Does HIV status affect the aetiology, bacterial resistance patterns and recommended empiric antibiotic treatment in adult patients with bloodstream infection in Cambodia?

OBJECTIVE: The microbiologic causes of bloodstream infections (BSI) may differ between HIV-positive and HIV-negative patients and direct initial empiric antibiotic treatment (i.e. treatment before culture results are available). We retrospectively assessed community-acquired BSI episodes in adults in Cambodia according to HIV status for spectrum of bacterial pathogens, antibiotic resistance patterns and appropriateness of empiric antibiotics. METHODS: Blood cultures were systematically performed in patients suspected of BSI in a referral hospital in Phnom Penh, Cambodia. Data were collected between 1 January 2009 and 31 December 2011. RESULTS: A total of 452 culture-confirmed episodes of BSI were recorded in 435 patients, of whom 17.9% and 82.1% were HIV-positive and HIV-negative, respectively. Escherichia coli accounted for one-third (n = 155, 32.9%) of 471 organisms, with similar rates in both patient groups. Staphylococcus aureus and Salmonella cholereasuis were more frequent in HIV-positive vs. HIV-negative patients (17/88 vs. 38/383 (P = 0.02) and 10/88 vs. 5/383 (P < 0.001)). Burkholderia pseudomallei was more common in HIV-negative than in HIV-positive patients (39/383 vs. 2/88, P < 0.001). High resistance rates among commonly used antibiotics were observed, including 46.6% ceftriaxone resistance among E. coli isolates. Empiric antibiotic treatments were similarly appropriate in both patient groups but did not cover antibiotic-resistant E. coli (both patient groups), S. aureus (both groups) and B. pseudomallei (HIV-negative patients). CONCLUSION: The present data do not warrant different empiric antibiotic regimens for HIV-positive vs. HIV-negative patients in Cambodia. The overall resistance rates compromise the appropriateness of the current treatment guidelines.

Vitamin D rescues impaired Mycobacterium tuberculosis-mediated tumor necrosis factor release in macrophages of HIV-seropositive individuals through an enhanced Toll-like receptor signaling pathway in vitro.

Mycobacterium tuberculosis disease represents an enormous global health problem, with exceptionally high morbidity and mortality in HIV-seropositive (HIV(+)) persons. Alveolar macrophages from HIV(+) persons demonstrate specific and targeted impairment of critical host cell responses, including impaired M. tuberculosis-mediated tumor necrosis factor (TNF) release and macrophage apoptosis. Vitamin D may promote anti-M. tuberculosis responses through upregulation of macrophage NO, NADPH oxidase, cathelicidin, and autophagy mechanisms, but whether vitamin D promotes anti-M. tuberculosis mechanisms in HIV(+) macrophages is not known. In the current study, human macrophages exposed to M. tuberculosis demonstrated robust release of TNF, IκB degradation, and NF-κB nuclear translocation, and these responses were independent of vitamin D pretreatment. In marked contrast, HIV(+) U1 human macrophages exposed to M. tuberculosis demonstrated very low TNF release and no significant IκB degradation or NF-κB nuclear translocation, whereas vitamin D pretreatment restored these critical responses. The vitamin D-mediated restored responses were dependent in part on macrophage CD14 expression. Importantly, similar response patterns were observed with clinically relevant human alveolar macrophages from healthy individuals and asymptomatic HIV(+) persons at high clinical risk of M. tuberculosis infection. Taken together with the observation that local bronchoalveolar lavage fluid (BALF) levels of vitamin D are severely deficient in HIV(+) persons, the data from this study demonstrate that exogenous vitamin D can selectively rescue impaired critical innate immune responses in vitro in alveolar macrophages from HIV(+) persons at risk for M. tuberculosis disease, supporting a potential role for exogenous vitamin D as a therapeutic adjuvant in M. tuberculosis infection in HIV(+) persons.

Lactic acid bacteria population in children diagnosed with human immunodeficiency virus.

AIM: To determine the effect of trimethoprim/sulphamethoxazole treatment on the natural population of lactic acid bacteria in the intestinal tract and to determine if any of the strains developed resistance to antibiotics. METHODS: Lactic acid bacteria were isolated from stool samples of 100 children. The isolates were identified based on biochemical characteristics and DNA profiles obtained from polymerase chain reaction with genus- and species-specific primers. Resistance to sulphamethoxazole, streptomycin, compound sulphonamides, chloramphenicol and vancomycin was tested using the paper-disk method. RESULTS: The lactic acid bacteria were identified as Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus paracasei, Lactobacillus pentosus, Lactobacillus rhamnosus, Leuconostoc mesenteroides subsp. mesenteroides, Enterococcus spp. and Weissella spp. Lactobacillus plantarum and Bifidobacterium spp. were not isolated. All strains, except two, were sensitive to chloramphenicol and streptomycin. Thirty-five percent of the isolates were resistant to vancomycin, 50% to compound sulphonamides and 66% to sulphamethoxazole. CONCLUSION: Treatment with trimethoprim/sulphamethoxazole repressed a large number of lactic acid bacteria normally present in the intestinal tract of children. A number of strains were resistant to sulphamethoxazole and may be used as probiotics to correct the imbalance in lactic acid bacteria.

Fluconazole and amphotericin B susceptibility testing of Cryptococcus neoformans: results of minimal inhibitory concentrations against 265 isolates from HIV-positive patients before and after two or more months of antifungal therapy.

Cryptococcosis, a fatal disease without appropriate treatment, is still one of the major opportunistic mycoses in AIDS patients in Argentina despite the availability of high active anti-retroviral therapy (HAART). Over the last decade, drugs employed in the treatment of disseminated cryptococcosis at Infectious Diseases Hospital "F.J. Muñiz" included amphotericin B (AMB) followed by fluconazole (FCZ), due to the fact that flucytosine was not available in Argentina during this period. A considerable number of patients did not negativize cultures after 2-3 weeks of treatment as it was expected, and in some of them the isolation of Cryptococcus neoformans in different samples was still possible after 2 or more months of adequate therapy and even in cases with clinical improvement. The aim of this study was to establish the susceptibility profile of C. neoformans clinical isolates to those antifungals and to investigate whether there were any changes after at least 2 months of treatment. A total of 265 strains were studied (116 obtained from patients at diagnosis and 149 corresponding to the same individuals 2 months or more after receiving therapy). Susceptibility patterns before treatment to AMB showed MICs < or =1 microg/ml for all the strains, and no increase was seen after treatment. All the strains were susceptible to FCZ (MIC< or =8 microg/ml) at diagnosis; but in a group with relapses or those who did not negativize cultures, one isolate became resistant after therapy (MIC> or =64 microg/ml) and other four showed dose-dependent susceptibility (MIC 16-32 microg/ml). There was no relation between these results and clinical outcome as it was pointed out in other publications.

[No obvious difference in Streptococcus pneumoniae antibiotic resistance profiles--isolates from HIV-positive and HIV-negative patients]. / Vergleichbare Antibiotikaresistenz von Pneumokokkenisolaten HIV-positiver und -negativer Patienten.

BACKGROUND AND PURPOSE: HIV patients are overexposed to hospital environment, immune suppression, and antibiotic prophylaxes. Therefore, with HIV positive patients an increased risk for resistant bacterial rods is to be expected. The purpose of this case-control study was to determine the susceptibility patterns of pneumococci from adult patients in relation to their HIV status and to compare both patient groups. PATIENTS AND METHODS: Between January 2001 and December 2005, samples from internal medicine patients of one university hospital laboratory were investigated on culture of Streptococcus pneumoniae and in case of a positive vial, a resistance test was done by agar diffusion method. All patients with culture-confirmed infection due to pneumococci underwent a standardized retrospective evaluation in regard to demographic and clinical characteristics including HIV status. RESULTS: A total amount of 135 Streptococcus pneumoniae cultures could be assigned to 64 HIV-positive (A) and 71 HIV-negative patients (B), with susceptibility results for 134 isolates. Full susceptibility was seen in 44 (69.8% [A]) versus 42 (59.2% [B]) samples, reduced susceptibility ("intermediate-susceptible") was found in eight (12.7% [A]) versus 17 (23.9% [B]). Eleven (17.5% [A]) and twelve (16.9% [B]), respectively, out of all pneumococci were tested resistant to at least one antibiotic. Among these, resistance to erythromycin was most relevant (11.1% [A] and 11.3% [B]). None of the tested rods was resistant to penicillin. All differences between groups for susceptibility testing were not found significant. HIV-negative patients were significantly older, needed more often hospitalization and intensive care, and cultures for pneumococci were more frequently positive in primary sterile materials, such as cerebrospinal fluid and blood. The difference concerning death within 28 days following positive sample was just not significant as well as in immune suppression status of patients. HIV patients experienced more frequently an infection relapse and were more frequently smokers. CONCLUSION: No obvious difference in pneumococci resistance patterns was observed between HIV-positive and HIV-negative adult patients. The absence of resistance to penicillin underscores the importance of beta-lactams in case of typical community-acquired pneumonia; therefore, this class of antibiotics should be included in treatment guidelines as first-line drugs also for HIV patients. HIV-negative controls of this study were more aged and suffered from a higher morbidity, however, the fact that they were not significantly less immune suppressed may be special character of a university hospital control patient group. HIV patients presented in an earlier stage of their pneumococcal disease, probably due to a direct access to tertiary hospital medical supply. A higher relapse rate underscores the importance of pneumococcal vaccination for HIV patients.

Effect of commercial ethanol propolis extract on the in vitro growth of Candida albicans collected from HIV-seropositive and HIV-seronegative Brazilian patients with oral candidiasis.

The present study assessed the susceptibility of Candida albicans strains, collected from HIV-positive patients with oral candidiasis, to a commercial 20% ethanol propolis extract (EPE) and compare it to the inhibitory action of the standardized antifungal agents nystatin (NYS), clotrimazole (CL), econazole (EC), and fluconazole (FL). Twelve C. albicans strains collected from HIV-positive patients with oral candidiasis were tested. The inhibition zones were measured with a pachimeter and the results are reported as means and standard deviation (M +/- SD). Data were analyzed statistically by the non-parametric Kruskal-Wallis test. EPE inhibited all the C. albicans strained tested. No significant difference was observed between the results obtained with NYS and EPE, while significant differences were observed between EPE and other antifungals. The C. albicans strains tested showed resistance to the remaining antifungal agents. The propolis extract used in this study inhibited the in vitro growth of C. albicans collected from HIV-seropositive Brazilian patients, creating/forming inhibition zones like those ones formed by NYS. This fact suggests that commercial EPE could be an alternative medicine in the treatment of candidiasis from HIV-positive patients. However, in vivo studies of the effect of EPE are needed to determine its possible effects on the oral mucosa.

A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients.

OBJECTIVE: A systematic review of randomized clinical trials published between 1966 and April 2000 was undertaken to determine the strength of evidence for the effectiveness of antifungal drugs (nystatin, clotrimazole, amphotericin B, fluconazole, ketoconazole, and itraconazole) to prevent and treat oral candidiasis in human immunodeficiency virus-positive patients. STUDY DESIGN: An automated database search identified 366 articles. Six met inclusion and exclusion criteria with respect to prophylaxis; 12 met criteria for treatment of oral candidiasis. RESULTS: The evidence for the prophylactic efficacy of fluconazole is good, although insufficient to draw conclusions about the other antifungals. Evidence for treatment effectiveness is insufficient for amphotericin B but good for nystatin, clotrimazole, fluconazole, ketoconazole, and itraconazole. CONCLUSION: Suggestions for strengthening the evidence base include the following: use of larger, more well-defined groups; control for immunologic status, viral load, history of oral candidiasis, past exposure to antifungals, baseline oral Candida carriage, drug interactions, and antiretroviral therapy; and consistent use of compliance monitors, fungal speciation, and susceptibility testing.

[Genotype, serotype and sensitivity to fluconazole of Candida albicans strains isolated from HIV-positive patients]. / Génotype, sérotype et sensibilité au fluconazole de souches de Candida albicans isolées chez des patients VIH positif.

Genotype, serotype and susceptibility in vitro to fluconazole of 104 C. albicans strains isolated from HIV+ patients were studied. The possible correlations between genotype analysed by multilocus enzyme electrophoresis (MLEE) and phenotype of medical relevance (serotype and susceptibility to fluconazole) of Candida albicans isolated from these patients treated with fluconazole were evaluated by factorial correspondence analysis. No correlation was observed between genotype and in vitro or clinical response to fluconazole. In counterpart, serotype B C. albicans was associated with some multilocus genotypic patterns.

Detection of human immunodeficiency virus type 1 (HIV-1) proviral DNA in breast milk and colostrum of seropositive mothers.

There is increasing evidence of vertical transmission of HIV-1 to infants through breast feeding of milk from HIV-1 infected mothers. It has been postulated that transmission occurs mainly via ingestion of infected cells in breast milk and colostrum. In this study, detection of HIV-1 proviral DNA was used to prove that cells from colostrum and milk do contain HIV. DNA were extracted from these cells of colostrum and milk of 18 seropositive mothers and amplified by nested PCR for HIV-1 gag and pol and 44 per cent were positive mostly by two primers. All ten negative control samples from seronegative mothers were negative. This study demonstrated the infectivity of breast milk and colostrum. Nevertheless, recommendation against breast-feeding should be weighed against poor alternatives in low socioeconomic families.

PIP: In Thailand clinicians gathered breast milk and colostrum samples (1 ml) at 1-10 days postpartum from 18 HIV-1 seropositive mothers at Ramathibodi Hospital and Maharaj Hospital and from 10 HIV-1 seronegative mothers at the same hospitals. Researchers used polymerase chain reaction to detect HIV-1 proviral DNA in cells in the breast milk and colostrum. Breast milk and colostrum samples from 44% of the HIV-1 seropositive women tested positive for HIV-1 DNA. The pol primers were superior to the gag primers. All of the colostrum samples of the HIV-1 seronegative women tested negative. These results suggest that HIV-1 seropositive lactating mothers can transmit HIV-1 via breast feeding after childbirth. The Obstetrics and Gynaecology Department at Ramathibodi Hospital in Bangkok advises HIV-1 infected mothers to not breast feed if there is a suitable alternative available. Health professionals should weigh breast feeding against poor alternatives in impoverished families.

Detection of HIV-1 genome in leukocytes of human colostrum from anti-HIV-1 seropositive mothers.

In order to obtain more information about the presence of HIV-1 in mononuclear cells of colostrum, research was carried out on both the HIV-1 genome in the cellular fraction of colostrum and the viral antibody in cell-free colostrum of eight anti-HIV-1 seropositive asymptomatic mothers. In five cases cell fractions of the colostrum harbored HIV-1 genome by DNA-DNA and DNA-RNA in situ hybridization, whereas viral antibody were detected in all cell-free colostrum specimens. The data confirms the colostrum as a possible route of HIV-1 infection.

Rheumatological lesions in individuals with human immunodeficiency virus infection.

One hundred and twenty-three patients with human immunodeficiency virus infection have been referred to rheumatologists at our hospitals between October 1985 and April 1989 because of musculoskeletal symptoms. Thirty-four homosexual men presented with acute, peripheral, non-erosive arthritis (mean number of four joints affected) with the knees being involved in 23. Other features developing concurrently with arthritis included psoriasis, keratoderma blenorrhagica, plantar fasciitis, urethritis, conjunctivitis and anterior uveitis. Four of five patients investigated were HLA-B27-positive; none of 15 patients tested had raised titres of rheumatoid or antinuclear factors. Various infections were associated with the onset of arthritis and two patients with a recent history of diarrhoea had serological evidence of yersinia infection. No micro-organisms were identified within the joint except for HIV itself. At the time of onset of arthritis four of these individuals had the acquired immunodeficiency syndrome (AIDS); 11 were not known to be HIV-positive before testing which was performed following referral for arthritis. Six patients have since developed AIDS and four have died. In 15 individuals, including those who progressed to AIDS, joint symptoms have been severe, persistent and poorly responsive to non-steroidal anti-inflammatory drugs. In only five patients has the arthritis been known to resolve. Synovitis has also been seen in two women: in one of these HIV infection was thought to have been acquired through intravenous drug abuse. Other rheumatic lesions included myalgia/myositis, non-inflammatory peripheral arthritis, spinal pain, soft tissue lesions, arthralgia or myalgia of unknown cause and infective lesions including septic arthritis and bony infection due to histoplasmosis and atypical mycobacterial infection. It appears likely that HIV infection is a risk factor for the development of seronegative arthritis and other rheumatic lesions.