vitamin-k-semiquinone-radical and AIDS-Related-Opportunistic-Infections

To report a case of increased international normalized ratio (INR) in a patient established on warfarin therapy who was then initiated on atovaquone therapy.. A 53-year-old African American male with HIV was prescribed warfarin 5 mg/day for 12 months after diagnosis of idiopathic deep vein thrombosis and bilateral pulmonary emboli (target INR 2.5 [range 2.0-3.0]). The patient required Pneumocystis jiroveci pneumonia prophylaxis and was prescribed atovaquone instead of trimethoprim/sulfamethoxazole therapy because of the latter drug's known interaction with warfarin. The patient's INR rose by greater than 50% (from 2.3 to 3.5) after 7 days of concomitant warfarin and atovaquone. In response, the patient's total weekly warfarin dose was decreased by 5%. Eight days later, the patient's INR was still supratherapeutic at 3.1. Approximately 4 weeks later, his INR was 4.2. One dose of warfarin was withheld and then the total weekly warfarin dosage was decreased by another 10%. Eight days later, the patient discontinued atovaquone therapy but continued on warfarin as prescribed. One day after atovaquone discontinuation, his INR decreased to 1.7. Due to this subtherapeutic INR level, 8 days later the total weekly warfarin dose was increased by 5%. Although a follow-up appointment was scheduled, no further INR values were obtained because the patient's 12-month course of anticoagulation therapy was completed and warfarin was discontinued. The patient did not report any adverse effects or signs or symptoms of hemorrhage while his INR values were supratherapeutic.. Warfarin's potential for interactions with other highly protein-bound drugs, such as atovaquone, can result in displacement from protein binding sites and increased serum concentrations of warfarin. Based on a search of MEDLINE/PubMed, International Pharmaceutical Abstracts, and the Food and Drug Administration MedWatch Adverse Event Reporting Program (all through July 31, 2010), no cases were found of an interaction between atovaquone and warfarin. The Horn Drug Interaction Probability Scale calculated this to be a probable interaction between warfarin and atovaquone.. Although current medication references do not report an interaction between atovaquone and warfarin, knowledge of their pharmacodynamic properties can enable practitioners to anticipate the consequences of a possible transient increase in warfarin serum concentration, such as that seen in our patient, when given concomitantly.

Topics: AIDS-Related Opportunistic Infections; Anticoagulants; Antifungal Agents; Atovaquone; Drug Interactions; Drug Monitoring; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Pulmonary Embolism; Risk Factors; Venous Thrombosis; Vitamin K; Warfarin

Forty strains of nocardioform microorganisms were isolated as clinical specimens including several from AIDS patients in Thailand. Among them, 37 strains were found to belong to the genus Nocardia. Our identification studies revealed that most of the strains (25 strains) belong to the N. asteroides group, i.e., N. asteroides sensu stricto and N. farcinica. Three strains were identified as N. otitidiscaviarum and two strains N. brasiliensis. In addition, 7 strains of rare pathogenic N. transvalensis were also isolated.. Nocardia is an aerobic gram-positive and partly acid-fast bacterium that belongs to the pathogenic actinomycetes. Nocardia can cause both systemic and cutaneous diseases. Cutaneous nocardiosis is thought to be induced by various predisposing factors, the most common of which include corticosteroid therapy, immunosuppressive therapy, and hematological malignancy. In recent years cases of infection have been increasing coupled with the increased use of immunosuppressive agents and the number of AIDS patients. Characterization studies of pathogenic Nocardia isolated clinically in Thailand from 1990 to 1994 were reported. 40 strains of nocardioform microorganisms (Nocardia like actinomycetes with meso-DAP, arabinose, galactose, and mycolic acid) were isolated as clinical specimens including several from AIDS patients. All 40 strains were isolated from clinical specimens at seven hospitals in Bangkok using Sabouraud dextrose agar medium or Ogawa medium. The analysis of mycolic acid profiles on thin-layer chromatography (TLC) plate showed that one strain had the same Rf values as that of Mycobacterium sp. and the remaining 39 strains had similar Rf values to those of Nocardia, Rhodococcus, and Gordona spp. Studies on their menaquinone composition showed that among 39 isolates, 37 strains had MK-8H4 (cycl.) as predominant menaquinone. 2 strains had MK-8(H2) as a predominant menaquinone and both were identified as Rhodococcus spp. 25 strains were found to belong to the N. asteroides group and were further divided into respective species, i.e., 12 strains of N. asteroides in a strict sense and 13 strains of N. farcinica on the basis of Na-citrate utilization, susceptibility to antimicrobial and antitumor agent (tobramycin and 5-fluorouracil), and ability to grow at 45 degrees Celsius. Three strains of N. otitidiscaviarum and two strains of N. brasiliensis were also identified and the remaining seven strains were eventually identified as N. transvalensis. Results of the drug susceptibility pattern test of Nocardia isolates correlated well with those obtained by the traditional identification system. Among 37 cases, there were 10 HIV seropositive and 2 seronegative patients, and the remaining cases were unknown. Further epidemiological studies may be needed to determine a possible association between AIDS and nocardiosis.

Topics: Actinomycetales; AIDS-Related Opportunistic Infections; Bacteriological Techniques; Culture Media; Diaminopimelic Acid; Humans; Mycolic Acids; Nocardia; Nocardia asteroides; Nocardia Infections; Rhodococcus; Thailand; Vitamin K