Bernhard Ruf

Effectiveness of the macrolide clarithromycin in the treatment ofMycobacterium avium complex infection in HIV-infected patients

SummaryIn a randomized double-blind study, nine mycobacteremic patients with AIDS-related disseminatedMycobacterium avium complex (MAC) infection received clarithromycin or placebo in addition to a basic regimen that included isoniazid, ethambutol and clofazimine. All four patients receiving clarithromycin showed blood culture conversion and clinical response. Of the five patients treated without clarithromycin, two showed resolution of mycobacteremia and clinical reponse, while another two died without having shown response. The remaining patient deteriorated until a switch from placebo to clarithromycin led to blood culture conversion and rapid clinical improvement. After finishing six weeks of intensive treatment, clarithromycin was given in an open maintenance phase to all patients, initially in combination with rifabutin for 24 weeks and then alone. One patient had a relapse of MAC infection while receiving clarithromycin alone. The relapse was associated with acquired resistance to the drug. Clarithromycin appears to be a promising component of multi-drug therapy for patients with MAC infection. Monotherapy can lead to drug resistance.ZusammenfassungNeun AIDS-Patienten mit disseminierterMycobacterium avium complex (MAC)-Infektion wurden in einer randomisierten Doppelblind-Studie mit Clarithromycin oder Plazebo behandelt, die zu einer Basiskombination aus Isoniazid, Ethambutol und Clofazimine hinzugegeben wurden. Alle vier mit Clarithromycin behandelten Patienten sprachen auf die Therapie an. Von fünf ohne Clarithromycin behandelten Patienten sprachen zwei auf die Therapie an, während zwei andere ohne Therapieeffekt verstarben. Ein Patient verschlechterte sich kontinuierlich, bis der Austausch von Plazebo gegen Clarithromycin zur Blutkultur-Konversion und Rückbildung von Krankheitserscheinungen führte. Nach einer sechswöchigen Akuttherapie-Phase erhielten alle Patienten Clarithromycin in einer offenen Studie zur Rezidiv-Prophylaxe, zunächst in Kombination mit Rifabutin für 24 Wochen und anschließend als Monotherapie. Ein Patient hatte ein Rezidiv der MAC-Infektion, das in der Monotherapie-Phase auftrat und mit einer erworbenen Resistenz gegen das Medikament assoziiert war. Clarithromycin ist eine vielversprechende Substanz für ein Kombinationsregime zur Behandlung der MAC-Infektion. Eine Monotherapie kann zur Resistenz-Entwicklung führen.

The incidence of legionella pneumonia: A 1-year prospective study in a large community hospital

In a 1-year prospective study, 28 of 476 pneumonia patients (5.9%) were diagnosed as having legionella pneumonia. Legionella pneumonia was diagnosed in 12 (5%) of 240 community-acquired pneumonias and in 16 (6.8%) of 236 nosocomial pneumonias. Four methods of establishing diagnosis were used: serum antibody detection, direct proof of legionellae by immunofluorescence, culture, and legionella antigen detection in urine. The latter method proved to be clearly advantageous to all other methods in establishing the diagnosis. Twelve of the 28 patients (42.8%) died; all of them had severe underlying diseases. The fatality rate in patients treated with erythromycin was 18.8% (3/16 cases) and 75% (9/12 cases) in patients treated with antibiotics other than erythromycin. In 57.1% (16/28 patients) legionella pneumonia was acquired nosocomially. The results of our study underscore the need to use a broad spectrum of legionella diagnostic methods routinely and to administer antibiotics effective against legionellae in cases of pneumonia of unknown cause.

High-performance liquid chromatography determination of pyrimethamine, dapsone, monoacetyldapsone, sulfadoxine, and N-acetyl-sulfadoxine after rapid solid-phase extraction.

A solid-phase extraction procedure and a corresponding high-performance liquid chromatographic technique based on methods previously published by Edstein et al. (Edstein M. Quantification of antimalarial drugs. I. Simultaneous measurement of sulphadoxine, N4acetylsulphadoxine and pyrimethamine in human plasma. J Chromatogr 1984;305:502-7; Edstein M. Quantification of antimalarial drugs. II. Simultaneous measurement of dapsone, monoacetyldapsone and pyrimethamine in human plasma. J Chromatogr 1984;307:426-31) were developed for simultaneous determination of either dapsone (DDS), monoacetyldapsone (MADDS), and pyrimethamine (PYR) or sulfadoxine (SDX), N-acetyl-sulfadoxine (NAS) and pyrimethamine in plasma. Solid-phase extraction was achieved using C-18 extraction columns. An ionpair chromatography was performed on a C-18 analytical column (mu Bondapak C-18, 300 x 3.9 mm I.D.). Gradient elution with methanol, acetonitrile, PIC B6 reagent (1-hexanesulphonic acid), and water as mobile phase was applied. Ultraviolet detection was done at 210 nm for PYR, at 254 nm for SDX and NAS, and at 295 nm for DDS and MADDS. The extraction recoveries averaged 92.1% for PYR, 87.6% for DDS, 87.5% for MADDS, 91.2% for SDX, and 92.4% for NAS. The limit of quantification using 1.0-ml plasma samples was 15 ng/ml for PYR, DDS, MADDS, NAS, and 25 ng/ml for SDX (precision < 15%).

Staphylococcus colonization, mortality and morbidity in hemodialysis patients: 10 years of observation

Colonization with Staphylococci is widely distributed among patients with end-stage renal disease who are receiving hemodialysis (HD). In addition to more intensive care and use of artificial devices, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection has increased. Such colonization has recently been associated with a more than doubled mortality rate in HD patients. However, it is not clear whether the (presumably increasing) incidence of methicillin-sensitive Staphylococcus aureus (MSSA) colonization is associated with MRSA and/or morbidity and mortality. We therefore established a screening program in our HD population (n=156) and followed these patients over 10 years. We discovered eighty-eight MSSA-colonized patients and one MRSA-colonized patient by cross-sectional and admission-related screenings between 2000 and 2010. The morbidity and mortality of the HD patients was not related to MSSA colonization. The MSSA colonization rate decreased slightly during the 10-year observation period. We conclude that the incidence of MRSA colonization in our unit was lower compared to that reported in the literature. The reasons for this finding are complex and require further investigation. The incidence of MSSA colonization was frequent but did not impact morbidity or mortality.