Paul D. Hoeprich

Itraconazole treatment of phaeohyphomycosis.

Nineteen patients with phaeohyphomycosis were treated with itraconazole. Of these, 17 were assessable for clinical outcome. Of these, two had received no prior therapy, five had failed amphotericin B therapy, four had failed ketoconazole or miconazole therapy, and five had failed both amphotericin B and azole therapy. One patient had received only prior surgical intervention. Fungi of seven different genera caused disease of the skin in nine patients, soft tissue in nine, sinuses in eight, bone in five, joints in two, and lungs in two. Itraconazole was given in dosages ranging from 50 to 600 mg/day for 1 to 48 months. Clinical improvement or remission occurred in nine patients. Two patients have had stabilization of disease. Six patients failed treatment, one had a relapse after initially successful treatment. Itraconazole appears to be highly effective in some patients with phaeohyphomycosis, including patients refractory to other antifungal agents.

Diagnostic Usefulness and Safety of Transtracheal Aspiration

ACCURATE interpretation of the significance of the isolation of potentially pathogenic microorganisms by culture of expectorated respiratory-tract secretions is frequently impossible. Often, such m...

Treatment of open fractures: a prospective study.

A double-blind prospective study was done to assess the benefit of delaying closure of the wounds associated with open fractures. An additional double-blind study compared the effectiveness of clindamycin versus cefazolin for prophylactic antibiotic coverage. Quantitative cultures of the wounds were accomplished at the time of debridement and again at the time of closure if the wound was not closed initially. Almost half of the wounds were contaminated (46%) at the time of debridement, although the incidence of wound infection was low (6.5%). Gram-negative organisms resistant to the prophylactic antibiotic were recovered initially only eight times, but four of these (50%) became infected. The contaminating organisms in each case were present in high concentration (greater than 10(5) CFU/gm of tissue) at initial culture. The time of wound closure, cefazolin versus clindamycin, and internal fixation of the fracture were not followed by significant differences in the development of clinical infection in this series.

Effect of Nitrogen Dioxide on Pulmonary Bacterial Defense Mechanisms

Effect of nitrogen dioxide on antibacterial activity in vivo was investigated by simultaneously determining physical removal and bactericidal activity rates of murine lung. Mice were exposed to various concentrations of nitrogen dioxide for 17 hours prior to or 4 hours after infection with aerosols of Staphylococcus aureus labeled with radioactive phosphorus (32P). Animals infected and then exposed to levels of nitrogen dioxide above 7.0 ppm showed a progressive decrease in percent pulmonary bactericidal activity which could not be accounted for by physical removal of bacteria. Exposure to levels of nitrogen dioxide of 2.3 ppm or greater for 17 hours prior to staphylococcal infection caused decreases in bactericidal activity. The finding that murine resistance to infection is diminished at exposure levels only slightly above ambient (2.3 ppm) suggests that human populations may incur a similar risk.

Entry of Four Tetracyclines into Saliva and Tears

Although meningococci are susceptible to the tetracyclines by testing in vitro, oxytetracycline (OC) and doxycycline (DC) have failed to eliminate carriage, whereas minocycline (MC) has been effective. Because these congeners differ in lipophilicity, they and tetracycline (TC) were studied in volunteers by assay of serum, saliva, and tears obtained after 5 days of treatment. OC and TC were undetectable or attained concentrations subinhibitory for meningococci in saliva and tears. The concentrations of MC in saliva and tears were equal to or greater than the average minimal inhibitory concentration as long as 12 h post-dose. Near inhibitory concentrations resulted with DC at 100 mg/day; yet, doubling the dose to 100 mg/12 h did not yield concentrations that exceeded the average minimal inhibitory concentration for meningococci. The previous reports of failure or meager entry of DC and MC into saliva probably reflected extraction of these drugs in the paraffin chewed by subjects to stimulate salivary flow. The efficiency of entry of the tetracyclines into the secretions of the noninflamed upper respiratory tract correlates with lipophilicity at physiological pH, enabling prediction of meningococcal chemoprophylactic efficacy.

Successful Treatment of Gram-Negative Bacillary Meningitis with Moxalactam

Meningitis caused by enteric gram-negative bacilli is relatively uncommon but is very difficult to treat despite susceptibility in vitro to many antimicrobics. A major problem appears to be poor entry of many drugs into the central nervous system. Moxalactam is an investigational cephalosporin that attains concentrations in the cerebrospinal fluid that are 15% to 30% of contemporaneous serum concentrations; moreover, it is quite active against many of the enteric gram-negative bacilli. We used moxalactam to treat meningitis caused by Enterobacter cloacae, Klebsiella pneumoniae, and Escherichia coli in four adults and one child, giving up to 100 mg/kg body weight per day by intravenous injection. The concentrations of moxalactam in serum, lumbar, and ventricular cerebrospinal fluid exceeded the minimal lethal concentrations of all causative bacteria. The patients were cured. In this small series, moxalactam, when administered intravenously as the sole agent of therapy, was effective in the treatment of meningitis caused by susceptible gram-negative bacilli.

Nocardial Brain Abscess Cured with Cycloserine and Sulfonamides

Antimicrobic therapy is as important as surgical drainage in the treatment of cerebral nocardial abscess. On the bases of high probability of effectiveness, assured central nervous system penetration, practicality for long-term peroral administration, and the favorable result herein reported, combined antimicrobic therapy using cycloserine and sulfonamides is recommended for cerebral nocardiosis.

Disk Agar Diffusion Susceptibility Testing of Yeasts

A disk agar diffusion method was developed for testing the susceptibility of rapidly growing yeasts in vitro. A totally defined, completely synthetic agar culture medium (synthetic amino acid medium, fungal) and clinical isolates of Candida spp. and Torulopsis glabrata were used. Turbidimetric adjustment of cell suspensions resulted in standard, reproducible inocula, which gave sharp, clear zones of inhibition when applied by an agar overlay method. Optimal disk loads were determined for amphotericin B, amphotericin B methyl ester, 5-fluorocytosine, clotrimazole, and miconazole. Disk potencies were stable over a 2-month period when stored in a vacuum desiccator at −30°C. Using an error ratebounded classification, the zones of inhibition were correlated with both broth dilution and agar dilution minimum inhibitory concentrations (MICs). With amphotericin B and amphotericin B methyl ester, all isolates were susceptible, yielding zone diameters which clustered within 5 mm. Overall correlations between zone diameters and broth dilution MICs with 5-fluorocytosine, miconazole, and clotrimazole were 97, 96, and 82% (excluding T. glabrata), respectively; correlations of zone diameters with agar dilution MICs were 96, 92, and 88%, respectively. Disk diffusion susceptibility testing of yeasts appears to be generally applicable. However, when results are equivocal, quantitative test methods should be used.

Acquisition of Coccidioidomycosis at necropsy by inhalation of coccidioidal endospores

Coccidioidomycosis is accepted as being noncontagious because the infectious arthroconidial form of Coccidioides immitis is not produced in humans and other mammalian hosts. However, disseminated coccidioidomycosis developed in a veterinarian who autopsied a horse with disseminated disease but without draining lesions or productive cough. We postulate transmission occurred by inhalation of tissue-phase endospores aerosolized in the course of dissection.

Comparative Pharmacology of Amphotericin B and Amphotericin B Methyl Ester in the Non-Human Primate, Macaca mulatta

The pharmacokinetics of amphotericin B methyl ester hydrochloride (AME) and commercial deoxycholate-stabilized amphotericin B (AMB) were compared after single doses of 5 mg and 1 mg/kg of body weight, respectively, given intravenously in a period of 3 h to adult female rhesus monkeys (Macaca mulatta). By bioassay, the concentrations of AME were 12.2 to 7.2 times higher in the serum and 7.8 to 2.5 times higher in the urine during the 8 h after infusion. The decline in concentrations of the drugs in sera was consistent with a three-compartment, open pharmacokinetic model; rate constants of transfer of the drugs between the compartments and volumes of distribution were calculated. The overall rate of elimination from the central compartment (the bloodvascular space) was about four times greater for AME than for AMB. Serum urea nitrogen and creatinine concentrations were mildly and transiently increased after infusion of AME, whereas the more severe azotemia that followed infusion of AMB persisted for 5 days. AME was less toxic and achieved a greater urinary outfall than AMB. As the antifungal activity of AME is comparable to that of AMB by testing in vitro, further study is warranted.