Multisystem inflammatory syndrome in an adult with severe hypoxaemia and thyroiditis responsive to corticosteroid and interleukin 6 inhibitor treatment.

Multisystem inflammatory syndrome in adults (MIS-A) has been reported as a rare but severe consequence of COVID-19 infection. Adult patients were more likely to present with hypotension and cardiac illness when compared with multisystem inflammatory syndrome in children. Although the exact prevalence of MIS-A is unknown, more cases have been observed in men and younger adults. The pathophysiology of MIS-A is also unclear, but is thought to be caused by a delayed, dysregulated immune response. Given no established guideline for treatment of MIS-A, treatment has been based on case reports. We present a case of MIS-A in a woman in her 60s who had severe hypotension, progressive dyspnoea, massive pleural effusion, hypoxaemia, thyroiditis and multiple organ failure, which dramatically improved after treatment with corticosteroid and interleukin 6 inhibitor.

Detection of Leishmania siamensis DNA in saliva by polymerase chain reaction.

Polymerase chain reaction was used to detect Leishmania siamensis DNA from clinical samples collected from six leishmaniasis patients during 2011-2012. The samples used in this study came from bone marrow, blood, buffy coat, saliva, urine, and tissue biopsy specimens. Saliva was a good source for L. siamensis DNA by polymerase chain reaction. L. siamensis DNA was also found in saliva of an asymptomatic case-patient. Levels of L. siamensis DNA in saliva decreased until being undetectable after treatment. These levels could be used as a marker to evaluate efficacy of the treatment. A larger study is needed to evaluate this method as a screening and survey tool to study the silent background of Leishmania infection among the at-risk population.

Virological and immunological responses of efavirenz-based HAART regimen initiated in HIV-infected patients at CD4 < 100 versus CD4 > or = 100 cells/mm3.

OBJECTIVE: To compare virological and immunological responsiveness of efavirenz (EFV)-based highly active anti retroviral therapy (HAART) between patients with baseline CD4 < 100 and CD4 > or = 100 cells/mm3. MATERIAL AND METHOD: A prospective cohort study in antiretroviral-naive HIV-infected patients was conducted between February and April 2002. Donated HAART regimen, consisting of stavudine, didanosine, and EFV was initiated. The primary outcome was time to undetectable HIV RNA, < 50 copies/mL. Patients were followed up every 12 weeks until 48 weeks (the end of the study). RESULTS: Forty-six patients were included, 21 patients for CD4 < 100 cells/mm3 and 25 patients for CD4 > or = 100 cells/mm3. Median CD4 cell counts of these corresponding groups were 26.5 and 177 cells/mm3. Patients' characteristics were similar between the two groups except CD4. The probability of undetectable HIV RNA at 12, 24, 36, and 48 weeks were 57.1% (95% CI, 37.7-78.1%), 76.2% (95% CI, 56.9-91.3%), 80.9% (95% CI, 62.3-94.0%), and 90.5% (95% CI, 68.9-99.1%) for the former group; and 64.0% (95% CI, 45.8-81.8%), 92.0% (95% CI, 77.5-98.6%), 96.0% (95% CI, 83.0-99.7%), and 96.0%.(95% CI, 83.0-99.7%) for the latter group. Median time to undetectable HIV RNA was 12 weeks for both groups. Median CD4 change at 48 weeks was 171 and 132 cells/mm3, respectively (p = 0.232). The adverse events were similar between the two groups. CONCLUSION: Initiation of EFV-based HAART regimen in HIV-infected patients at CD4 < 100 and > or = 100 cells/ mm3 gains similar immunological and virological response.

Efavirenz 600 mg/day versus efavirenz 800 mg/day in HIV-infected patients with tuberculosis receiving rifampicin: 48 weeks results.

The potential of drug-drug interaction between efavirenz and rifampicin is a major concern in the treatment of HIV and tuberculosis. The optimal efavirenz dosage is still unclear. Our randomized control trial study recently reported the similar efavirenz level between efavirenz 600 and 800 mg/day in HIV-infected patients receiving rifampicin. We report the similar virological and immunological outcomes at 48 weeks between the two groups. Efavirenz 600 mg/day should be sufficient for concurrent use with rifamipicin.

Skin and soft-tissue infections among tsunami survivors in southern Thailand.

Among 777 patients transferred to 4 hospitals in Bangkok from southern Thailand after the tsunami of 26 December 2004, there were 515 with skin and soft-tissue infections. The most common organisms isolated were Aeromonas species (145 [22.6%] of 641 isolates from 305 patients). Most isolates were susceptible to aminoglycosides, third- and fourth-generation cephalosporins, quinolones, and imipenem but were resistant to amoxicillin-clavulanate and first-generation cephalosporins.

Efavirenz levels and 24-week efficacy in HIV-infected patients with tuberculosis receiving highly active antiretroviral therapy and rifampicin.

BACKGROUND: Concomitant use of efavirenz and rifampicin is common for treatment of HIV and tuberculosis. Plasma efavirenz levels can be reduced by rifampicin, but the appropriate daily dosage of efavirenz is unclear. METHODS: HIV-infected patients with active tuberculosis, receiving rifampicin > 1 month, were randomized to receive stavudine and lamivudine plus efavirenz 600 or 800 mg daily. Plasma efavirenz levels were measured (at 12 h after dosing and on day 14) by high-performance liquid chromatography. Plasma HIV RNA was assessed at 16 and 24 weeks after antiretroviral therapy. RESULTS: Baseline characteristics were comparable in the 84 patients (two groups of 42). Median plasma efavirenz levels were 3.02 mg/l (range, 0.07-12.21) in the 600 mg group and 3.39 mg/l (range, 1.03-21.31) in the 800 mg group (P = 0.632). Plasma efavirenz levels were < 1 mg/l in 3 of 38 (7.9%) patients in the 600 mg group and in none of the 800 mg group (P = 0.274). Approximately 40 and 45% of patients had efavirenz levels > 4 mg/l, respectively. There was no significant difference in time to HIV RNA < 50 copies/ml (P = 0.848). CONCLUSIONS: Median plasma efavirenz levels were comparable among both groups. Efavirenz 600 mg/day should be sufficient for most Thai HIV-infected patients receiving rifampicin with body weight approximately 50 kg. These results may not be applicable to other ethic populations who have higher body weights. However, the study of long-term virological and immunological outcomes is needed and under further investigation.

Initiation of highly active antiretroviral therapy in advanced AIDS with CD4 < 50 cells/mm3 in a resource-limited setting: efficacy and tolerability.

In developing countries, patients often present late with advanced AIDS and a very low CD4 cell count. A retrospective cohort study was conducted in HIV-infected patients who had been initiated into highly active antiretroviral therapy (HAART) with CD4 cell count < 50 cells/mm3. There were 159 patients of mean age 36.6 years and 60.4% had previous major opportunistic infections. Mean CD4 was 22 cells/mm3 and 80% had HIV RNA > 100,000 copies/mL. The majority of HAART regimens is non-nucleoside reverse transcriptase inhibitor-based (81.8%). In as-treated analysis, 50, 71.2, 79.7, 79.4, and 80.1% of patients achieved undetectable HIV RNA (< 50 copies/mL) at 12, 24, 36, 48, and 60 weeks, respectively. The corresponding mean CD4 counts were 95, 125, 166, 201, and 225 cells/mm3. Twenty two patients (13.8%) had adverse drug events and half of these had to discontinue HAART. Initiation of HAART in advanced AIDS with CD4 cell count < 50 cells/mm3 is effective, safe, and well tolerated and should not be delayed.

The TREAT Asia HIV Observational Database: baseline and retrospective data.

BACKGROUND: Relatively little is known regarding HIV disease natural history and response to antiretroviral treatments among Asian people infected with HIV. The Therapeutics Research, Education, and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) is a recently established collaborative observational cohort study that aims to assess HIV disease natural history in treated and untreated patients in the Asia-Pacific region. METHODS: Observational data are collected on HIV-infected patients from 11 sites in the Asia-Pacific region. Data are centrally aggregated for analyses, with the first baseline and retrospective data transferred in September 2003. Retrospective data were analyzed to assess the response to highly active antiretroviral treatment (HAART) over a 6-month period in terms of changes in CD4 count and proportions of patients achieving an undetectable HIV viral load (<400 copies/mL). RESULTS: By the end of May 2004, 1887 patients had been recruited to the TAHOD. Seventy-two percent of patients were male, with median age 36 years. Seventy-eight percent of patients reported HIV infection through heterosexual contact. Forty-three percent of patients had a previous AIDS diagnosis, of whom 55% had tuberculosis. The mean 6-month CD4 count increase was 115 cells/muL (SD=127) after starting triple-combination therapy. Smaller CD4 count increases were associated with a higher CD4 count before starting treatment, prior treatment with monotherapy or double therapy, and treatment with a HAART regimen containing a nucleoside reverse transcriptase inhibitor (NRTI) and/or protease inhibitor (PI) but without a nonnucleoside reverse transcriptase inhibitor (NNRTI). Five hundred and ninety-eight patients started HAART and had a viral load assessment at 6 months, with 69% attaining an undetectable viral load. Older patients, patients not exposed to HIV through heterosexual contact, and patients treated with HAART containing NRTIs and NNRTIs but without PIs were found to be more likely to achieve an undetectable level. CONCLUSION: Analyses of retrospective data in the TAHOD suggest that the overall response to HAART in Asian populations is similar to that seen in Western countries.

Case report: Brucellosis: a re-emerging disease in Thailand.

Brucellosis is a zoonotic disease prevalent in many countries, but it has been reported only once in Thailand, 36 years ago. We describe here two consecutive cases of brucellosis in Bangkok, Thailand. Both cases presented with prolonged fever and weight loss. Blood cultures taken from 2 patients yielded Brucella melitensis. The slide agglutination test of blood samples were also positive, with a titer of 1:64 for antibodies to Brucella. The first patient responded to a combination of doxycycline, gentamicin, and ciprofloxacin; the other responded to doxycycline and rifampicin. Brucellosis is a potential public health threat, therefore, preventive measures should be actively implemented. This clinical syndrome should be included in the differential diagnosis of patients presenting with prolonged fever, particularly those with contact to animals which could serve as reservoirs.

Aspergillosis of the central nervous system: a catastrophic opportunistic infection.

The clinical features and outcome of the treatment of aspergillosis of the central nervous system (CNS) in Thai patients are presented. The patients who were diagnosed as having CNS aspergillosis by tissue biopsy or culture from January 1, 1991 to December 31, 2000 were retrospectively reviewed. The study variables including age, sex, underlying disease, symptoms and signs, neuro-imaging studies, pathological findings and outcome of treatment, are described. There were seven cases of aspergillosis of the central nervous system. Four patients were male. The median age was 65 years (range 36-78 years). The most common underlying disease was diabetes mellitus (4/7; 57.1%). Two patients (28.6%) had no underlying disease. The most common primary site of infection was the paranasal sinuses (6/7; 85.7%). The most common clinical presentation was headache (6/7; 85.7%). Common neurological signs included multiple cranial nerve palsies (5/7; 71.4%) and alteration of consciousness (3/7; 42.9%). The median duration of the symptoms prior to admission was 60 days (range 8-180 days). All patients were treated with intravenous antifungal agents at high doses. Extensive surgery was performed in 6 patients. The mortality rate was very high (6/7; 85.7%). The median time from diagnosis and treatment to death was 53 days (22-720 days). Aspergillosis of the CNS should be considered in those with clinical features of headache, multiple cranial nerve palsies and alteration of consciousness accompanied by sinusitis, especially in elderly and diabetic patients. It remains a catastrophic opportunistic infection in spite of the current intensive and aggressive treatment.

Triple nucleoside treatment with abacavir plus the lamivudine/zidovudine combination tablet (COM) compared to indinavir/COM in antiretroviral therapy-naïve adults: results of a 48-week open-label, equivalence trial (CNA3014).

OBJECTIVE: An equivalence (non-inferiority) trial comparing antiviral response, tolerability, and adherence with a triple nucleoside regimen containing abacavir 300 mg (ABC) plus a lamivudine 150-mg/zidovudine 300-mg combination tablet (COM) twice daily vs. a regimen containing the protease inhibitor indinavir (IDV) 800 mg three times daily plus COM twice daily (IDV/COM) in antiretroviral-naïve, HIV-infected patients. METHODS: Adult patients with plasma HIV-1 RNA levels > or = 5000 copies/mL and CD4+ cell counts > or = 100 cells/mm(3) were randomized to receive open-label ABC/COM (n = 169) or IDV/COM (n = 173) for 48 weeks. The intent-to-treat (ITT) population was the primary population evaluated. ITT: switch/missing equals failure (ITT: S/M = F) and as-treated (AT) analyses were used for assessing the proportion of patients achieving plasma HIV-1 RNA level < 400 and < 50 copies/mL at each clinic visit. In the ITT: S/M = F analysis, patients who switched treatment or had missing values were considered treatment failures; the AT analysis examined virologic data only while patients received study treatment. ABC/COM was considered equivalent (non-inferior) to IDV/COM if the lower limit of the 95% confidence intervals (CIs) about the difference in proportions of ABC/COM- vs. IDV/COM-treated patients attaining plasma HIV-1 RNA < 400 copies/mL exceeded -15% at week 48. RESULTS: The study population was diverse with respect to ethnicity (38% Asian, 27% Hispanic, 28% white, 3% black, 4% other) and gender (39% women, 61% men). Baseline median HIV-1 RNA was 4.80 log(10) copies/mL and CD4+ cell count was 315 cells/mm(3). ABC/COM met the criterion of equivalence to IDV/COM. In the ITT: S/M = F analysis at Week 48, a greater proportion of ABC/COM-treated patients achieved HIV-1 RNA < 400 copies/mL (66% [109/164] vs. 50% [82/165]; treatment difference 16.6%, 95% CI (6.0, 27.2), p = 0.002) and HIV-1 RNA < 50 copies/mL (60% [99/164] vs. 50% [83/165]; treatment difference 9.6%, 95% CI [-1.1, 20.2]), whereas the AT analysis showed similar proportions achieving these endpoints (< 400 copies/mL: 85 vs. 83%; < 50 copies/mL: 79 vs 81%). Comparable proportions of patients with screening HIV-1 RNA values > 100 000 copies/mL achieved HIV-1 RNA < 400 copies/mL (ABC/COM: 60% [35/58]; IDV/COM: 51% [33/65]; treatment difference 9.6%, 95% CI [-7.9, 27.1]; ITT: S/M = F analysis). A significantly greater proportion taking ABC/COM were > or = 95% adherent (72% [109/151] vs. 45% [70/154] with IDV/COM, p < 0.001). Median increases from baseline in CD4+ cell counts were similar in the two treatment groups (+148 vs. +152 cells/mm(3)). Significantly more patients on IDV/COM reported drug-related adverse events (87% [142/165] vs. 65% [108/164] with ABC/COM, p < 0.001), similar proportions discontinued treatment due to adverse events (13 vs. 10%), and a slightly greater proportion in the ABC/COM group reported serious adverse events (13 vs. 8%). About half of the latter comprised suspected ABC-related hypersensitivity reactions (overall rate, 6%). Most adverse events were gastrointestinal in nature in both treatment groups. CONCLUSION: ABC/COM was at least equivalent to IDV/COM over 48 weeks in the treatment of antiretroviral-naïve patients. ABC/COM was associated with a significantly higher adherence rate and lower incidence of drug-related adverse events than IDV/COM. The study was limited in that it was not powered to determine equivalence of treatments within high vs. low viral load strata, adherence was not monitored electronically, and bias could not be ruled out due to the open-label study design.

Predictors of adherence and virologic outcome in HIV-infected patients treated with abacavir- or indinavir-based triple combination HAART also containing lamivudine/zidovudine.

OBJECTIVES: To compare dosing convenience and adherence with abacavir (ABC) 300 mg plus a fixed-dose lamivudine 150 mg/zidovudine 300 mg combination tablet (COM) twice daily versus indinavir (IDV) plus COM twice daily in treatment-naïve, HIV-1-infected adults; and to evaluate the association among difficulty taking antiretroviral regimens, adherence, and virologic efficacy. METHODS: An open-label, randomized, multicenter, international study compared the COM/ABC and IDV/COM regimens with respect to self-reported adherence and regimen convenience over 48 weeks. Logistic regression analysis (LRA) was done on a patient sub-sample from both groups to evaluate predictors of adherence and virologic response at last time-point on randomized therapy (LTORT). RESULTS: The study population was diverse with respect to ethnicity (38% Asian, 27% Hispanic, 28% white, 3% black, 4% other) and gender (39% women, 61% men). Baseline median HIV-1 RNA was 4.80 log(10) copies/mL and CD4+ cell count was 315 cells/mm(3). Of 329 patients who were randomized and received treatment, 315 (96%) provided adherence data. Significantly more patients in the ABC/COM group than in the IDV/COM group reported > or = 95% adherence to therapy (76 vs 58%, p < 0.001) and no difficulty in taking their regimen (91 vs 61%, p < 0.001). In both groups, the highest probability of HIV-1 RNA < 400 copies/mL occurred when median adherence was > or = 95%. The probability of HIV-1 RNA < 400 copies/mL declined more rapidly in the IDV/COM group as adherence rates decreased. LRA showed that no difficulty taking any of the drugs in the regimen, ABC/COM treatment group, and male gender were independent significant predictors of > or = 95% adherence (p < 0.05). Median adherence and baseline HIV-1 RNA were significant predictors of HIV-1 RNA < 400 copies/mL (p < 0.05). CONCLUSIONS: Patients reported greater ease of use and superior adherence to ABC/COM than IDV/COM. Patient-reported difficulty taking drugs in a regimen was predictive of reduced adherence, and both of the latter factors were predictive of poorer virologic outcome. Adherence levels of > or = 95% in both treatment groups maximized the probability of patients achieving an HIV-1 RNA < 400 copies/mL.

Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV.

BACKGROUND: Atazanavir, an azapeptide protease inhibitor (PI), has pharmacokinetics that allow once-daily dosing, and it is not associated with significant PI-associated dyslipidemia. METHODS: A randomized, double-blind, double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV RNA level. The primary efficacy end point was the proportion of treated patients with HIV RNA levels <400 copies/mL through week 48. RESULTS: At week 48, HIV RNA levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of patients receiving efavirenz (intent-to-treat, difference; 95% confidence interval: 5.2%; -1.2%, 11.7%). Median CD4 cell counts increased at comparable magnitudes and rates in the 2 treatment arms (mean change at week 48: 176 cells/mm with atazanavir, 160 cells/mm with efavirenz). Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol, fasting low-density lipoprotein cholesterol, or fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir treatment did not increase fasting glucose or insulin levels. CONCLUSIONS: For initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine.

Sweet's syndrome: a reaction to non-tuberculous mycobacterial infections.

Sweet's syndrome has been reported to be associated with many underlying conditions, such as non-tuberculous mycobacterial infections (NTMI). In the literature, only twelve patents with Sweet's syndrome in association with NTMI have been reported (most of the patients were from Thailand). Here, the authors report six more patients who developed Sweet's syndrome as a reaction to NTMI. Four patients had Mycobacterium chelonae/abscessus group infection; one patient had been infected with Mycobacterium avium complex first and became infected with M. chelonae/abscessus group 17 months later; and, the other one had Mycobacterium fortuitum infection. In each patient, the skin lesions of Sweet's syndrome relapsed many times while they still had NTMI, and these lesions usually responded well to short courses of systemic steroids without any deterioration of NTMI.

Elective cesarean delivery plus short-course lamivudine and zidovudine for the prevention of mother-to-child transmission of human immunodeficiency virus type 1.

OBJECTIVE: The purpose of this study was to evaluate the effect of elective cesarean delivery plus a lamivudine-zidovudine prophylaxis regimen on non-breastfeeding mothers with human immunodeficiency virus type 1 and their infants. STUDY DESIGN: Forty-six antiretroviral-naïve, pregnant women with human immunodeficiency virus type 1 were included. The prophylactic regimen was a lamivudine-zidovudine tablet (150 mg/300 mg) twice daily from week 34 of pregnancy until cesarean delivery at week 38 of gestation, preoperative intravenous zidovudine, and neonatal zidovudine syrup for 4 weeks. RESULTS: At weeks 34 and 38 of gestation, the median maternal viral loads were, respectively, 3.65 log(10) copies/mL (range, 2.34-4.70 log(10) copies/mL) and 2.51 log(10) copies/mL (range, 2.04-3.66 log(10) copies/mL; P<.001), respectively; the viral reduction was 1.12 log(10) copies/mL (range, -0.16-2.60 log(10) copies/mL), and the CD4(+) cell counts increased from 335 cells/mm(3) (range, 57-974 cells/mm(3)) to 420 cells/mm(3) (range, 84-1,083 cells/mm(3); P=.002). No mother or infant had a serious adverse event. Two infants were infected (4.3%; 95% CI, 0.5%-15.7%); 1 infant had intrapartum infection. CONCLUSION: Elective cesarean delivery plus short-course lamivudine-zidovudine is safe but does not eliminate mother-to-child transmission of human immunodeficiency virus type 1.

Prevalence of hepatitis B virus and hepatitis C virus co-infection with human immunodeficiency virus in Thai patients: a tertiary-care-based study.

BACKGROUND: Hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV share the route of transmission. HBV or HCV co-infection with HIV has been associated with a reduced survival rate, an increased risk of progression to severe liver disease, and an increased risk of hepatotoxicity associated with active antiretroviral therapy. Information regarding prevalence of HBV and HCV co-infection with HIV in Thailand is limited. PATIENTS AND METHOD: A cross-sectional study of prevalence and risk factors of HBV and HCV co-infection in HIV-infected patients was conducted. All HIV-infected patients who were cared for in March 2003 at Ramathibodi Hospital were included. RESULTS: There were 529 HIV-infected patients with a mean age of 36.7 years and 56.5% males. Of these, 58.8% lived in Bangkok, whereas, the others were from provincial areas. Heterosexual contact were the acquisition of HIV infection in 98.1% of all patients. The prevalence of HBV infection was 8.7%, and HCV infection was 7.8%. There was no difference between the prevalence of these infections in Bangkok and provincial areas (p = 0.115). History of intravenous drug use was associated with both HBV and HCV co-infection (p < 0.001). HCV co-infection group was also associated with male gender (p = 0.002) and elevated serum alanine transaminase (ALT) level (p = 0.0003). CONCLUSIONS: The prevalence of HBV and HCV co-infection with HIV in Thai patients is significant. In the author s resources-limited setting, history of intravenous drug use is a major indicator to screen for both HBV and HCV co-infection. Male gender and elevated serum ALT level are also suggestive of HCV co-infection.

Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial.

BACKGROUND: Scheduled treatment interruptions are being evaluated in an effort to decrease costs and side effects of highly active antiretroviral therapy (HAART). A schedule of 1 week on and 1 week off therapy offers the promise of 50% less drug exposure with continuously undetectable HIV RNA concentration. METHODS: In the Staccato study 600 patients on successful HAART were to be randomized to either continued therapy, CD4-guided therapy, or one week on, one week off therapy. A scheduled preliminary analysis evaluated effectiveness in the 1-week-on-1-week-off arm. RESULTS: Of 36 evaluable patients, 19 (53%) had two successive HIV RNA concentrations > 500 copies/ml at the end of the week off therapy, and were classified as virological failure. Most of those who failed took didanosine, stavudine, saquinavir, and ritonavir (11 patients). In these patients, there was no evidence of mutations suggestive of drug resistance, and plasma saquinavir levels were within the expected range. Two of three patients failing on triple nucleotides had drug resistance mutations, but nonetheless responded to reintroduction of triple nucleotide therapy. One of two patients taking nevirapine, and one of eight taking efavirenz, also failed. Both had resistance mutations at the time of failure, but not at baseline. CONCLUSIONS: The 1-week-on-1-week-off schedule, as tested in the Staccato study, showed an unacceptably high failure rate and was therefore terminated.

Ceftriaxone compared with sodium penicillin g for treatment of severe leptospirosis.

A prospective, open-label, randomized trial at Khon Kaen Hospital (Thailand) was conducted from July 2000 through December 2001 to compare the clinical efficacies of ceftriaxone and sodium penicillin G for the treatment of severe leptospirosis. A total of 173 patients with severe leptospirosis were randomly assigned to be treated with either intravenous ceftriaxone (1 g daily for 7 days; n=87) or intravenous sodium penicillin G (1.5 million U every 6 h for 7 days; n=86). The primary outcome was time to fever resolution. Survival analysis demonstrated that the median duration of fever was 3 days for both groups. Ten patients (5 in each group) died of leptospirosis infection. There were no statistically significant differences in the duration of organ dysfunction. Ceftriaxone and sodium penicillin G were equally effective for the treatment of severe leptospirosis. Once-daily administration and the extended spectrum of ceftriaxone against bacteria provide additional benefits over intravenous penicillin.