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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The available data suggest that selected patients with tuberculosis and MAC fail to respond to therapy because they malabsorb their medications. In particular, patients with AIDS and known gastrointestinal diseases have problems absorbing these drugs. In addition, because MDR-TB and MAC are so difficult to treat, TDM with the antimycobacterial drugs offers the clinician a chance to ensure that the patient achieves serum concentrations above the MIC of the pathogen. TDM has become the standard of practice at the National Jewish Center for Immunology and Respiratory Medicine. By combining specific and sensitive assays, carefully collected samples, and clinical expertise, we are able to control and optimize antimycobacterial drug therapy. We continue to refine our approach with ongoing pharmacokinetic and pharmacodynamic research, including the development of population pharmacokinetic models. We hope that these efforts will provide insight into the nature of current therapeutic problems. We also hope they will help us improve the clinical outcomes of our patients.
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PMID:Using therapeutic drug monitoring to dose the antimycobacterial drugs. 909 12

Mycobacterium avium frequently causes disseminated infection in advanced AIDS. Some quinolones including ciprofloxacin and sparfloxacin have anti-M. avium activity in cell-free systems in vitro. Acidic conditions within macrophages and variable intracellular drug penetration and compartmentalization may, however, alter the susceptibility of M. avium to these antimicrobial agents in human tissues. We, therefore, tested the activities of 47 quinolones against M. avium in a human monocyte infection model using ciprofloxacin susceptible (MIC = 0.25 mg/L) and resistant (MIC = 4 mg/L) patient isolates. Monocytes from healthy subjects were infected with M. avium and cultured with or without antimicrobials for 8 days. Some quinolones had poor activity against M. avium in the monocyte culture system despite low MICs (< or = 0.25 mg/L); in contrast, some quinolones with MICs > 32 mg/L showed some inhibition of M. avium growth within monocytes at 4 mg/L. Six quinolones synthesized based on structure-activity analysis were more active than ciprofloxacin. These data underscore the importance of evaluating drug activity of new antimicrobial agents against intracellular pathogens in a macrophage model as well as in cell-free systems.
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PMID:Comparison of the activity of fluoroquinolones against Mycobacterium avium in cell-free systems and a human monocyte in-vitro infection model. 918 6

To investigate the emergence of rifampin resistance in Rhodococcus equi strains isolated from foals and their environment in Japan, we compared the in vitro antimicrobial susceptibilities to rifampin of 640 isolates from 64 infected foals and 98 soil isolates from their horse-breeding farms. As a control, 39 human isolates from patients with and without AIDS were also tested for susceptibility to rifampin. All of the isolates showed rifampin sensitivity, except isolates from one infected foal and two patients with AIDS that showed rifampin resistance. To investigate the emergence of rifampin-resistant R. equi in the infected foal, which had received rifampin monotherapy for a month before euthanasia, 99 isolates of R. equi from the lesions and 20 isolates from the intestinal contents of the one foal with rifampin-resistant organisms were analyzed for rifampin susceptibilities, pathogenicities, and ribotypes. Of the 99 isolates from the lesions, all of which were virulent R. equi strains containing a virulence plasmid with a size of 85 or 90 kb, 90 (91%) isolates were rifampin resistant (MIC, > or = 12.5 microg/ml). On the other hand, of the 20 isolates from the intestinal contents, 11 (55%) isolates showed rifampin resistance (MIC, > or = 25 microg/ml), and 5 of them were avirulent R. equi strains. Among these 101 rifampin-resistant R. equi isolates with and without virulence plasmids characterized by ribotyping, 58 were type I, 20 were type II, 11 were type III, and 12 were type IV. These results demonstrated that at least eight different rifampin-resistant R. equi strains emerged concurrently and respectively from the different lesions and intestinal contents of the infected foal.
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PMID:Emergence of rifampin-resistant Rhodococcus equi in an infected foal. 919 23

The MIC values of fluconazole were determined for 96 Candida isolates (56 C. albicans, 15 C. glabrata, 9 C. krusei and 10 C. tropicalis). The methods employed for antifungal susceptibility testing were: microdilution according to the protocol M27-P of the NCCLS (M 27-Pmicro) using RPMI 1640 medium or HR medium following Troke & Pye (HRmicro) as well as the agar diffusion method by means of the Etest (YNB agar). The in vitro results were compared with the clinical outcome of patients. All C. albicans isolates received from AIDS patients with fluconazole-refractory candidosis showed MICs of > or = 6.25 mg/ml (M27-Pmicro) or > or = 25 mg/ml (MRmicro) and Etest). On the other hand some MICs of C. albicans isolates from AIDS patients with fluconazole-sensitive candidosis were also beyond these breakpoints. Therefore, a possible success of a fluconazole therapy cannot unequivocally be predicted from the MIC value determined in vitro.
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PMID:[Comparison of three antifungal susceptibility testing methods for the in vitro testing of Candida isolates from patients with HIV infection]. 919 45

We investigated the stereoselective inhibition of growth and ergosterol biosynthesis by SCH39304 in the pathogenic fungus Cryptococcus neoformans obtained from four AIDS patients who failed fluconazole therapy and compared the results to those obtained with a wild-type strain. For all strains, the MICs of the RR isomer were approximately half those of the racemate, with the SS enantiomer showing no inhibitory activity. The 50% inhibitory concentrations for in vitro ergosterol biosynthesis correlated with the MIC data, indicating stereoselective inhibition of their target P-450 enzyme, sterol 14alpha-demethylase, as the cause of this difference. The RR enantiomer produced classical type II spectra on addition to microsomal extracts of the strains, whereas the SS enantiomer showed an absence of binding. Stereo- and regio-specific localization of N-1 substituent groups of SCH39304 within the active site of the enzyme determined the unique discrimination between its two enantiomers, and the inability to bind to sterol 14alpha-demethylase is also true of other P-450 enzymes contained in the microsomal fraction. As previously observed for other antifungal azoles, isolates obtained following failure of fluconazole therapy showed resistance to SCH39304 and its RR enantiomer. This resistance could be associated with an alteration in the sensitivity of ergosterol biosynthesis in vitro. These alterations did not cause any changes allowing the SS enantiomer to bind to the P-450 mediating sterol 14alpha-demethylation.
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PMID:Stereoselective interaction of the azole antifungal agent SCH39304 with the cytochrome P-450 monooxygenase system isolated from Cryptococcus neoformans. 921 Jun 67

It has been proposed that dapsone in combination with pyrimethamine could be used for prophylaxis of both Pneumocystis carinii pneumonia and encephalitis due to Toxoplasma gondii. Ten patients with AIDS undergoing lumbar puncture for diagnostic purposes were studied in order to assess the penetration of dapsone into CSF. Blood and CSF samples were obtained between 3 and 72 h following administration. Six patients had received oral dapsone for at least 1 month at the dosage regimen of 100 mg twice of three times weekly and four patients had received a single oral 100 mg dose. Dapsone concentration in CSF ranged from 0.013 to 0.296 mg/L while concentrations in plasma ranged from 0.018 to 1.231 mg/L. The CSF:plasma concentration ratio ranged from 0.21 to 2.01. The MIC of dapsone in combination with pyrimethamine against T. gondii is unknown, and further data are required to confirm whether the CSF concentrations of dapsone found in our study are sufficient to inhibit T. gondii growth in patients infected with human immunodeficiency virus (HIV). The high interpatient variability of dapsone CSF concentrations warrants further studies in selected categories of patients with HIV infection.
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PMID:Penetration of dapsone into cerebrospinal fluid of patients with AIDS. 924 13

In addition to the activity against a number of retroviruses, azidothymidine (AZT) has antibacterial activity against many bacteria. The effect of AZT on 224 bacterial species, including 25 strains of Salmonella spp. isolated from HIV-positive patients, was tested. AZT had no activity against all the strains of tested Gram-positive bacteria and Pseudomonas species (MIC > 128 micrograms/ml), whereas a different activity against Enterobacteriaceae (MIC range, 128 to 0.06 micrograms/ml) was found. In particular 76% of Salmonella spp. isolated from HIV-positive patients showed MICs > 1 microgram/ml, whereas similar MICs value were found in 50% of the Salmonella strains isolated from HIV-negative subjects. In addition, strains of Salmonella isolated from stools were more resistant to AZT when compared to strains isolated from blood even if this difference was not statistically significant. No correlation was found between length of therapy and Salmonella resistance to AZT in HIV-positive patients and a low incidence of Salmonella relapses in subjects treated with AZT was observed. The possibility that AZT may have an ancillary benefit in controlling some bacterial infections in AIDS patients is discussed.
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PMID:In vitro antimicrobial properties of azidothymidine (AZT). 933 Jun 65

Macrolide resistance is an emerging problem in AIDS patients who receive these agents for treatment or prophylaxis against Mycobacterium avium (MAC) infection. We compared the emergence of resistant MAC strains during therapy with clarithromycin (clarithromycin resistance was defined as MIC > or = 32 microg/ml) and azithromycin (azithromycin resistance was defined as MIC > or = 128 microg/ml) in C57BL/6 beige mice. Treatment with clarithromycin and azithromycin resulted in a decrease of 98.5% in the number of viable bacteria in spleens at week 8 and 99% at week 12 compared with the number of bacteria present in spleen before the initiation of therapy (P < 0.001). Splenic homogenates were also plated onto 7H11 agar plus clarithromycin at 32 microg/ml or azithromycin at 128 microg/ml. Resistance emerged significantly more often in mice treated with clarithromycin (100% of treated mice at both 8 and 12 weeks) than in those receiving azithromycin (0% at week 8 and 14% at week 12). The frequencies of resistance of the MAC population in the spleen to clarithromycin were 2.1 x 10(-3) at week 8 and 1.1 x 10(-2) at week 12, whereas resistance to azithromycin was absent at week 8 (all mice) and was approximately 3.5 x 10(-5) (mean for the three positive animals) at week 12. Clarithromycin was more effective in initial reduction of MAC burden in tissue after 8 and 12 weeks of treatment, but resistant strains emerged significantly more frequently after treatment with clarithromycin than after treatment with azithromycin.
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PMID:Emergence of Mycobacterium avium populations resistant to macrolides during experimental chemotherapy. 944 83

Cryptococcus neoformans strains isolated from 207 HIV positive and HIV negative patients hospitalized in Northern Italy were serotyped by slide agglutination. One Brazilian HIV negative woman was infected by var. gattii serotype B and all the other patients by var. neoformans, serotype D in 71%, serotype A in 24.6% and serotype AD in 3.4%. No difference was observed between subjects with serotypes A and D in HIV coinfection, exposure categories for AIDS, age, sex, and CD4 count of HIV positive patients. Meningeal and respiratory tract involvements and prostatic reservoir occurred with comparable frequency in AIDS patients infected by serotypes A and D. Skin lesions were observed only in serotype D infections, occurring in 12.6% of HIV positive and 58.3% of HIV negative patients infected by this serotype. Serotype A was found less susceptible to fluconazole than serotype D: 53.7% of serotype A strains had a MIC > or = 25 micrograms ml-1 compared to 17.7% of the serotype D isolates. On the other hand, both serotypes were highly susceptible to itraconazole.
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PMID:Prevalence of serotype D in Cryptococcus neoformans isolates from HIV positive and HIV negative patients in Italy. 947 13

A chequerboard titration broth microdilution method, performed according to the recommendations of the National Committee for Clinical Laboratory Standards, was applied to study the in-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against 30 strains of Candida albicans isolated from the oral cavities of AIDS patients. MICs were determined spectrophotometrically at 490 nm and read at either 24 h or 48 h. The end-point was defined as the drug concentration resulting in > or = 90% inhibition of growth relative to control growth. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 93% (28 of 30) of terbinafine-amphotericin B interactions, in 47% (14 of 30) of terbinafine-fluconazole interactions and in 43% (13 of 30) of terbinafine-itraconazole interactions; antagonism (FIC > 2.0) was not observed. Where synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when used in combination. Reading the MICs on day 2 did not significantly affect the mode of interaction of terbinafine-triazoles, while for terbinafine-amphotericin B the proportion of synergic interactions dropped from 93% (28 of 30) to 30% (nine of 30; P = 0.0001). Antagonism was not observed for any drug combination even at 48 h. Minimum fungicidal concentrations (MFCs) of all drugs alone and in combination were determined against five isolates. Neither terbinafine nor the two triazoles showed fungicidal activity when tested alone or in combination. The fungicidal activity of amphotericin B was slightly enhanced when combined with terbinafine, there being a decrease of two-fold dilutions in the amphotericin B MFCs against all five isolates tested. Thus terbinafine enhances the activities of amphotericin B and triazoles against C. albicans in vitro. Clearly, clinical studies are warranted to elucidate further the potential utility of these combination therapies.
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PMID:In-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against clinical isolates of Candida albicans. 951 Oct 38


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