Pharmacokinetics of intravenously and intramuscularly administered cefepime in infants and children.

The pharmacokinetic characteristics of cefepime were determined after first dose (n = 35) and again under steady-state conditions (n = 31) with a group of 37 infants and children. In eight subjects, a cefepime dose given by intramuscular injection was substituted for an intravenous dose, and disposition characteristics were studied again. Study subjects ranged in age from 2.1 months to 16.4 years, and all had normal renal function. Each patient received 50 mg of cefepime/kg of body weight intravenously every 8 h, up to a total maximum individual dose of 2 g. With the exception of one study patient who received a single cefepime dose for surgical prophylaxis, the patients received cefepime for 2 to 13 days. Elimination half-life (t1/2), steady-state volume of distribution, total body clearance, and renal clearance after first dose administration averaged 1.7 h, 0.35 liter/kg, and 3.1 and 1.9 ml/min/kg, respectively. Although cefepime t1/2 and mean residence time (MRT) were slightly longer for subjects <6 months of age than for older subjects, no differences in cefepime disposition characteristics between first dose and steady-state evaluations were observed. t1/2 (1.8 versus 1.9 h) and MRT (2.3 versus 3.2 h) were slightly prolonged after intramuscular administration, reflecting the influence of absorption from the intramuscular injection site on cefepime elimination. Bioavailability after intramuscular administration averaged 82% (range, 61 to 124%). Fifty-seven percent of the first dose and 88.9% of the last dose were recovered as unchanged drug in urine over the 8- and 24-h sampling periods, respectively. These pharmacokinetic data support a single cefepime dosing strategy for patients > or =2 months of age. The integration of the cefepime pharmacokinetic data generated in our study with the MICs for important pathogens responsible for infections in infants and children supports the administration of a dose of 50 mg of cefepime/kg every 12 h for patients > or =2 months of age to treat infections caused by pathogens for which cefepime MICs are < or =8 mg/liter.

Lung abscess due to Corynebacterium equi. Report of the first case in a patient with acquired immune deficiency syndrome.

A lung abscess and persistent bacteremia due to Corynebacterium equi are described in a bisexual man with the acquired immune deficiency syndrome (AIDS). Eleven of the 12 previously reported cases have occurred in immunocompromised humans. The occurrence of this infection in a patient with AIDS has not been previously described. Development of resistance to beta-lactam antibiotics was noted following initial therapy. Because this organism resembles nonpathogenic organisms, it may easily be overlooked despite its ability to cause serious infection and persist even with aggressive antimicrobial and surgical therapy.

Epidemic typhus in the United States associated with flying squirrels.

Between July 1977 and January 1980, seven cases of sporadic, nonepidemic "epidemic" typhus (Rickettsia prowazekii) were discovered in Virginia, West Virginia, and North Carolina. The reservoir seemed to be the southern flying squirrel (Glaucomys volans), an animal indigenous to the eastern United States; however, the vector or mode of acquisition was not evident. Diagnosis was established principally through complement fixation, indirect immunofluorescence, and toxin neutralization tests. Patients' ages were 11 to 81 years. Most were white women. Six had abrupt onset of illness. Headaches, fever, myalgias, and exanthems were among the presenting complaints. The disease seemed milder than classic louse-born epidemic typhus, but in some instances, it was life-threatening. All patients responded to tetracycline or chloramphenicol. This entity probably is more common than reported, is difficult to recognize, and is produced by an organism seemingly identical to that producing louse-born epidemic typhus.

Nosocomial klebsiella infection in a neonatal unit: identification of risk factors for gastrointestinal colonization.

Sequential outbreaks of infection due to gentamicin-resistant Klebsiella pneumoniae (GRKP) types 30 and 19 occurred in the neonatal intensive care unit (NICU) at the Medical College of Virginia in 1977 and 1978. The extensive epidemiologic investigation carried out included a case-control study, careful review of aseptic technique, and cultures from nursery staff and environment. The gastrointestinal (GI) tracts of the patients were the reservoirs for GRKP, and the epidemic strain was transmitted by hands of personnel. The case-control study showed a significant relationship between acquisition of GRKP by patients and oropharyngeal and GI instrumentation, including use of bag resuscitation, oropharyngeal suctioning, and use of nasogastric feeding tubes. The findings of the case-control study were supported by observation of the patient care techniques practiced by NICU staff. Institution of control measures based on results of the epidemiologic investigation of the first outbreak rapidly brought the second outbreak under control, even though cohorting or use of routine isolation was not possible. Whereas GI colonization and hand transmission have been described previously in outbreaks of K. pneumoniae infections in NICUs, this study is the first to document the mode of inoculation of patients' GI tracts by contaminated hands of personnel.

Sequential outbreaks of infection due to Klebsiella pneumoniae in a neonatal intensive care unit: implication of a conjugative R plasmid.

Sequential outbreaks of infection in a neonatal intensive care unit were due to multiple antibiotic-resistant strains of Klebsiella pneumoniae of different serotypes. In investigations of these outbreaks, the transfer of resistance to gentamicin, ampicillin, cephalothin, carbenicillin, and kanamycin from gentamicin-resistant organisms to standard laboratory recipients and between recipients was observed. Purified plasmid DNA, isolated from all multiple antibiotic-resistant strains, was analyzed by agarose gel electrophoresis, which revealed a common, large plasmid component with a molecular size of 71 megadaltons. Analysis of drug-resistant progeny suggested this plasmid encoded resistance to antibiotics and the information needed for its transmission. The identity of the plasmid from three different sources was established by the use of restriction-enzyme fingerprinting. The dissemination and persistence of this plasmid in environmental and fecal organisms, despite the disappearance of multiple antibiotic-resistant K. pneumoniae, provided a potential source for spread to other bacteria.

Development of a statewide program for surveillance and reporting of hospital-acquired infections.

In 1974, a statewide program was begun to improve surveillance of nosocomial infection in Virginia hospitals. Infection control practitioners were trained at the University of Virginia Hospital, Charlottesville, and were encouraged to submit monthly surveillance reports for analysis. In the first three years of the project, 141 students from 65 hospitals within the state attended a two-week basic course, with eight to 10 students per class. Of the 98 Virginia hospitals that sent students, 75 (73%) submitted monthly reports. The consistency of reporting (number of monthly reports received divided by the number of possible reporting months) was 83%. The sensitivity of reported data was estimated in comparative daily prospective surveys to be 69% for participating hospitals, and the specificity was 99%. The crude infection rate for the first 1.1 million patients at risk was 3.3%.

Epidemic kepone poisoning in chemical workers.

From March 1974 through July 1975, 76 (56%) of 133 persons who had worked at a pesticide plant that produced Kepone, a chlorinated hydrocarbon insecticide, contracted a previously unrecognized clinical illness characterized by nervousness, tremor, weight loss, opsoclonus, pleuritic and joint pain, and oligospermia. Illness incidence rates for production workers (64%) were significantly higher than for nonproduction personnel (16%). The mean blood Kepone level for workers with illness was 2.53 ppm and for those without disease 0.60 ppm (p less than 0.001). Blood Kepone levels in current workers (mean, 3.12 ppm) were higher than those in former employees (1.22 ppm). Blood Kepone levels for workers in nearby businesses and for residents of a community within 1.6 km of the plant ranged from undetectable to 32.5 ppb. Illness attributable to Kepone was found in two wives of Kepone workers; there was no apparent association between frequency of symptoms and proximity to the plant in the survey of the community population.

PIP: From March 1974-July 1975, 76 (57%) of 133 persons who had worked at a pesticide plant that produced Kepone, a chlorinated hydrocarbon insecticide, contracted a previously unrecognized clinical illness characterized by nervousness, tremor, weight loss, opsoclonus, pleuritic and joint pain, and oligospermia. Illness incidence rates for production workers (64%) were significantly higher than for nonproduction personnel (16%). The mean blood Kepone level for workers with illness was 2.53 ppm and for those without disease 0.60 ppm (p0.001). Blood Kepone levels in current workers (mean, 3.12 ppm) were higher than those in former employees (1.22 ppm). Blood Kepone levels for workers in nearby businesses and for residents of a community within 1.6 km of the plant ranged from undetectable to 32.5 ppb. Illness attributable to Kepone was found in wives of 2 Kepone workers; there was no apparent association between frequency of symptoms and proximity to the plant in the survey of the community population.