Prolonged Outbreak of Carbapenem and Colistin-Resistant Klebsiella pneumoniae at a Large Tertiary Hospital in Brazil.

Multidrug-resistant gram-negative bacteria, such as carbapenem and colistin-resistant Klebsiella pneumoniae (ColR-CRKP), represent a major problem for health systems worldwide and have high lethality. This study investigated the genetic relationship, antimicrobial susceptibility profile, and resistance mechanisms to ColR-CRKP isolates from patients infected/colonized in a tertiary hospital in Salvador, Bahia/Brazil. From September 2016 to January 2018, 46 patients (56 ColR-CRKP positive cultures) were enrolled in the investigation but clinical and demographic data were obtained from 31 patients. Most of them were men (67.7%) and elderly (median age of 62 years old), and the median Charlson score was 3. The main comorbidities were systemic arterial hypertension (38.7%), diabetes (32.2%), and cerebrovascular disease (25.8%). The average hospitalization stay until ColR-CRKP identification in days were 35.12. A total of 90.6% used mechanical ventilation and 93.7% used a central venous catheter. Of the 31 patients who had the data evaluated, 12 had ColR-CRKP infection, and seven died (58.4%). Previous use of polymyxins was identified in 32.2% of the cases, and carbapenems were identified in 70.9%. The minimum inhibitory concentration (MIC) for colistin was > 16 µg/mL, with more than half of the isolates (55%) having a MIC of 256 µg/mL. The bla KPC gene was detected in 94.7% of the isolates, bla NDM in 16.0%, and bla GES in 1.7%. The bla OXA-48, bla VIM, and bla IMP genes were not detected. The mcr-1 test was negative in all 56 isolates. Alteration of the mgrB gene was detected in 87.5% (n = 49/56) of the isolates, and of these, 49.0% (24/49) had alteration in size probably due to IS903B, 22.4% (11/49) did not have the mgrB gene detected, 20.4% (10/49) presented the IS903B, 6.1% (3/49) had a premature stop codon (Q30*), and 2.1% (1/49) presented a thymine deletion at position 104 - 104delT (F35fs). The PFGE profile showed a monoclonal profile in 84.7% of the isolates in different hospital sectors, with ST11 (CC-258) being the most frequent sequence type. This study presents a prolonged outbreak of ColR-CRKP in which 83.9% of the isolates belonged to the same cluster, and 67.6% of the patients evaluated had not used polymyxin, suggesting the possibility of cross-transmission of ColR-CRKP isolates.

Infection by HTLV-1 Is Associated With High Levels of Proinflammatory Cytokines in HIV-HCV-Coinfected Patients.

OBJECTIVES: HIV, hepatitis C virus (HCV), and human T-cell lymphotropic virus type 1 (HTLV-1) share the same routes of infection, making coinfection by these viruses a frequent finding in endemic areas. However, there is scarce information on the clinical/immunological consequences of triple infection. Coinfection by HTLV-1 is able to modulate cytokine's production in patients with HIV, but there are no data on the immune response of HIV-HCV-HTLV-1-infected patients. METHODS: We compared the plasma levels of 25 different cytokines in patients with HIV-HCV, according to their serostatus to HTLV-1 infection. Eligible patients should be on stable highly active antiretroviral therapy and have undetectable HIV-1 plasma viral load for, at least, 12 months. Cytokines levels were also evaluated by CD4 cells count, rates of sustained virological response (SVR) to previous HCV treatment, frequency of spontaneous HCV clearance, and HCV/IFN-λ3 genotypes. RESULTS: Twenty-five patients (15 coinfected by HIV and HCV, 10 coinfected by HIV, HCV, and HTLV-1) were evaluated. Among the triply infected group, 3 had undetectable HCV viremia (spontaneous clearance). All but one remaining patients were previously treated for HCV, with similar SVR rates (∼29%). Cytokines levels did not differ per HCV/IFN-λ3 genotypes, mean CD4 cells count, age, sex, or SVR. However, patients coinfected by HTLV-1 showed significantly higher levels of IL-1b, IL-2, TNF-α, IFN-γ, MIP-1α, RANTES, and interferon-induced protein 10 (IP-10) than HIV-HCV-coinfected ones. Patients presenting HCV spontaneous clearance had the highest levels of cytokines. CONCLUSIONS: Coinfection by HTLV-1 increases the plasma levels of proinflammatory cytokines of patients with HIV-HCV and can influence the outcomes of coinfected patients.

Hepatitis C virus infection and spontaneous clearance in HTLV-1 and HIV co-infected patients in Salvador, Bahia, Brazil

ABSTRACTBACKGROUND: While 20-40% of patients with hepatitis C virus (HCV) monoinfection will spontaneously clear the virus, less is known regarding clearance with coinfections. HCV, human immunodeficiency virus (HIV), and human T-cell lymphotrophic virus 1 and 2 (HTLV-1/2) coinfection occurs due to shared routes of transmission and is prevalent in Brazil.OBJECTIVES:To compare the proportion of patients who have spontaneously cleared HCV in patients with HCV monoinfection to patients coinfected by HCV/HIV, or HCV/HIV/HTLV-1.METHODS:Using medical records from two clinics in Salvador, Brazil, including demographic data and serological markers of HCV, HIV and HTLV-I/II, cross-sectional data was obtained from 197 patients. Patients who were anti-HCV positive and HCV RNA negative, and who did not receive HCV treatment were defined as having cleared infection.RESULTS:Nineteen patients (9.5%) showed evidence of spontaneous HCV clearance; with clearance in 9 of 108 (8.3%) patients in the HCV monoinfected group, 5 of 68 (7.4%) patients with HCV/HIV, and 5 of 21 (23.8%) patients with HCV/HIV/HTLV. Demographic data were not associated with HCV clearance status. Patients coinfected with both HIV and HTLV-1 had increased odds (5.50; 95% CI 1.00, 30.17) of spontaneous clearance of HCV compared with patients who were HIV negative or of unknown HIV status.CONCLUSION:Our study found that patients coinfected with HIV and HTLV-1 were more likely to spontaneously clear hepatitis C virus than patients with HIV/HCV or HCV alone. The effects of HTLV coinfection on the immune response of such patients may be associated with these findings.

Hepatitis C virus infection and spontaneous clearance in HTLV-1 and HIV co-infected patients in Salvador, Bahia, Brazil.

BACKGROUND: While 20-40% of patients with hepatitis C virus (HCV) monoinfection will spontaneously clear the virus, less is known regarding clearance with coinfections. HCV, human immunodeficiency virus (HIV), and human T-cell lymphotrophic virus 1 and 2 (HTLV-1/2) coinfection occurs due to shared routes of transmission and is prevalent in Brazil. OBJECTIVES: To compare the proportion of patients who have spontaneously cleared HCV in patients with HCV monoinfection to patients coinfected by HCV/HIV, or HCV/HIV/HTLV-1. METHODS: Using medical records from two clinics in Salvador, Brazil, including demographic data and serological markers of HCV, HIV and HTLV-I/II, cross-sectional data was obtained from 197 patients. Patients who were anti-HCV positive and HCV RNA negative, and who did not receive HCV treatment were defined as having cleared infection. RESULTS: Nineteen patients (9.5%) showed evidence of spontaneous HCV clearance; with clearance in 9 of 108 (8.3%) patients in the HCV monoinfected group, 5 of 68 (7.4%) patients with HCV/HIV, and 5 of 21 (23.8%) patients with HCV/HIV/HTLV. Demographic data were not associated with HCV clearance status. Patients coinfected with both HIV and HTLV-1 had increased odds (5.50; 95% CI 1.00, 30.17) of spontaneous clearance of HCV compared with patients who were HIV negative or of unknown HIV status. CONCLUSION: Our study found that patients coinfected with HIV and HTLV-1 were more likely to spontaneously clear hepatitis C virus than patients with HIV/HCV or HCV alone. The effects of HTLV coinfection on the immune response of such patients may be associated with these findings.

The impact of human T-cell lymphotropic virus I infection on clinical and immunologic outcomes in patients coinfected with HIV and hepatitis C virus.

BACKGROUND: HIV, hepatitis C (HCV), and human T-cell lymphotropic virus I (HTLV-1) are associated with high global burdens of disease, notably in resource-poor locales. They share similar routes of transmission and cause chronic infections with associated morbidity. We performed a cross-sectional study to assess the impact of HTLV-1 infection on clinical outcomes in HIV/HCV-coinfected patients. METHODS: We enrolled 102 (72.3%) with HIV/HCV coinfection (Group 1) and 39 (27.7%) triply infected with HIV, HCV, and HTLV-1 (Group 2). We reviewed medical records of two groups of patients followed in two outpatients services in Salvador, Brazil. We collected and compared demographic, behavioral-related information, immunologic, virologic, and histologic parameters for HIV-1 and HCV infection. RESULTS: Demographics, virologic, and immunologic characteristics were similar in the two groups; a higher proportion of triply infected patients (Group 2) reported any history of injection drug use compared with dually infected (Group 1) patients (75% vs 45.8%; P = 0.003). No differences were seen between groups in HIV clinical outcomes (CD4 count and viral load). Alanine aminotransferase levels were significantly higher in HIV/HCV-coinfected patients (P = 0.045). Liver fibrosis damage based on Metavir scores was similar between groups (0.97) but was worse with lower CD4 cell count (under 200 cells/mm) (P = 0.01). CONCLUSIONS: HIV/HTLV-1 and HIV/HCV coinfections may worsen clinical related outcomes, but virologic and immunologic outcomes were similar in both groups. Hepatic measures were worse in patients with more severe immunosuppression.

Evaluation of the genotypic pattern of HIV-1 resistance in AIDS patients failing antiretroviral therapy.

We analyzed the first 96 patients tested for HIV resistance to antiretroviral therapy in three Brazilian states. The HIV-1 reverse transcriptase (RT) and protease (PR) were sequenced by using the ABI ViroSeq system. The drugs previously used for each patient were recorded and correlated with the mutations found in the samples. Viral load (VL) and CD4 count were also recorded. Only one patient had the wild type sequence. The most prevalent mutations were: 184V (59%), 41L (47.9%), 63P (53%), 215Y (50%), 36I (46%), 10I (35%), 67N (42%), 77I (37%), 90M (36%) and 210W (33%). A positive correlation between the number of previously used ARVs and the number of mutations was observed (p<0.05). Associations between mutations and ARV drugs were identified at positions 69, 118, 184 and 215 with previous exposure to NRTI, mutations at positions 98, 100, 103, 181 and 190 with previous NNRTI use and at positions 10, 20, 30, 46, 53, 54, 71, 73, 82, 84, 88 and 90 with previous PI therapy (p<0.05). Previous exposure to ARV drugs was associated with previous genotypic resistance to specific drugs, leading to treatment failure in HIV patients. Genotypic resistance was clearly associated with virological and immunological failure.

Evaluation of the genotypic pattern of HIV-1 resistance in AIDS patients failing antiretroviral therapy

We analyzed the first 96 patients tested for HIV resistance to antiretroviral therapy in three Brazilian states. The HIV-1 reverse transcriptase (RT) and protease (PR) were sequenced by using the ABI ViroSeq system. The drugs previously used for each patient were recorded and correlated with the mutations found in the samples. Viral load (VL) and CD4 count were also recorded. Only one patient had the wild type sequence. The most prevalent mutations were: 184V (59 percent), 41L (47.9 percent), 63P (53 percent), 215Y (50 percent), 36I (46 percent), 10I (35 percent), 67N (42 percent), 77I (37 percent), 90M (36 percent) and 210W (33 percent). A positive correlation between the number of previously used ARVs and the number of mutations was observed (p<0.05). Associations between mutations and ARV drugs were identified at positions 69, 118, 184 and 215 with previous exposure to NRTI, mutations at positions 98, 100, 103, 181 and 190 with previous NNRTI use and at positions 10, 20, 30, 46, 53, 54, 71, 73, 82, 84, 88 and 90 with previous PI therapy (p<0.05). Previous exposure to ARV drugs was associated with previous genotypic resistance to specific drugs, leading to treatment failure in HIV patients. Genotypic resistance was clearly associated with virological and immunological failure.

A randomized, pilot trial comparing full versus escalating dose regimens for the desensitization of AIDS patients allergic to sulfonamides

Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective); alternatively attempts are made to desensitize the patient. OBJECTIVE: Compare two drug regimens (full vs. escalating doses) for the oral desensitization of AIDS patients allergic to sulfonamides. MATERIAL AND METHODS: AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL) and CD4/CD8 counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months. RESULTS: Eighteen patients were enrolled in the study (15 men and 3 women), with ages ranging from 30 to 57 years (mean 39.9). The mean CD4 counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD8 counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40 percent) in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed. CONCLUSON: Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with sulfonamides after an initial allergic reaction.

A randomized, pilot trial comparing full versus escalating dose regimens for the desensitization of AIDS patients allergic to sulfonamides.

UNLABELLED: Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective); alternatively attempts are made to desensitize the patient. OBJECTIVE: Compare two drug regimens (full vs. escalating doses) for the oral desensitization of AIDS patients allergic to sulfonamides. MATERIAL AND METHODS: AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75 mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL) and CD(4)/CD(8) counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months. RESULTS: Eighteen patients were enrolled in the study (15 men and 3 women), with ages ranging from 30 to 57 years (mean 39.9). The mean CD(4) counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD(8) counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40%) in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed. CONCLUSION: Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with sulfonamides after an initial allergic reaction.

Evaluation of viral resistance to reverse transcriptase inhibitors (RTI) in HIVB-1-infected patients before and after 6 moths of single or double antiretroviral therapy

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 lest one mutation was found in 33 percent (15/46) of patients at baseline, and 83 percent (38/46) had at least 1 mutation after 6 months of therapy. In the majority of cases, samples presented with the wild type and variats of HIV, simultaneously. Patients receiving monotherapy had a higher frequency of mutations (L41 and F214, Y215)than did patients receiving double-drug therapy (19vs.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.

Human herpes virus 8 and kaposi's sarcoma: A review

Kaposi's Sarcoma (KS) was first described one century ago as a disease occurring in elderly men manifested as an indolent cutaneous form. After the onset of human immunodeficiency virus type I (HIV-1) infection, KS became epidemic which, in association with HIV, presented as an aggressive, systemic disease. Recently, the recognition that a novel human herpes virus-8 (HHV-8) was highly prevalent among KS patients provided strong evidence to indicate that HHV-8 was the etiology of KS. The pathogenesis of KS in AIDS patients is still controversial, but there is evidence suggesting that KS is a cytokine-mediated disease, and that increased levels of inflammatory cytokines in AIDS patients were responsible for the aggressive pattern of disease seen in such patients. The recently developed serological assays for detection of HHV-8 antibodies have made possible a better understanding of the prevalence of HHV-8 in different populations, and this has allowed a deeper understanding of HIV-8 epidemiology.