Cutaneous tuberculosis of the penis in an HIV-infected adult.

We report a case of cutaneous penile tuberculosis (TB) in an HIV-positive man masquerading as a sexually transmitted infection. This case details a patient who was diagnosed with HIV and achieved virological suppression on antiretroviral therapy. He subsequently stopped his therapy and travelled to a TB-endemic area. Upon return, new penile lesions developed and cultures were positive for Mycobacterium tuberculosis. This diagnosis was accomplished due to an inguinal immune reconstitution inflammatory response after the patient restarted antiretroviral therapy. This case demonstrates the rarity of penile TB and cutaneous TB in association with HIV.

Treatment of coccidioidal meningitis with fluconazole.

Fluconazole was administered at doses of 50-400 mg/d to 18 patients (15 men, three women) with coccidioidal meningitis. After a mean duration of treatment of 9.8 months, 10 (67%) of 15 assessable patients had responded, one (7%) of 15 had partially responded, and four (27%) of 15 had not responded to therapy. Five (63%) of eight assessable patients receiving fluconazole as sole therapy responded or partially responded. Two patients discontinued fluconazole after initially responding to therapy, and both experienced relapse. The toxicity of fluconazole remains minimal at doses to 400 mg/d. The penetration of fluconazole into cerebrospinal fluid is substantial at all doses studied. Thus fluconazole continues to show promise even as sole therapy against coccidioidal meningitis. Not all patients respond, however, and relapse may be a problem with the currently studied doses and durations of therapy.

Coccidioidal spondylitis.

A review of twelve cases in which disseminated coccidioidomycosis caused localized infection of the spine showed that eight of the twelve patients were alive and well with no evidence of active infection an average of eleven years after onset (range, two to thirty-five years). One patient who was followed for more than twenty-three years had a slowly developing neurological impairment in the lower extremities as a result of lumbosarcral destruction instability. One patient died early in the course of the disease from fulminating cervical spondylitis and quadriplegia. A second patient had a paraplegia from thoracic spondylitis. On patient had no evidence of active spondylitis five years after the onset of the disease, but then died of coccidioidal meningitis. All patients were treated with intravenous amphotericin at some time in the course of their illness, although its effect was not always dramatic. The three patients with neurological impairment did not undergo spine fusion, but most of the others had that operation. Surgical evacuation of abscesses and debridement of infected bone was also performed in many cases.

Clinical pharmacology of amikacin and kanamycin.

During and after a 4-hr intravenous infusion of amikacin and kanamycin in a cross-over study in healthy adult male volunteers, average concentrations of drug in serum were similar, with half-lives of approximately 2 hr. Apparent volumes of distribution at the steady state averaged 30% of body weight, and the rate of renal clearance was less than the rate of creatinine clearance (83 vs. 120 ml/min), a finding that indicates tubular reabsorption. The rate of serum clearance was greater than the rate of renal clearance (100 vs 83 ml/min). Urinary excretion in 24 hr averaged 94% of the dose, and there was no binding of serum proteins. In another cross-over study, volunteers received single intramuscular injections of these antibiotics. Peak concentrations of drug in serum after 45 min to 2 hr averaged 19.9 and 19.0 mug/ml for amikacin and kanamycin, respectively. Serum half-lives between 4 and 8 hr after administration of drug were 2 hr, and an average of 94% of the dose was recovered in the urine in 24 hr. Thus, the pharmacologic properties of amikacin and kanamycin were virtually identical.

Ticarcillin vs carbenicillin: clinical pharmacokinetics.

The pharmacokinetic characteristics of ticarcillin, a semisynthetic penicillin more active than carbenicillin against Pseudomonas, were compared to those of carbenicillin in 12 healthy volunteers. Following an intravenous infusion of 2 gm in 5 min, there was a lower average serum level for ticarcillin (218 mug/ml) than for carbenicillin (301 mug/ml), but after 2 hr the differences were not significant. The biologic half-life of ticarcillin was slightly longer than that of carbenicillin (72 and 65 min, P smaller than 0.01) and its volume of distribution was larger (15.7 and 12.3 l, P smaller than 0.01). Eighty-six per cent of the dose of ticarcillin and 99 percent of the dose of carbenicillin was recovered in the urine in 24 hr. Similar but much less marked blood level differences were noted with 2 gm, 30-min infusions. An intravenous infusion of 1 gm/hr gave average steady-state blood levels of about 124 mug/ml for both antibiotics. Probenecid, administered 1 hr before the infusion, caused significant and similar increases in blood levels, half-lives, and volumes of distribution of the 2 antibiotics. Protein binding in 100 percent human serum was 50 percent and 65 percent for carbenicillin and ticarcillin, respectively. These relatively small but definite differences in the pharmacokinetics of ticarcillin and carbenicillin are not likely to be of clinical significance.

Inactivation of cefazolin, cephaloridine, and cephalothin by methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus.

Cefazolin was more susceptible than cephaloridine and cephalothin to in vitro inactivation by coagulase-positive, penicillinase-producing strains of Staphylococcus aureus. Inactivation (which was greater with methicillin-resistant than with methicillin-sensitive strains) was demonstrated by assay of the antibiotics in broth cultures with simultaneous colony counts and by exposure of the antibiotics to penicillinase powders extracted from S. aureus. Cefazolin was destroyed to a greater extent than was cephaloridine, whereas cephalothin underwent little, if any, destruction. The clinical implications of this degradation, thought by some to be of importance for cephaloridine, might also apply to cefazolin.

Human pharmacokinetics of BL-P1654 compared with ampicillin.

BL-P1654 is a new ureido-penicillin which has significant activity against both pseudomonas and klebsiella. Its pharmacokinetics were evaluated in five studies in four healthy adult male volunteers after 1-g doses given as: 5- and 30-min intravenous infusions, a 30-min infusion 1 h after the oral administration of 1 g of probenecid, and an intramuscular injection. For comparison, volunteers also received a 30-min infusion of 1 g of ampicillin. Serum levels of the antibiotic were found to fit a two-compartment open model using a Burroughs-5500 computer. After a 30-min infusion, peak serum levels of BL-P1654 (72.8 mug/ml [standard deviation] +/- 5.9) were 50% greater than those of ampicillin (53.6 +/- 8.9). Six hours later, the relative difference was even greater (4.58 +/- 0.25 versus 0.35 +/- 0.09). At 75 min after the 1-g intramuscular injection of BL-P1654, peak serum levels averaged 28.4 +/- 10.3 mug/ml. The half-life of BL-P1654 (2.04 h) was significantly longer than for ampicillin (1.15 h), and the renal clearances of BL-P1654 and ampicillin were 79 versus 244 ml/min per 1.73 m(2), respectively. Probenecid produced no significant change in blood levels, volume of distribution, half-life, or renal clearance, indicating that there is no net tubular secretion of this antibiotic.

Pharmacokinetics of metronidazole as determined by bioassay.

The pharmacokinetics of metronidazole, a drug effective in vitro against most anaerobic bacteria and promising in treating anaerobic infections, are described. Serum and urine levels after single and multiple doses in 10 adult male volunteers were measured by an agar well diffusion bioassay using clostridial species as the test organisms under anaerobic conditions. Peak serum levels averaged 11.5 mug/ml and 6.2 mug/ml after single 500-mg and 250-mg doses, respectively. Renal clearance was only 10.2 ml/min per 1.73 m(2), and less than 20% of the administered dose was recovered in the urine as active drug in 24 h. The average serum half-life was 8.7 h, and there was no protein binding as determined by an ultrafiltration method. With multiple doses of metronidazole (500 mg four times a day and 250 mg three times a day), blood levels increased progressively for the first few doses and then leveled off, with no significant accumulation occurring between 3 and 7 days. On 250 mg three times a day, serum levels just before the 8 a.m. dose (12 h after the preceding dose) on the third day averaged 3.9 mug/ml, and before the 8 p.m. dose, 5.7 mug/ml. For the higher, 500-mg dose (four times a day) regimen, the corresponding minimum serum levels were 13.1 mug/ml at 8 a.m. and 21.3 mug/ml at 8 p.m. Peak levels would have been about 10 mug/ml higher, and since the minimum inhibitory concentrations of most anaerobes including Bacteroides fragilis are less than 6 mug/ml, these concentrations should be highly effective therapeutically, even for severe infections.

Synergism of carbenicillin and gentamicin against enterococci.

Carbenicillin and gentamicin were tested for synergism against 25 strains of enterococci by two different methods. Killing curves were determined by doing serial colony counts of broth cultures containing the antibiotics separately and in combination. The combination was synergistic for all 25 strains with 75 and 4 mug of carbenicillin and gentamicin per ml, respectively. Reducing the concentrations to 50 and 3 mug of the antibiotics per ml with four strains significantly reduced the rate of killing of the combination. Synergism was also studied by constructing isobolograms, by using the standard two-dimensional broth dilution checker-board technique, and by measuring the end points both for minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs). Synergism was present for all 25 strains when bactericidal end points (MBCs) were evaluated, but was present for only 7 of the 25 strains when MICs were used to construct isobolograms. The time and effort involved were roughly the same for killing curves and for isobolograms, and it was concluded that neither had a distinct advantage over the other.