[Show abstract][Hide abstract] ABSTRACT: Lassa fever is an acute viral hemorrhagic illness; the virus is endemic in West Africa and also of concern with regard to
bioterrorism. Transmission of Lassa virus between humans may occur through direct contact with infected blood or bodily secretions.
Oral administration of the antiviral drug ribavirin is often considered for postexposure prophylaxis, but no systematically
collected data or uniform guidelines exist for this indication. Furthermore, the relatively low secondary attack rates for
Lassa fever, the restriction of the area of endemicity to West Africa, and the infrequency of high-risk exposures make it
unlikely that controlled prospective efficacy trials will ever be possible. Recommendations for postexposure use of ribavirin
can therefore be made only on the basis of a thorough understanding and logical extrapolation of existing data. Here, we review
the pertinent issues and propose guidelines based on extensive review of the literature, as well as our experience in this
field. We recommend oral ribavirin postexposure prophylaxis for Lassa fever exclusively for definitive high-risk exposures.
These guidelines may also serve for exposure to other hemorrhagic fever viruses susceptible to ribavirin.
Full-text · Article · Nov 2010 · Clinical Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Background: Based on data obtained from a cohort of HIV-positive pregnant women, this study examines the risks of the regimens that are commonly relied upon for prevention of vertical HIV transmission in Haiti.
Methods: A cohort of pregnant women was analyzed, as part of a retrospective review of adult patients treated for HIV from the initiation of HAART (highly active antiretroviral therapy) treatment in 2004 until October 2008 at the “Hôpital Albert Schweitzer” in Deschapelles, Haiti.
Results: 290 charts were reviewed using random selection. 186 (64%) patients were female and 35 (19%) of those had a pregnancy during the period studied. 23% of women in the pregnancy cohort were diagnosed as a result of routine testing during pregnancy. If patients were not already on HAART when the pregnancy was diagnosed, then they were started on treatment at 28 weeks gestation, to be continued for a mean duration of approximately 12 weeks. One woman in the pregnancy cohort was on Efavirenz when her pregnancy was diagnosed. The majority of patients (74%) were treated with Zidovudine, Lamivudine and Nevirapine (NVP). 23% were treated with a regimen consisting of Stavudine, Lamivudine and Nevirapine. The average CD4 count at HAART initiation was 370 [25-1161]. 23% of women in the pregnancy cohort had side effects to their HAART regimen. Two (6%) had confirmed cases of Stevens-Johnson Syndrome. There were no reported cases of NVP-associated hepatotoxicity among the cohort studied.
Conclusion: The cohort studied had a significant incidence of side effects to the NVP-based regimens, though a lower incidence of hepatotoxicity than has been reported elsewhere. These results raise the issues of whether HAART regimens available for prevention of vertical HIV transmission in Haiti need to be expanded to include agents with safer side effect profiles and whether longer duration of Nevirapine therapy is sufficiently beneficial to warrant increased risks of these side effects.
[Show abstract][Hide abstract] ABSTRACT: Background: Adherence to HIV medication is difficult. Nonadherence to highly active antiretroviral therapy (HAART) has been shown to be the most important predictor of HIV progression and death. The purpose of this study was to identify the particular barriers to HAART adherence that exist in the population of patients with HIV receiving treatment at “Hôpital Albert Schweitzer (HAS)” in Deschapelles, Haiti.
Methods: A retrospective review was conducted of a random sample of existing charts of adult patients treated for HIV from 2004 until October 2008 at HAS in Deschapelles, Haiti.
Results: Two hundred and ninety charts were reviewed using random selection. Sixty-four percent of the patients were female and the mean age was 38 years, (range 19-70). Thirteen percent of the patients had a documented sexually transmitted disease and 42% had an opportunistic infection during their treatment. Risk behaviors were recorded for 49% of the patients; the most commonly reported risk factor was unprotected heterosexual contact (93%). Adherence data were available in 85% of the charts, 54% had adherence of greater than 90%, 46% had adherence less than 90%. Fifty-seven percent of patients had barriers to HAART. The most common barriers were: transportation (42%), forgetting to take medications (33%), food requirements (20%), side effects (20%) and running out of the pills (20%). The mean CD4 count recorded prior to HAART was 185 (95% CI 161-208) and after the first six months of HAART was 333 (95% CI 285-382), and in greater than 12 months following initiation of HAART; 437 (95% CI 399-475). Ten percent of patients in this review were documented to be deceased at their last contact.
Conclusion: Significant barriers to HAART adherence exist in patients with HIV at HAS in Deschapelles, Haiti. Effective interventions to address HAART adherence should focus on eliminating transportation barriers and addressing ways to prevent patients from forgetting their medications.
[Show abstract][Hide abstract] ABSTRACT: Background: Vancomycin has been widely used as the standard of therapy for all MRSA infections. Since MRSA bacteremia is associated with high mortality, we evaluated the role of vancomycin levels in MRSA bacteremia.
Methods: A retrospective chart analysis was conducted at Tulane University Hospital & Clinic of all patients admitted with MRSA bacteremia during the period of January 2005 to October 2007. Results: One hundred and seven patients with MRSA bacteremia were identified and 70 patients who received vancomycin had trough levels within 72 hours. Except for three isolates, all isolates were staphylococcal species phenotypically similar to community-associated S. aureus isolates and all isolates showed vancomycin susceptibility with a MIC < 2 mcg/ml. The median age of patients with MRSA bacteremia was 46 years, 52% were females and 72% African-Americans. Out of 70 patients, 26 had vancomycin trough levels >15 mcg/ml before 72 hours and 44 < 15 mcg/ml. Median time to MRSA clearance was 3 days in both groups (p= 0.457). The average duration of vancomycin treatment was 15 days in both groups (p= 0.460). Nephrotoxicity defined as a 50% increase in creatinine after 4 days of vancomycin was 4.5% for patients with vancomycin levels < 15mcg/ml compared to 15.4% in patients with vancomycin levels >15 mcg/ml (p= 0.186). Relapse defined as the occurrence of the phenotypically similar MRSA bacteremia within one year of clearance of bacteremia was observed in 4 (11.4%) patients with <15 mcg/ml trough levels compared to 1 (3.8%) patient with >15 mcg/ml trough levels (p=0.377). Conclusions: Clearance of MRSA bacteremia appeared to be similar in patients who had vancomycin levels above or below 15mcg/ml, but nephrotoxicity was almost 4-fold higher in patients with higher vancomycin trough levels, although this finding did not reach statistical significance.
[Show abstract][Hide abstract] ABSTRACT: Background:
CABM in children is associated with significant morbidity and mortality. Baseline clinical variables can be used to determine those at risk for an adverse clinical outcome.
This is a retrospective observational cohort study of 162 children, 4 weeks to 14 years of age, with a diagnosis of CABM at two New Orleans hospitals and at Yale-New Haven Hospital, CT from 1985 to 2005. Sociodemographic data, comorbidity, history and physical exam findings, and laboratory data were recorded at presentation to the emergency room. An adverse clinical outcome was defined as hearing impairment diagnosed by audiometry, neurological sequelae and/or death.
A total of 215 patients were identified, and 53 (25%) were excluded due to lack of audiometry. Of the 162 patients included for analysis, male sex (61%) and African-Americans (68%) predominated. There were 80 (49%) patients with an adverse outcome: 42 (26%) had hearing loss, 34 (21%) had neurological sequelae, and 20 (12%) died. The most common meningeal pathogens were H. influenzae (26%), Streptococcus pneumoniae (19%), Neisseria meningitides (4%), and Streptococcus agalactiae (3%). Bivariate analysis of variables associated with an adverse outcome included (p<0.05): 1) abnormal-host status (immunocompromised state or comorbidity), 2) history of otitis media, 3) abnormal neurological status (focal neurological deficit or seizure), 4) CSF protein more than 300mg/dl, and 5) CSF glucose less than 20 mg/dl. Adjunctive use of steroids (n=58, 36%), was not associated with a protective effect.
CABM is associated with neurological morbidity and mortality in the post-H. influenzae vaccine era. Clinical variables available at initial presentation can be predictive of an adverse clinical outcome.
[Show abstract][Hide abstract] ABSTRACT: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug-resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans.
Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose.
Tulane-Louisiana State University-Charity Hospital General Clinical Research Center in New Orleans.
126 healthy adults 21-45 years of age.
10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13.
Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation.
No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract-related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0-14.7 l/h versus 9.5-11.3 l/h; p < or = 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ.
These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics.
Full-text · Article · Jan 2007 · PLoS Clinical Trials
[Show abstract][Hide abstract] ABSTRACT: Background: Meropenem is commonly used with an antistaphylococcal antibiotic such as vancomycin as initial broad-spectrum empiric therapy in critically ill patients with nosocomial infections. In vitro synergy or antagonism with this combination has not been previously studied with ORSA.
Methods: We performed in vitro synergy testing on 10 pulsed field gel electrophoresis unique clinical blood isolates of ORSA collected from patients at Ochsner Clinic Foundation in 2004. The ORSA MICs were: MER 3- >32 μg/ml and VAN 1.5 - 2 μg/ml. An Etest® method previously presented (G. Pankey et al, Abstr. 229, 41st IDSA Meeting, 2003) and time kill assay (TKA) were used for synergy testing. Summation fractional inhibitory concentration (∑FIC) was calculated from the Etest method (synergy < 0.5, indifference >0.5 to <4, and antagonism >4). TKA was performed at 0 and 24 hrs. Synergy was defined as: >2 log10decrease in colony count at 24 hrs by the combination compared to the most active single agent. Antagonism was defined as: > 2 log10 increase in colony count at 24 hrs by the combination compared to the most active single agent.
Results: Sixty percent of isolates were found to be synergistic with MER + VAN by Etest but only 30% by TKA. Of the 5 isolates with discordant results, 4 were synergistic by Etest but indifferent by TKA (-1.0, -0.8, -0.1, and 1.0 log10 change in colony count), and 1 isolate was indifferent by Etest (∑FIC = 0.69) but synergistic by TKA (-2.0 log10 change in colony count).
Conclusions: In vitro synergy occurred in some ORSA isolates with MER + VAN using both methods. There was no evidence of in vitro antagonism. In vitro findings may or may not translate into in vivo usefulness of this combination against ORSA infections. Further studies with a larger number of isolates and an animal model are needed.