the Health Care Financing Administration; form 2728) were used to generate approximated stratified models of adjusted incidence ratios for pulmonary embolism (comorbidities could not be stratified for the general population). In 1996, the overall incidence rate of pulmonary embolism was 149.90/100,000 dialysis patients compared with 24.62/100,000 persons in the US population, with an age-adjusted incidence ratio of 2.34 in dialysis patients. Younger dialysis patients had the greatest relative risk for pulmonary embolism. The age-adjusted incidence ratio of pulmonary embolism after excluding dialysis patients with known risk factors for pulmonary embolism was 2.11. Ninety-five percent confidence intervals for all age categories in both models were statistically significant. Chronic dialysis patients have high risk for pulmonary embolism, independent of comorbidity.

Hospitalized congestive heart failure after renal transplantation in the United States.

PURPOSE: African Americans have increased risk for congestive heart failure (CHF) compared to Caucasians in the general population, but the risk of CHF in African American renal transplant recipients has not been studied in a national renal transplant population. METHODS: Therefore, 33,479 renal transplant recipients in the United States Renal Data System (USRDS) from 1 July, 1994 to 30 June, 1997 were analyzed in an historical cohort study of the incidence, associated factors, and mortality of hospitalizations with a primary discharge diagnosis of CHF [International Classification of Diseases-9 (ICD9) Code 428.x]. RESULTS: African American renal transplant recipients had increased age-adjusted risk of hospitalizations for congestive heart failure compared to African Americans in the general population [rate ratio 4.60, 95% confidence interval (CI) 4.59-4.62]. In logistic regression analysis, African American recipients had increased risk of congestive heart failure after renal transplantation, independent of other factors. Among other significant factors associated with congestive heart failure, the strongest were graft loss and allograft rejection. No maintenance immunosuppressive medications were associated with CHF. In Cox regression analysis patients hospitalized for CHF had increased all-cause mortality compared with all other recipients (hazard ratio 3.69, 95% CI, 2.23-6.10), but African American recipients with CHF were not at significantly increased risk of mortality compared to Caucasian recipients with CHF. CONCLUSIONS: African Americans recipients were at high risk for CHF after transplant independent of other factors. The reasons for this increased risk should be the subject of further study. All potential transplant recipients should receive particular attention for the diagnosis and prevention of CHF in the transplant evaluation process, which includes preservation of allograft function.

Factors associated with improved short term survival in obese end stage renal disease patients.

PURPOSE: In contrast to its role in the general population, obesity, defined as body mass index (BMI) > or = 30 kg/m(2), has been associated with improved survival in patients with end stage renal disease (ESRD). This apparent benefit has not been explained. METHODS: Using the United States Renal Data System (USRDS), we performed an historical cohort study on 151,027 patients initiated on ESRD therapy between January 1, 1995 and June 30, 1997, who never received renal transplants, and who had information sufficient to calculate BMI. We explored the association of various comorbidities present at the time of dialysis initiation (from HCFA Form 2728) with the presence of obesity by logistic regression, and the association of obesity with patient survival, including specific causes of death, by Cox regression adjusting for factors known to be associated with survival in this population. RESULTS: Obese patients had an unadjusted two-year survival of 68% compared with 58% for non obese patients. Obesity was independently associated with a reduced risk of mortality among chronic dialysis patients (adjusted hazard ratio (AHR) 0.75, 95% confidence interval, 0.72-0.78), after controlling for all comorbidities and risk factors. However, there were significantly adverse interactions among whites (AHR 1.22, 1.14-1.30, across all causes of death) and females (AHR 1.12, 1.04-1.20, entirely due to an increased risk of infectious death). CONCLUSIONS: Obesity in patients presenting with ESRD is associated independently with reduced all cause mortality; however, the relationship is complex and is stronger in African Americans. In addition, subgroup analysis suggests that obesity is associated with increased risk of infectious death in females.

Hospitalizations for cytomegalovirus disease after renal transplantation in the United States.

PURPOSE: Risk factors, sites, and mortality of hospitalized cytomegalovirus (CMV) disease in renal transplant recipients have not been studied in a national population. METHODS: Therefore, 33,479 renal transplant recipients in the United States Renal Data System from 1 July 1, 1994 to June 30, 1997 were analyzed in an historical cohort study of patients with a primary discharge diagnosis of CMV disease (ICD9 Code 078.5x). RESULTS: Renal transplant recipients had an incidence density of hospitalized CMV disease of 1.26/100 person years, and 79% of hospitalizations for CMV disease occurred in the first six months post transplant. The leading manifestation of hospitalized infection was pneumonia (17%). In logistic regression analysis controlling for transplant era, pre-transplant dialysis > or = 6 months, maintenance mycophenolate mofetil (MMF) therapy, and allograft rejection, but not induction antibody therapy, were significantly associated with hospitalized CMV disease. Compared with recipients with negative CMV serology (R-) who had donor kidneys with negative CMV serology (D-), D+/R- had the highest risk of hospitalization for CMV disease [adjusted odds ratio (AOR) 5.19, 95% confidence interval (CI) 3.89-6.93] followed by D+/R+ recipients, whereas D-/R+ were not at significantly increased risk. In Cox Regression analysis the relative risk of death associated with hospitalized CMV disease was 1.32 (95% CI 1.02-1.71). CONCLUSIONS: Even in modern era, renal transplant recipients were at high risk for hospitalizations for CMV disease, which were associated with decreased patient survival. Current prophylactic measures have apparently not reduced the high risk of D+/R- recipients. Prolonged pre-transplant dialysis and maintenance MMF should also be considered risk factors for hospitalized CMV infection, and prospective trials of prophylactic antiviral therapy should be performed in these subgroups.

Risk factors for pulmonary embolism in chronic dialysis patients.

BACKGROUND: Risk factors for pulmonary embolism (PE) in end stage renal disease (ESRD) patients have not been studied in a large population. METHODS: 375,152 patients in the United States Renal Data System initiated on dialysis between 1 January 1992 and 30 June 1997 were analyzed in an historical cohort study of hospitalized PE (ICD9 Code 415.1x) occurring prior to receipt of renal transplant. Cox regression models were used to analyze risk factors for PE in dialysis. Dialysis modality was analyzed in an intention to treat fashion, thus patients who changed modalities later were considered to have remained on the same modality. RESULTS: The incidence of pulmonary embolism did not increase over time. Independent risk factors for hospitalizations for PE were similar to those in the general population (older age, females, systemic lupus erythematosus, lower risk for Asians) with the addition of peritoneal dialysis (vs. hemodialysis, adjusted odds ratio 1.56, 95% CI 1.15-2.13), polycystic kidney disease, and congestive heart failure. Notably, in Cox regression analysis, no relation was seen with baseline laboratory results (hematocrit, serum albumin, serum creatinine) or comorbidity (except congestive heart failure) and PE risk. Dialysis patients with PE had increased mortality (hazard ratio 1.20, 95% confidence interval 1.08-1.33). CONCLUSIONS: The incidence of PE did not increase significantly in ESRD patients from 1992-1997. PE were associated with increased mortality. Peritoneal dialysis patients may have higher risk of PE than hemodialysis patients, and other high-risk groups were identified.

Hospitalizations for bacterial pneumonia after renal transplantation in the United States.

PURPOSE: Bacterial pneumonia has been cited as the leading cause of infectious death in renal transplant recipients but has not been studied in a national transplant population. SUBJECT AND METHODS: Retrospective analysis of the incidence, risk factors and mortality of hospitalized bacterial pneumonia (ICD9 Code 481.x486.x) for 33,479 renal transplant recipients in the United States Renal Data System transplanted from 1 July 1994-30 June 1997. RESULTS: Among all transplant recipients, 4.7% were hospitalized for a primary discharge diagnosis of pneumonia in the study period (2.86 episodes per 100 person years). 9.9% had bronchoscopy and 4.8% had open lung biopsy. A specific etiology was not identified in 72.5% of patients. The hospitalization rate for pneumonia and hazard for mortality due to hospitalized pneumonia were both constant over time. In logistic regression analysis, pneumonia prior to transplant (odds ratio 1.73, 95% confidence interval, 1.32-2.26), older recipient age, diabetes, delayed graft function, rejection (occurring at any time after transplant during the time of the study), duration of pre-transplant dialysis, and positive recipient cytomegalovirus serology were associated with pneumonia. In Cox Regression, hospitalization for pneumonia was associated with greater risk of mortality (hazard ratio 1.64, 95% CI, 1.42-1.89). CONCLUSIONS: Renal transplant recipients with a previous history of pneumonia are at increased risk for subsequent pneumonia, which is associated with substantially decreased patient survival. Given the low rate of specific etiologies identified in this study, invasive diagnosis may be underutilized in this population.

Environmental factors associated with larval habitats of malaria vectors in northern Kyunggi Province, Republic of Korea.

The larval habitats of malaria vectors near the Demilitarized Zone of the Republic of Korea (ROK) were sampled from June through September 2000 to determine larval abundance and to identify environmental factors associated with high larval density. Six primary habitats were identified: rice fields, irrigation ditches, drainage ditches, stream pools, irrigation pools, and marshes. Most habitats harbored similar densities of larvae until August and September, when population densities in rice fields declined and those in irrigation pools increased. The primary vector in the ROK, Anopheles sinensis, occurred in water with a wide range of values for environmental factors, including pH, total dissolved solids, percent of surface covered with floating vegetation, and nitrate and phosphate concentrations. No environmental factor or combination of factors were found that were predictive of high larval densities. This study suggests that larval Anopheles are capable of developing in a wide range of stagnant, freshwater habitats in northern Kyunggi Province, ROK.

Role of residual spraying for malaria control in Belize.

We studied the impact of reduced residual spraying in Belize by developing a logistic regression model on relationships between numbers of houses sprayed (mostly with DDT) and numbers of malaria cases. We defined the "minimum effective house spray rate" (MEHSR) as the level of spraying that will prevent increases in malaria rates for a defined population. Under the total coverage approach (all houses sprayed), the MEHSR for Belize was 134.6. The model also showed that the odds for decreasing malaria is 1.086 for each increase of 10 houses sprayed per 1,000 population. In further testing, highly significant and differential changes in malaria rates were documented for paired groups of years with house spray rates that were either above or below the MEHSR. Numbers of malaria cases since 1995 are used to show how stratification methods are used in Belize to spray fewer houses (at levels below the MEHSR of 134.6).

Survey for intestinal parasites in Belize, Central America.

A stool survey was carried out in 5 villages in the Toledo district of the Central American country of Belize. Eighty-two percent of a total population of 672 participated. The stools were examined by the formalin-ethyl-acetate concentration technique. Sixty-six percent of the population was found to have one or more intestinal parasites. The most common infection was hookworm (55%) followed by Ascaris lumbricoides (30%), Entamoeba coli (21%), Trichuris trichiura (19%), Giardia lamblia (12%), Iodamoeba beutschlii (9%), and Entamoeba histolytica/dispar (6%). Other parasites found were Entamoeba hartmani, Strongyloides stercoralis, Endolimax nana, Isospora belli, and Chilomastix mesnili. Children were more often infected than adults and more females had hookworm infections. Sixty percent of 111 households surveyed had dirt floors, 43% were without toilets, 35% of the houses were overcrowded, and 10% obtained drinking water from streams. Cross-tabulation and logistic regression analyses were used to identify risk and protective factors associated with parasitoses. The risk factors were: being in the Mayan Ketchi population group, and abtaining housework and drinking water from streams. Protective factors were: drinking treated water and the wearing of shoes.

Acute coronary syndromes after renal transplantation in patients with end-stage renal disease resulting from diabetes.

Coronary heart disease is the leading cause of death in both diabetes mellitus and end-stage renal disease. Although renal transplantation is known to reduce mortality in end-stage renal disease, its effect on the incidence of acute coronary syndromes is unknown. Using data from the United States Renal Data System, we studied 11,369 patients with end-stage renal disease due to diabetes enrolled on the renal and renal-pancreas transplant waiting list from 1 July 1994 to 30 June 1997. Cox nonproportional hazards regression models were used to calculate the adjusted, time-dependent relative risk for the most recent hospitalization for acute coronary syndromes (including acute myocardial infarction, unstable angina, or other acute coronary syndromes, ICD9 Code 410.x or 411.x) for a given patient in the study period. Demographics and comorbidities were controlled by using data from the medical evidence form (HCFA 2728). After renal transplantation, patients had an incidence of acute coronary syndromes of 0.79% per patient year, compared to 1.67% per patient year prior to transplantation. In comparison to maintenance dialysis, renal transplantation was independently associated with a lower risk for acute coronary syndromes (hazard ratio 0.38, 95% confidence interval, 0.30-0.49). Patients with end-stage renal disease due to diabetes on the renal transplant waiting list were much less likely to be hospitalized for acute coronary syndromes after renal transplantation. The reasons for this decreased risk should be the subject of further study.

Effect of donor factors on early graft survival in adult cadaveric renal transplantation.

Previous studies of the effect of donor factors on renal transplant outcomes have not tested the role of recipient body mass index, donor/recipient weight ratios and age matching, and other factors. We analyzed 20,309 adult (age 16 or older) recipients having solitary cadaveric renal transplants from adult donors from 1 July 1994 to 30 June 1998 in an historical cohort study (the 2000 United States Renal Data System) of death censored graft loss by the Cox proportional hazards models, which corrected for characteristics thought to affect outcomes. The only independently significant findings in Cox Regression analysis were a high donor/ recipient age ratio (> or = 1.10, e.g. a 55-year-old donor given to a recipient age 50years or younger, adjusted hazard ratio (AHR) 3.22, 95% confidence interval (CI) 2.36-4.39) and African American donor kidneys (AHR 1.64, 95% CI, 1.24-2.17). African American recipients and older donors were not at independently increased risk of graft failure in this model. Among donor factors, older donor kidneys given to younger recipients and donor African American kidneys were independently associated with graft loss in recipients of cadaver kidneys. The task for the transplant community should be to find the best means for managing all donor organs without discouraging organ donation.