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BACKGROUND: Empiric therapy for community-acquired pneumonia (CAP) requires the use of antibiotics with activity against a broad spectrum of respiratory pathogens and suitable pharmacokinetic properties to simplify IV-to-oral step-down therapy switches. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of IV gatifloxacin with the option for oral stepdown gatifloxacin with a standard regimen of IV ceftriaxone (with or without erythromycin or clarithromycin) with the option for oral stepdown clarithromycin in patients with mild to moderate CAP requiring hospitalization. METHODS: In a randomized, open-label, parallel-group, multicenter study, adults with CAP received 7 to 14 days of treatment with either IV gatifloxacin 400 mg QD with the stepdown option or IV ceftriaxone 1 or 2 g QD (with or without erythromycin 0.5 or 1 g QID or clarithromycin 500 mg BID) with the stepdown option. RESULTS: One hundred seventy adults with CAP were included in the study. IV gatifloxacin was stepped down to oral gatifloxacin in 90.6% (7785) of patients; IV ceftriaxone was stepped down to oral clarithromycin in 87.1% (7485) of patients. Among clinically evaluable patients (n = 153), cure rates at 1 to 3 days after treatment were 97.4% in the gatifloxacin group (7476) and 90.9% in the ceftriaxone group (7077), with a 95% CI for the difference (-3.7% to 19.1%) indicating statistical equivalence. In patients in whom pathogens were isolated from pretreatment sputum cultures, bacteriologic eradication rates were 100.0% (2929) and 90.9% (3033), respectively. Both regimens were well tolerated; treatment-related adverse events occurred in 27.1% (2385) and 21.2% (1885) of patients, respectively. CONCLUSIONS: In the population studied, treatment with IV gatifloxacin with an option for oral stepdown gatifloxacin was as effective for achieving clinical cure as IV ceftriaxone (with or without concomitant IV erythromycin or clarithromycin) with an option for oral stepdown clarithromycin. Both regimens were well tolerated. [ABSTRACT FROM AUTHOR]

IgG molecules were found associated with erythrocyte membranes in all patients with American visceral leishmaniasis. They were detected by two different immunoradiometric assays and by one enzyme-linked immunosorbent assay. Although autoimmune phenomena seem to be constant features of American visceral leishmaniasis, the erythrocyte- bound IgG are not erythrocyte-specific autoantibodies. Moreover. anti-Leishmania activity was found associated with the erythrocyte-bound IgG. indicating that the IgG may be a component of Leishmania antigens-anti-Leishmania immune complexes. No associations were found between the amounts of erythrocyte-bound IgG and the degree of anaemia or between spleen dimensions and the degree of anaemia. These findings suggest that the pathogenesis of aneamia in American viscera' leshmaniasis is multifactorial. [ABSTRACT FROM AUTHOR]

It has been postulated that deficient or incomplete clinical and/or microbiological response to tuberculosis treatment is associated with cell-mediated immunological dysfunction involving monocytes and macrophages. A phase 2 safety trial was conducted by treating patients with either recombinant human granulocyte-macrophage colony-stimulating factor (rhu-GM-CSF) or a placebo, both in combination with anti-tuberculosis chemotherapy. Thirty-one patients with documented pulmonary tuberculosis were treated with rifampin/isoniazid for six months, plus pyrazinamide for the first two months. At the beginning of treatment, rhu-GM-CSF (125µg/M²) was randomly assigned to 16 patients and injected subcutaneously twice weekly for four weeks; the other 15 patients received a placebo. The patients were accompanied in the hospital for two weeks, then monthly on an out patient basis, for 12 months. Clinical outcomes were similar in both groups, with no difference in acid-fast bacilli (AFB) clearance in sputum at the end of the fourth week of treatment. Nevertheless, a trend to faster conversion to negative was observed in the rhu-GM-CSF group until the eighth week of treatment (p=0.07), after which all patients converted to AFB negative. Adverse events in the rhu-GM-CSF group were local skin inflammation and an increase in the leukocyte count after each injection, returning to normal 72 hours after rhu-GM-CSF injection. Three patients developed SGOP and SGPT > 2.5 times the normal values. All patients included in the GM-CSF group were culture negative at six months, except one who had primary TB resistance. None of the patients had to discontinue the treatment in either group. We conclude that rhu-GM-CSF adjuvant immunotherapy could be safely explored in a phase 3 trial with patients who have active tuberculosis.

Adherence is the milestone of a successful therapy. Over the last decade several authors have addressed the importance of adherence for optimal results of antiretroviral (ARV) therapy. Many health care systems are investing substantial resources to make available contemporary antiretroviral therapy. Despite the large investment in medications, insufficient investments have been made into an integrated adherence component to maximize the impact of these medications. Adherence, unlike drug therapy, cannot be defined as a single method with a defined prescription or formula. Instead, it is the result of a complex interaction between the patient, a prescribed medication and the health system. Many reports are available analyzing each of these components. We have found that critical elements of adherence include the patient's knowledge about the disease and how medications will help achieve a longer and healthier life, together with the motivation to adapt to a new style of life. A trilogy composed of information, motivation and behavioral skills is essential to achieve the maximum desired level of adherence. We have computerized this trilogy in a software program for self-administration in which each of the three components is provided to the patient as many times as necessary to transmit an understanding of the problem and to help make a rational decision to adhere to the ARV treatment program. In this review we analyze several efforts and techniques to improve adherence to any recommended medication that may interfere with the patient's lifestyle and outline how the adherence trilogy can be best used to optimize the ability of ARV therapy to durably suppress plasma HIV RNA to undetectable levels.

Post-kala-azar dermal leishmaniasis (PKDL) is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area) presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

The safety and efficacy of cefepime empiric monotherapy compared with standard broad-spectrum combination therapy for hospitalized adult patients with moderate to severe community-acquired bacterial infections were evaluated. In an open-label, multicenter study, 317 patients with an Acute Physiology and Chronic Health Evaluation (APACHE II) score ranging from >5 to =19 were enrolled with documented pneumonia (n=196), urinary tract infection (n=65), intra-abdominal infection (n=38), or sepsis (n=18). Patients were randomly assigned 1:1 to receive cefepime 1 to 2 g IV twice daily or three times a day or IV ampicillin, cephalothin, or ceftriaxone ± aminoglycoside therapy for 3 to 21 days. For both treatment groups, metronidazole, vancomycin, or macrolide therapy was added as deemed necessary. The primary efficacy variable was clinical response at the end of therapy. Two hundred ninety-six (93%) patients met evaluation criteria and were included in the efficacy analysis. Diagnoses included the following: 180 pneumonias (90 cefepime, 90 comparator), 62 urinary tract infections (29 cefepime, 33 comparator), 37 intra-abdominal infections (19 cefepime, 18 comparator), and 17 sepses (8 cefepime, 9 comparator). At the end of therapy, overall clinical success rates were 131/146 (90%) for patients treated with cefepime vs 125/150 (83%) for those treated with comparator (95% confidence interval [CI]: - 2.6% to 16.3%). The clinical success rate for patients with community-acquired pneumonia, the most frequent infection, was 86% for both treatment groups. Among the patients clinically evaluated, 162 pathogens were isolated and identified before therapy. The most commonly isolated pathogens were Escherichia coli (n=49), Streptococcus pneumoniae (n=29), Haemophilus influenzae (n=14), and Staphylococcus aureus (n=11). Bacteriologic eradication/presumed eradication was 97% for cefepime vs 94% for comparator-treated patients. Drug-related adverse events were reported in 16% of cefepime patients and 19% of comparator patients. In conclusion, cefepime had higher cure rates compared with broad-spectrum combination therapy as an initial empiric treatment for hospitalized patients with moderate to severe community-acquired infections, including urinary tract infections, intra-abdominal infections, and sepsis.

Post-kala-azar dermal leishmaniasis (PKDL) is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area) presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

We evaluated samples of peripheral blood mononuclear (PBMC) cells from 46 AIDS patients, before starting therapy with HIV-1 reverse transcriptase inhibitors (RTI), and after 6 months of drug use. PBMC were stored and tested by a Line Probe Assay (LiPA), in order to assess the frequency of RT mutations in this population. Six patients were taking AZT before initial blood collection (1 to 16 weeks of drug use) and 40 patients had no prior therapy. After baseline evaluation, 19 patients received AZT, 23 AZT plus DDI, 3 started AZT only with DDI added after 3 months, and 3 received a combination of AZT plus 3TC. Detection of at least one mutation was found in 33% (15/46) of patients at baseline, and 83% (38/46) had at least 1 mutation after 6 months of therapy. In the majority of cases, samples presented with the wild type and variants of HIV, simultaneously. Patients receiving monotherapy had a higher frequency of mutations (L41 and F214, Y215) than did patients receiving double-drug therapy (19 vs. 10). No specific mutation associated with DDI was identified in 26 patients so treated. Despite the finding of a mean increase in CD4 count and a mild decrease in viral load, patients tended to have an inverse correlation between the CD4 variation and number of mutations detected after 6 months, suggesting potential loss of drug efficacy in the presence of these genotypic changes.

Diarrhea due to intestinal microbial infections is a frequent manifestation among HIV-infected patients. It has been postulated that HIV-infected patients may have special types of intestinal infections, and that immune activation from such parasites may affect the progression of HIV disease. To evaluate these associations, the frequency of infections was examined in HIV-infected patients in Bahia, Brazil. To determine the potential impact of the presence of intestinal parasitic infections on HIV disease progression, a retrospective study approach was used. The medical charts of 365 HIV-infected patients who had been treated at the AIDS Clinic of the Federal University of Bahia Hospital were reviewed, and the prevalence of parasites was compared with 5,243 HIV-negative patients who had attended the hospital during the same period of time. Among HIV-infected subjects, CD4 count, RNA plasma viral load (VL), and number of eosinophils were compared according to their stool examination results. The overall prevalence of each parasite was similar for HIV-positive and HIV-negative patients. However, the prevalence of S. stercoralis (p

Immunotherapy has been proposed as a method to treat mucosal leishmaniasis for many years, but the approach has been hampered by poor definition and variability of antigens used, and results have been inconclusive. We report here a case of antimonial-refractory mucosal leishmaniasis in a 45 year old male who was treated with three single injections (one per month) with a cocktail of four Leishmania recombinant antigens selected after documented hypo-responsiveness of the patient to these antigens, plus 50mg of GM-CSF as vaccine adjuvant. Three months after treatment, all lesions had resolved completely and the patient remains without relapse after two years. Side effects of the treatment included only moderate erythema and induration at the injection site after the second and third injections. We conclude that carefully selected microbial antigens and cytokine adjuvant can be successful as immunotherapy for patients with antimonial-refractory mucosal leishmaniasis.