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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An open, randomized, multicentre clinical trial was conducted to compare the efficacy and safety of cefepime 2 g iv bd (2 g tds daily in cases of Pseudomonas aeruginosa pneumonia) with cefotaxime 2 g iv tds, in the empirical treatment of bacterial pneumonia in HIV-infected patients. The primary end-point was effectiveness after 3-5 days of treatment, taking success to be when the study drug was continued during this period of time. Clinical and bacteriological responses at end of treatment (EOT) were also evaluated. Analyses of the intention-to-treat population (n = 160) and the as-per-protocol groups (n = 150) were carried out. Treatment groups were comparable with regard to sex, age, HIV status and degree of severity of pneumonia. The primary end-point for cefepime was considered successful for the intention-to-treat and as-per-protocol groups in 85.7% and 93.5% of cases, respectively, and for cefotaxime, in 77.6% and 80.8% of cases, respectively (P = 0.22 and P = 0.02). In the as-per-protocol group, cefotaxime treatment was independently related to failure at the primary end-point. A satisfactory clinical response in the intention-to-treat population was observed in 83.3% of cefepime and 82.9% of cefotaxime patients. Bacteriological cure was obtained in 100% of evaluable cefepime and 93.4% of evaluable cefotaxime patients at EOT. Safety of the study drugs was comparable in both treatment groups. Cefepime 2 g iv bd was at least as effective and as well tolerated as cefotaxime 2 g iv tds in the treatment of bacterial pneumonia in HIV-infected patients.
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PMID:Cefepime versus cefotaxime for empirical treatment of bacterial pneumonia in HIV-infected patients: an open, randomized trial. 1158 Dec 32

Antimicrobial resistance is reaching epidemic proportions. Bacteria have developed an impressive array of defenses to protect themselves against potent compounds. The widespread emergence of resistance has complicated the treatment of infections due to Staphylococcus, Streptococcus, Enterococcus, Neisseria, Haemophilus, gram-negative enteric bacilli, and Pseudomonas. Multidrug-resistant tuberculosis poses a grave public health problem, particularly among the homeless and those infected with HIV. HIV resistance to nucleoside analogs such as zidovudine is increasingly common and seriously threatens their clinical usefulness. It is apparent that simply producing new drugs is not a viable solution to the resistance crisis. Rational use of existing antimicrobial agents is vital, and combination regimens must be intelligently deployed. State-of-the-art molecular epidemiology will aid in the detection, analysis, and termination of resistance epidemics. Control of drug-resistant Mycobacterium tuberculosis will require appropriate initial treatment regimens, proper therapeutic modification using the latest susceptibility testing methods, and strong emphasis on measures ensuring compliance. HIV resistance is a challenging problem, and novel strategies will be necessary to combat it. Recognition that drug resistance among bacteria and viruses is a rapidly growing threat worldwide is an important first step toward finding effective long-term solutions.
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PMID:Will the Nineties Be the Decade We Lost the Battle Against Drug-Resistant Microbes? 1183 84

OBJECTIVE: To assess the molecular epidemiology and risk factors for Pseudomonas aeruginosa colonization and infection in hospitalized patients. METHODS: In a 1000-bed university hospital, newly admitted patients were assessed prospectively for colonization and infection with P. aeruginosa. Anal swabs were obtained upon admission and at discharge. Ribotyping was used for the typing of isolates. Epidemiologic and clinical data were recorded prospectively. Independent risk factors were assessed using multivariate analysis. RESULTS: The recovery rate of patients with P. aeruginosa from anal specimens on admission was 6.7% (42/628). Infection due to P. aeruginosa was observed in 20 of 628 (3.2%) patients, of whom 10 (1.6%) were already infected on admission. Independent risk factors for colonization/infection on admission were age, indwelling urinary catheter, the presence of wound and seropositivity for HIV. Independent risk factors for nosocomial infection were anal colonization on admission, alcoholism, indwelling urinary catheter and antibiotic treatment during hospitalization. Ribotyping revealed that 27 patients were colonized or infected with a unique ribotype, whereas 24 shared one or more ribotypes with other patients. Analysis of epidemiologic and molecular typing data revealed that transmission from patients to patients or from patients to environment was documented on only three occasions. CONCLUSIONS: A great many P. aeruginosa strains were isolated from patients and the environment, and most environmental strains were different from those recovered in patients, suggesting a low rate of hospital acquisition of P. aeruginosa from the environment. The main risk factors for hospital-acquired infection were detectable colonization on admission, antibiotic treatment and urinary catheter.
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PMID:Frequency and molecular diversity of Pseudomonas aeruginosa upon admission and during hospitalization: a prospective epidemiologic study. 1186 38

Our knowledge of chronic suppurative otitis media is scanty in Ethiopia. This hospital-based study was, thus, conducted prospectively over a period of 2 years among children visiting a tertiary facility in Addis Ababa. Demographic, clinical, audiometric and microbiological data were collected using a preformed questionnaire. A total of 391 patients constituting 0.6% of the hospital patient population and 22.3% of those seen at the ear, nose, and throat clinic had chronic suppurative otitis media. Most (82.1%) of them were from Addis Ababa, the male to female ratio was 1.6:1, and their median age at presentation was 5.9 years. Otorrhoea had started before the age of 2 years in 269 (68.8%), was bilateral in 215 (55.0%), recurrent in 285 (72.9%), and continuous in 106 (27.1%). Otalgia was reported in only 18%. Hearing loss was the major presenting symptom and the loss was moderate to severe (grades 2 and 3) in 32 (69.6%) and slight (grade 1) in 14 (30.4%) of the ears tested audiometrically. Malnutrition, nasopharyngitis, measles, HIV infection, tuberculosis, diabetes mellitus, neoplastic diseases, and structural abnormalities were common antecedents. Serious complications included systemic infections, otogenic meningitis, mastoiditis, and tetanus. A total of 106 bacterial isolates were cultured from ear discharges of 80 patients. Proteus species were the commonest, accounting for 40 (37.7%) followed by Staphylococcus aureus, Pseudomonas aeruginosa, and Gram negative enterics. All isolates were highly resistant to the commonly used antibiotics including penicillin, ampicillin, amoxycillin, trimethoprim-sulfamethoxazole, and chloramphenicol. Augmentin, gentamicin, and kanamycin were the only drugs to which most of the pathogens were sensitive. Marked improvement on the discharge was achieved in 64% of the 116 patients who complied with treatment. Awareness about the health implications of the disease seemed to be lacking in among the caretakers. Selective use of antibiotics and continuous aural cleansing need to be promoted. More elaborate epidemiological studies will be required to define the magnitude of the problem and identify optimal therapeutic modalities of suppurative ear disease in Ethiopia.
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PMID:Chronic suppurative otitis media in a children's hospital in Addis Ababa, Ethiopia. 1196 74

Low-molecular-mass neutrophil elastase inhibitors have been shown to be important in the control of lung inflammation. In addition to inhibiting the enzyme neutrophil elastase, these low-molecular-mass compounds (10 kDa) have been shown to have other activities. For example, secretory leucocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor/SKALP (skin-derived antileucoproteinase)/elafin have also been shown to have "defensin"-like antimicrobial activities. Indeed, these inhibitors have antimicrobial properties in vitro against bacteria, fungi and, potentially, HIV. In addition, we have shown, using an adenovirus-mediated gene transfer overexpression strategy, that elafin is also active against Pseudomonas aeruginosa infection in mice in vivo. The mechanism of action is currently under investigation. In addition to these direct or indirect effects on microbes, it has been shown that lipopolysaccharide is able to up-regulate SPLI production in macrophages in vitro, and that the addition of recombinant SLPI to human monocytes or the transfection of macrophages with SPLI can down-regulate pro-inflammatory mediators such as tumour necrosis factor, presumably to limit self-damaging excessive inflammation. Using viral gene transfer vectors, we are currently investigating the potential of these inhibitors in various models of inflammation in vivo.
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PMID:Antimicrobial activity of antiproteinases. 1202 36

HIV-infected cells are selectively killed by an immunotoxin in which a truncated form of Pseudomonas exotoxin A is joined to the variable region of a broadly neutralizing antibody (3B3) that recognizes the viral envelope glycoprotein (Env). To improve the efficacy of this molecule, we used three-dimensional structural information and phage selection data to design 23 single and multiple point mutations in the antibody variable region sequences that contact Env. Substituting an aromatic residue for an aspartate in the third complementarity-determining region of V(H) increased the potency of the immunotoxin by approximately 10-fold in a cell-killing assay. Detailed analysis of one such mutant, N31H/Q100eY, revealed both a higher affinity for monomeric and cell surface Env and an increased stability against aggregation compared with the starting immunotoxin. Conversion to a disulfide-linked two-chain format further stabilized the protein. N31H/Q100eY retained the ability to bind to Env from multiple viral isolates, to inhibit Env-mediated cell fusion, and to limit spreading viral infection in peripheral blood mononuclear cells. Such site-directed mutants may increase the utility of immunotoxins for reducing or eradicating persistent HIV-1 infection in humans.
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PMID:Increased affinity and stability of an anti-HIV-1 envelope immunotoxin by structure-based mutagenesis. 1211

In human immunodeficiency virus (HIV)-infected patients, bacterial lower respiratory tract infections are the most frequent respiratory diseases. They are frequently the first clinical manifestation of HIV infection. The incidence and severity of bacterial lower respiratory tract infections increase with the degree of immunosuppression. At the acquired immune deficiency syndrome (AIDS) stage, the responsible bacteria and clinical presentation may be atypical. Bacterial pneumonia may be fatal, particularly in AIDS patients, and its occurrence is predictive of a reduced survival time. Pneumococcal vaccine is recommended in patients with a CD4 T-lymphocyte count of > 200 cells mm(-3) and cotrimoxazole (trimethoprim/sulfamethoxazole) in patients with a CD4 T-lymphocyte count of < 200 cells x mm(-3). Unfortunately, such prophylaxis remains insufficiently prescribed and its protective effect is limited. Highly active antiretroviral treatment has dramatically reduced the incidence of lower respiratory tract infection due to Pseudomonas aeruginosa and opportunistic bacteria. In contrast, successful highly active antiretroviral therapy slightly decreased the risk of bacterial pneumonia due to usual bacteria, even in patients on successful highly active antiretroviral therapy.
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PMID:Pyogenic bacterial lower respiratory tract infection in human immunodeficiency virus-infected patients. 1216 45

Cis-aminoindanol, a key chiral precursor to the HIV protease inhibitor CRIXIVAN, can be derived from indene oxidation products of (2R) stereochemistry. A number of different microorganisms, notably strains of the genera Pseudomonas and Rhodococcus, have been isolated that catalyze the oxygenation of indene to indandiol with greater stereospecificity than is achievable through traditional chemical synthesis. The yield and ultimate optical purity of indandiol produced in such biocatalytic processes is influenced by the intrinsic stereospecificity of the oxygenase(s), enantioselective dehydrogenation, and the loss of substrate to alternate, undesirable metabolites. Metabolic engineering of any indene bioconversion system for the commercial-scale production of cis-aminoindanol must account for these influences, as well as pathway fluxes and enzyme regulation, to optimize the formation of oxygenated precursors with useful stereochemistry. As such, the process by which bacterial systems carry out the bioconversion of indene to indandiol serves as a model for biological production of industrially relevant chiral synthons.
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PMID:Engineering an indene bioconversion process for the production of cis-aminoindanol: a model system for the production of chiral synthons. 1217 1

Stenotrophomonas maltophilia is an emerging nosocomial pathogen associated with opportunistic infections in patients with cystic fibrosis, cancer, and HIV. Adherence of this organism to abiotic surfaces such as medical implants and catheters represents a major risk for hospitalized patients. The adhesive surface factors involved in adherence of these bacteria are largely unknown, and their flagella have not yet been characterized biochemically and antigenically. We purified and characterized the flagella produced by S. maltophilia clinical strains. The flagella filaments are composed of a 38-kDa subunit, SM(FliC), and analysis of its N-terminal amino acid sequence showed considerable sequence identity to the flagellins of Serratia marcescens (78.6%), Escherichia coli, Proteus mirabilis, Shigella sonnei (71.4%), and Pseudomonas aeruginosa (57.2%). Ultrastructural analysis by scanning electron microscopy of bacteria adhering to plastic showed flagellalike structures within the bacterial clusters, suggesting that flagella are produced as the bacteria spread on the abiotic surface.
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PMID:Characterization of flagella produced by clinical strains of Stenotrophomonas maltophilia. 1219 67

The bionconversion of indene to cis-(1S,2R)-indandiol, a potential key intermediate in the synthesis of Merck's HIV protease inhibitor, CRIXIVAN trade mark, can be achieved using Rhodococcus, Pseudomonas putida, and Escherichia coli strains. This study reports on the application of multiparameter flow cytometry for the measurement of cytoplasmic membrane integrity and membrane depolarization as indicators of toxic effects of the substrate, product, and by-products using each of these strains. Measurements of oxygen uptake rate (OUR) and optical density (OD) as indicators of metabolic activity and biomass growth, respectively, were also made. Measurements of the cytoplasmic membrane potential, cell viability, and respiratory activity provided a sensitive set of parameters to assess toxicity in the indene bioconversion and provided the basis for process improvements and strain selection. The toxic concentrations of the substrate, product, and by-products for each strain have been determined. The results show that it is possible to accumulate cis-(1S,2R)-indandiol and cis-1-amino-2-indanol up to 20 g/L without significant negative effects on cell physiology using any of the strains tested. The Gram-negative P. putida (421-5 and GM 730) and E. coli strains were more resistant to indene and the isolated chemicals of the biotransformation than the Gram-positive Rhodoccoccus I24 strain, possibly due to the presence of the outer membrane and efflux pump mechanisms. P. putida GM 730 and the E. coli TDO 123 strains responded similarly to toxic effects, and the E. coli TDO 123 strain was more resistant than the P. putida 421-5 strain. In addition to the recommendations for strain selection, the identified targets for bioprocess improvement include a combination of genetic as well as process engineering approaches.
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PMID:Measurement of strain-dependent toxicity in the indene bioconversion using multiparameter flow cytometry. 1249 26


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