Fluoroquinolone antibiotic agents have demonstrated efficacy in the treatment of respiratory tract infections. This analysis was designed to examine the relationship between drug exposure, as measured by the free-drug area under the concentration-time curve at 24 h (AUC 24 )/MIC ratio, and clinical and microbiological responses in patients with community-acquired respiratory tract infections involving Streptococcus pneumoniae. The study population included 58 adult patients (34 males, 24 females) who were enrolled in either of two phase III, randomized, multicenter, double-blind studies of levofloxacin versus gatifloxacin for the treatment of community-acquired pneumonia or acute exacerbation of chronic bronchitis. Clearance equations from previously published population pharmacokinetic models were used in conjunction with dose and adjusted for protein binding to estimate individual patient free-drug AUC 24 s. In vitro susceptibility was determined in a central laboratory by broth microdilution in accordance with NCCLS guidelines. Pharmacodynamic analyses were performed on data from all evaluable patients with documented S. pneumoniae infection using univariate and multivariable logistic regression; pharmacodynamic breakpoints were estimated using Classification and Regression Tree analysis. A statistically significant (P ‫؍‬ 0.013) relationship between microbiological response and the free-drug AUC 24 /MIC ratio was detected. At a free-drug AUC 24 /MIC ratio of <33.7, the probability of a microbiological response was 64%, and at a free-drug AUC 24 /MIC ratio of >33.7, it was 100% (P < 0.01). These findings may provide a minimum target free-drug AUC 24 /MIC ratio for the treatment of infections involving S. pneumoniae with fluoroquinolone antibiotics and provide a paradigm for the selection of fluoroquinolones to be brought forward from drug discovery into clinical development and dose selection for clinical trials. Further, when target free-drug AUC 24 /MIC ratios are used in conjunction with stochastic modeling techniques, these findings may be used to support susceptibility breakpoints for fluoroquinolone antibiotics and S. pneumoniae.The relationship that exists between drug exposure and the MIC for an infectious organism has been shown to be predictive of microbiological eradication (3,4,5,14). Existing data suggest that, for fluoroquinolones, an area under the concentration-time curve at 24 h (AUC 24 )/MIC ratio of 100 to 125 correlates with optimal clinical and microbiological outcomes in seriously ill patients infected with gram-negative enteric pathogens and Pseudomonas aeruginosa (7,8). However, over the past several years there has been considerable controversy as to whether or not this pharmacodynamic target applies to all patient populations and all organisms.Data from in vitro and animal models of infection have recently emerged and suggest that, for Streptococcus pneumoniae, the optimal free-drug AUC 24 /MIC ratio is much lower than 100 to 125. For instance, an in vitro model of pneumococcal infec...

An unusual mycoplasma, which was isolated from the urine of a human immunodeficiency virus-positive male homosexual patient, has an elongated flask shape and two unique sharply divided internal compartments. The tiplike compartment is densely packed with fine granules, and the body compartment is loosely filled with coarse granules consistent with ribosomal structures. The organism has properties of adherence, hemadsorption, and cytadsorption and invades many different types of mammalian cells. Adhesion and penetration apparently involve the terminally located tiplike structure. Cholesterol is required for growth, and the mycoplasma ferments glucose and hydrolyzes arginine, but does not hydrolyze urea. The results of DNA homology studies revealed that this organism is not genetically related to previously described mycoplasma species that have the same biochemical properties. The results of serologic studies demonstrated that this organism is antigenically distinct from all previously described mycoplasmas. We propose that this new mollicute species should be named Mycoplasma penetrans sp. nov. The type strain is strain GTU-54-6A1 (= ATCC 55252).A total of 13 members of the class Mollicutes have been isolated from humans (5, 14, 35). The two most common isolation sites are respiratory and urogenital tracts (5, 3 9 , although isolation from synovial fluids of patients with arthritis (23) and isolation from other anatomical sites have also been reported (15,26,28).The most common mycoplasmas in human urogenital tracts are Mycoplasma hominis and Ureaplasma urealyticum (10, 35). Mycoplasma fernentans, Mycoplasma genitalium, Mycoplasma spermatophilum , Mycoplasma primaturn , Mycoplasma salivarium, and Mycoplasma pneumoniae are less common (5,14,35,37). The frequency of isolation of urogenital mycoplasmas depends in part on the group of individuals studied. Sexual activity, as well as multiple sexual partners, increases the rate of isolation (25). The isolation rates for urogenital mycoplasmas are also different in heterosexual and homosexual males (16).To date, there has been no systematic study of the urogenital mycoplasmas isolated from patients with AIDS. Our previous examination of urine samples from a small number of patients with AIDS in which we used the polymerase chain reaction and cultures for mycoplasmas revealed a high level of M. fermentam infection which was not found in non-AIDS controls (8). In a more comprehensive study, we isolated a previously unknown mycoplasma from urine samples from six patients with AIDS (18). In this paper we describe this organism and its unusual characteristics; we also describe our examination of its distinct biological, serological, and genetic properties, which was carried out in order to establish whether this organism should be given taxonomic status as a new mycoplasma species.* Corresponding author. MATERIALS AND METHODSIsolation and cultivation. SP-4 medium was prepared as described below. A 10-g portion of Tryptone (Difco Laboratories, Detroit, Mich.), 5.3 g of pept...

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Mycoplasma penetrans, a novel mycoplasma isolated from HIV-1-infected patients with AIDS, has pathogenic properties associated with in-vivo virulence. Enzyme-linked immunosorbent assay and western blotting detected a more than 100 times higher frequency of antibodies to the mycoplasma in serum from HIV-1-infected patients with AIDS (40%) than from HIV-negative controls (0.3%). Serum from 20% of HIV-1-infected, symptom-free individuals also had M penetrans specific antibodies. The antibodies' major immunoreactivity was directed against P35 and P38, the two main lipid-associated membrane protein antigens of the organism. Patients attending sexually transmitted disease clinics had a low frequency of antibody (0.9%). None of 178 HIV-negative patients with different non-AIDS diseases, many associated with immune dysfunction and/or low white cell counts, tested positive for the antibodies. M penetrans, apparently not a commensal and not a simple opportunist, is uniquely associated with HIV-1 infection and AIDS.

Thrombocytopenia is a known complication of human immunodeficiency virus Type‐I (HIV‐1) infection, and more data need to be collected on its frequency, severity, and clinical sequelae. We determined the frequency of thrombocytopenia and its relationship to other HIV infection characteristics from a review of records of 1004 HIV‐infected patients attending two outpatient clinics in Washington, D.C. The self‐reported sources of HIV‐1 exposure were male homosexual activity (68j, bisexual activity (10%), heterosexual activity (6%), and intravenous drug use (15%). Fifty‐nine percent of the individuals were white, 37% were black and 94% were male. Fifteen percent had AIDS. Thrombocytopenia occurred more frequently in subjects with AIDS (21.2%) than in HIV‐infected individuals who did not fit clinical criteria for AIDS (9.2%) (p<0.001). Patients with few CD4‐positive cells and an advanced stage of disease were more likely to have low platelet counts: 30% with an absolute CD4 cell count lower than 200/mm3vs 8 % with CD4 counts between 200 and 500 (p<0.00001), and 18.5yo with Stage IV disease compared to 7.6% in Stage I1 (p< 0.001) had platelet counts less than 150000/mm3. Thrombocytopenia was more frequent in white males and older subjects. Although subjects infected by heterosexual exposure had a lower frequency of thrombocytopenia, intravenous drug users and homosexual men exhibited similar frequencies of thrombocytopenia. Of all subjects with platelet counts less than 50000/mm3, 40% reported bleeding and 1 died of an intracranial hemorrhage. Thrombocytopenia occurs frequently in HIV‐infected people, primarily in those with AIDS, low CD4 cell numbers, and advanced stages of diseases