Near-drowning complicated by brain abscess due to Petriellidium boydii.

Extracutaneous infection from Petriellidium boydii is an unusual occurrence despite the ubiquity of the organism in nature. Central nervous system infection by this organism is extremely rare, only seven previous reports having been found. The rarity of this manifestation prompted the report of a brain abscess occurring in a previously healthy youth after a near-drowning. The source of the infection was likely to have been the river water at the accident site, from which P boydii was isolated. Although previous in vitro susceptibility data and failure of amphotericin B therapy in a similar infection suggested miconazole treatment might be beneficial, the organism causing the brain abscess was resistant to miconazole and amphotericin B. This report emphasizes the urgent need for safer and more predictably effective alternatives to currently available antifungal agents.

Iontophoresis of gentamicin into aphakic rabbit eyes. Sustained vitreal levels.

The authors evaluated the intraocular penetration of gentamicin (50 mg/ml) into aphakic rabbit eyes following anodal iontophoresis (0.75 mA for 10 min). Gentamicin levels were determined at 0.5, 4, 8, 16, and 24 hrs after iontophoresis (n = 6 eyes for each time) using an agar diffusion bioassay. Peak levels of 72.04 +/- 6.1 (means +/- SE) micrograms/ml for the corneas and 77.8 +/- 3.0 micrograms/ml for the aqueous humor were obtained at 30 min after iontophoresis. The peak vitreous level was 10.4 +/- 0.4 micrograms/ml, which was found at 16 hrs after iontophoresis. Therapeutic levels of 6.2 +/- 3.0 micrograms/ml were still present in the vitreous humor 24 hrs after iontophoresis. Iontophoresis appears to be an effective noninvasive method for delivering therapeutic levels of gentamicin into ocular tissues and fluids of the aphakic rabbit eye.

The promotional effect of bone wax on experimental Staphylococcus aureus osteomyelitis.

The consequences of using surgical bone wax are not well studied. We evaluated the infection-promoting potential of sterile bone wax in a rat model of chronic Staphylococcus aureus osteomyelitis. The addition of bone wax greatly reduced the quantitative bacterial inoculum (log colony-forming units) required to establish chronic osteomyelitis in 50% and 100% of challenged animals. The 50% infection rate was reduced from log 6.9 to 2.6 and the 100% infection rate from 8.2 to 4.4, respectively (p less than 0.015, t test for parallelism). Separate experiments were done 10 to 30 minutes after inoculation with only log 6.4 staphylococci. Tibiae of animals that received bone wax yielded more organisms than those that did not (log 2.76 +/- 0.68 versus 1.72 +/- 0.94, p less than 0.01). At 24 hours quantitative colony counts were not significantly different whether animals received wax or not (log 5.02 +/- 0.42 versus 4.43 +/- 0.65, p greater than 0.09). These studies suggest that the routine surgical use of bone wax should be reassessed.

Ocular pharmacokinetics of ceftriaxone following subconjunctival injection in rabbits.

Aqueous and vitreous kinetics were studied after anterior subconjunctival injection of 100 mg of ceftriaxone sodium in phakic and aphakic rabbit eyes. Mean peak ceftriaxone concentrations (microgram per milliliter +/- SE, n = 3 to 5 rabbits per determination) were as follows: phakic eyes, 159.5 +/- 42 at one hour in aqueous humor and 25.3 +/- 6.6 at two hours in vitreous fluid; aphakic eyes, 105.1 +/- 20.5 at one hour in aqueous humor and 43.1 +/- 15.4 at one hour in vitreous humor. The ability of ceftriaxone to eliminate an incipient bacterial infection was also evaluated. Ten aphakic rabbits were challenged intravitreally with 700 colony-forming units of Staphylococcus aureus. Six of the ten immediately received subconjunctival injections of ceftriaxone sodium (100 mg). At 48 hours following the challenge, all four control eyes yielded greater than 5.6 X 10(5) colonies per milliliter. In the six eyes receiving ceftriaxone, five were sterile and one yielded 1.4 X 10(2) colonies per milliliter.

Pharmacokinetic analysis of intravitreal ceftriaxone in monkeys.

Ocular toxic effects of intravitreally injected ceftriaxone sodium and its rate of clearance after a single dose were studied in rhesus and cynomolgus monkeys. Doses of 2, 2.5, and 3 mg/0.1 mL were injected into the vitreous cavity. Electroretinograms performed 15 minutes, 24 hours, one week, and two weeks after injection were not significantly different from preinjection electroretinograms. Lens opacification occurred in one eye receiving 2.5 mg of ceftriaxone. Histopathologic findings in the retina were normal in all eyes injected intravitreally. Levels of ceftriaxone after a 2-mg intravitreal dose were 609 mg/L at 0 hours, 434 mg/L at 24 hours, and 19 mg/L at 100 hours in the vitreous; and 1 mg/L at 0 hours, 116 mg/L at 24 hours, and 9 mg/L at 100 hours in the aqueous.

Intravitreal ceftriaxone in a rabbit model. Dose- and time-dependent toxic effects and pharmacokinetic analysis.

Ceftriaxone's toxic effects were assessed in albino rabbits after intravitreal injection. Doses up to 5 mg did not alter the B-wave amplitude. Following 7.5-and 20-mg doses, B-wave amplitude ratios were depressed at 24 hours and normal at seven and 14 days. A 50-mg dose caused a temporarily flat B-wave 24 hours after injection. At two weeks this ratio exhibited a moderate increase but remained 2 SDs below the mean preinjection ratio. Eyes receiving up to 20 mg were normal histologically at 14 days. A 50-mg dose induced generalized retinal edema and disruption of the retinal layers 24 hours after injection; at two weeks there were no histologic changes in the retina. Immediately after a 2-mg intravitreal injection, vitreous ceftriaxone levels were 1,345 +/- 4.9 mg/L; by 72 hours they had decreased to 17.6 +/- 1.4 mg/L. The mean peak aqueous level was 80.2 +/- 12.2 mg/L at 72 hours.

Tuberculosis surveillance: lessons from a cluster of skin test conversions.

Mycobacterium tuberculosis has reemerged as a significant public health problem. Elderly persons, especially those in long-term care facilities, are among those at high risk for infection with M. tuberculosis. Frequently, their symptoms are not clearly indicative of M. tuberculosis, and the diagnosis may thus be missed. We discuss the investigation of a cluster of skin test conversions on one locked unit in our long-term care facility. During the epidemiologic investigation, four of 25 patients who had previously had negative results of purified protein derivative testing (16%) and eight of 95 employees (11%) had skin test conversions. Despite a comprehensive, costly evaluation, the index case was not found. We identified weaknesses in our employee and patient M. tuberculosis surveillance programs. Employee baseline purified protein derivative testing data were inadequate. Annual skin tests for employees with previously negative results were not mandatory. There was no mechanism in place to encourage compliance. We developed a plan to educate personnel about the reemergence of M. tuberculosis, signs and symptoms in elderly patients, and the placement and interpretation of purified protein derivative skin tests. Documentation of purified protein derivative surveillance of both patients and employees was computerized. The number of inpatient and outpatient negative-pressure rooms was increased. Appropriate personal protective equipment was made available for use in high-risk situations.

Animal models of osteomyelitis. Knowledge, hypothesis, and speculation.

Each animal model has provided insights. Particularly important was the considerable resistance of bone to infection without manipulation (no morrhuate, fracture, rod, wax, or prosthesis). Such perturbations allow bone infection with much smaller inocula. Typical inocula decreases are 1000 to 10,000 fold. Staphylococci may have a selective advantage in bone because of specialized or tropic binding, perhaps to cartilage or collagen. Osteoclast-induced resorption of hydroxyapatite might explain the distribution of some osteomyelitis. Increased osteoclast activity could link the susceptible metaphyseal regions, the repetitively traumatized diabetic foot, a history of blunt bone trauma, fracture, and perhaps even nearby soft tissue infection. Diagnosis remains difficult; gallium-67 and indium111 labeled WBC probably deserve additional investigation. Therapeutic failures in the rabbit and rat models mirror clinical experience. Clindamycin, rifampin, and quinolones are promising. Neither systemic nor local antimicrobial prophylaxis is well studied yet.

Prophylactic antibiotics in colon surgery.

One hundred twenty-three patients undergoing elective colon surgery were prospectively and randomly assigned to receive either three 1-g perioperative doses of intramuscular cephaloridine or three 1-g preoperative doses of both oral erythromycin base and neomycin sulfate. All patients had their bowels thoroughly cleansed mechanically. The groups were comparable in age and nutritional status. Eight wound infections occurred in the 65 patients receiving cephaloridine (12.3%) v one in the 58 receiving erythromycin and neomycin (1.7%). The difference was statistically significant. Eight of nine infected patients had only wound infections; the majority of cultures yielded Bacteroides fragilis. Serum and tissue antimicrobial concentrations were determined in the first 70 randomized patients at operation. Mean (+/- SD) cephaloridine levels were 14.7 +/- 10.2 and 10.5 +/- 10.0 mg/L in serum and tissue, respectively, compared with 1.98 +/- 1.58 and 0.699 +/- 1.146 mg/L for serum and tissue erythromycin levels.

Multistrain comparison of three antimicrobial prophylaxis regimens in experimental postoperative Pseudomonas endophthalmitis.

We compared subconjunctivally administered ceftazidime and BMY 28142, two third-generation cephalosporins, to a regimen of gentamicin and cefazolin for their ability to prevent experimental Pseudomonas postoperative endophthalmitis in rabbits. After extracapsular lens extraction, an inoculum of Pseudomonas was injected into the vitreous; one of the three antimicrobial regimens was then administered subconjunctivally. All 25 eyes treated with gentamicin and cefazolin become infected (P = 1). Two of 25 eyes treated with BMY 28142 became infected (P less than .001). None of the 25 eyes treated with ceftazidime became infected (P less than .001).

Infections or neoplasm as causes of prolonged fever in cancer patients.

Thirty-six consecutive patients with cancer who met the classical criteria for fever of unexplained origin (FUO) were identified. A total of 18 patients had infections including all 12 with leukemia, four of 12 with Hodgkin's disease, and two with solid tumors. Fungal infections were found in nine: histoplasmosis, three; candidiasis, three; and aspergillosis, systemic sporotrichosis, or cryptococcal meningitis, one each. Six patients had unresolved pyogenic infections and one had tuberculous pericarditis. Two others had viral etiologies. Granulocytopenia was significantly more common in the FUO patients with documented infections. Clinical or laboratory abnormalities suggesting involvement of a specific organ or organ system provided important clues indicating infections. Morphological examination of biopsy specimens, with cultures, was the best method for diagnosis. In 18 patients, 12 with lymphomas and 6 with solid tumors, only the neoplasm appeared responsible for the fever. In these patients there was a paucity of abnormalities indicating organ system involvement with infection. Regardless, physicians' diagnostic efforts should not be deterred in such patients. Repeated thorough evaluations for infection are warranted.

A serologic response in human infection with Enterobacteriaceae.

Sera from patients infected with Escherichia coli, Proteus, Klebsiella, and Serratia were studied for precipitins to ultrasonic extracts of these organisms in gel-diffusion plates. Sera from 66 per cent of these patients contained precipitins when initially tested. Twenty-four per cent of sera tested in the first week after onset of infection contained precipitins, but this rose to 78 per cent by the third week. Cross-reactions of sera with Pseudomonas antigens were unusual, but were common with other enterobacterial antigen extracts. However, higher titers were usually present to homologous as compared to heterologus antigens. Sera from seven patients contained precipitins to a common enterobacterial antigen. Precipitins to E. coli, Proteus, Klebsiella, and Serratia were detected in only a small proportion of control sera.

Disseminated candidiasis: a comparison of two immunologic techniques in the diagnosis.

Eighty-five subjects were tested for the presence of circulating candidal antigen (CAg) and anti-candidal antibody (CAb) using both an enzyme immunoassay (ELISA) and counterimmunoelectrophoresis (CIE). The 72 studied controls included laboratory volunteers; hospitalized patients without evidence of infection; febrile hospitalized patients without evidence of candidiasis; and patients with superficial candidiasis and candiduria. The control subjects were compared with 13 patients with proven disseminated candidal infection (disease prevalence = 15%). The ELISA CAb test was of greater individual sensitivity (92%) in separating patients with systemic candidiasis from all controls combined than the ELISA CAg, CIE CAg, or CIE CAb test (61%, 15%, 69%, respectively). The CIE CAg test, though specific (100%), was insensitive. Sensitivity, specificity, and predictive values were generally enhanced by employing combinations of tests. Sera from patients with disseminated candidiasis were much more likely to yield a positive result by two or more serologic tests than were control sera (p = less than 0.0004). The sensitivity of combinations ranged from 15% to 92%. The specificity of combinations ranged from 21% to 100%. The predictive value positive of combinations test ranged from 40% to 100%. Predictive value negative of combinations ranged from 69% to 98%. Patients with a variety of superficial and deep candidal infections apparently have detectable circulating CAb and/or CAg. The ELISA CAb test was superior to the other tests in identifying patients with disseminated candidiasis. Combinations of serologic tests may be superior to individual tests in the diagnosis or exclusion of serious disease due to Candida albicans.

Management considerations for an HIV positive dental student.

Health care workers who are HIV positive or who have AIDS are faced with unique and perplexing problems. Likewise dental students who are HIV positive present a special circumstance that demands review of ethical, legal, managerial, and medical considerations. The purpose of this paper is to describe the management considerations at the Medical College of Georgia following a recent report of an HIV positive dental student. The administration assembled a diverse team of experts for advice in the situation. This group assumed that the circumstance was a potential crisis with possible serious long-term implications. Therefore detailed planning, appropriate announcements, and careful management have been the administration's principle goal for several weeks. The key management strategies and actions are described from the time of notification of the student's HIV antibody test results through the initial testing of the patient population subgroup.

Antimicrobial therapy for chronic osteomyelitis in adults: role of the quinolones.

The development of antimicrobial therapy for osteomyelitis is reviewed. The disease, especially when chronic, is notoriously resistant to antibiotic therapy. The duration of disease defining chronicity has decreased considerably in the last 30 years. Successful therapy reflects increased appreciation of the combined roles of surgical debridement and prolonged antimicrobial courses. Parenteral high-dose beta-lactam agents yield clinical success for many patients with chronic osteomyelitis, particularly with prolonged administration and surgical debridement. Over the last decade, the initial success of oral quinolone therapy for gram-negative osteomyelitis was exploited further for staphylococcal diseases. Open clinical trials and comparative trials suggest success rates approximating those achieved with parenteral beta-lactams, particularly with appropriate surgery and adequate duration of therapy. The early results with quinolones and rifampin for prosthesis-related infection are encouraging. Overall, oral quinolones provide a new and frequently proportionate response to a disease that is difficult to treat.