Sequential peripartum herpes simplex virus type 2 disease in parents and their newborn mimicking intrafamily spread of common viruses.

Herpes simplex type 2 (HSV2) disease developed sequentially among two parents and their newborn. The father first became ill with upper-respiratory symptoms and fever. Then, 5 days later, shortly after delivery, the mother had fever, pharyngitis, and diarrhea. Subsequently, the infant developed undifferentiated febrile illness at the age of 3 days. HSV etiology was recognized by incidental isolation of HSV2 from the newborn naospharynx. The father never developed genital lesions and the mother's symptoms remained nonspecific for several days prior to the onset of genital manifestations. The sequential emergence and manifestations of these infections could have been misconstrued for an intrafamily spread of respiratory or enteric viruses. This cluster illustrates that HSV2 may cause sequential symptomatic disease in susceptible individuals mimicking other viruses.

Clustering of Candida infections in the neonatal intensive care unit: concurrent emergence of multiple strains simulating intermittent outbreaks.

BACKGROUND: Clusters of Candida albicans and Candida parapsilosis infections were noted intermittently in our neonatal intensive care unit (NICU). We attempted to determine whether these clusters represented single strain outbreaks or coincidental emergence of unrelated strains. METHODS: A retrospective examination of the frequency of candidemia during a 9-year period, two point prevalence studies of colonization and assessment of strain relatedness of individual infant isolates during and in between clusters during a 2-year period with karyotyping and restriction endonuclease analysis of genomic DNA (REAG). RESULTS: C. albicans and C. parapsilosis infections emerged in a scattered pattern (1 to 2 cases every few months) with intermittent clustering of 3 cases/month. The colonization rate was 50% 5 weeks after an apparent cluster, equally distributed between C. albicans and C. parapsilosis, and 17.6% (exclusively with C. parapsilosis) 4 months after absence of invasive disease. Utilizing REAG or karyotyping singly we noted 12 and 16 DNA banding patterns, respectively, among 23 infant isolates. Few patterns were observed repeatedly over 2- to 20-month periods, implying recurrent emergence of the same strains. Combining karyotyping with REAG revealed a different epidemiologic pattern. It identified 20 distinct composites with identical composites in 3 infant pairs. All infants with identical composites were in the NICU concurrently. The frequency of strain relatedness was comparable among clustered cases (16.7%), scattered cases (7.7%) and simultaneously colonized infants (16.7%). CONCLUSIONS: These findings illustrate that Candida infections clustered periodically in our NICU but that these clusters were often caused by unrelated strains with infrequent cross-infection during and between clusters. With suboptimal typing this pattern of emergence can be mistaken for same strain outbreaks.

Severe psittacosis during pregnancy and suppression of antibody response with early therapy.

A cluster of 3 cases of psittacosis occurred among members of one family. The initial case was a pregnant woman who presented with extensive multilobar infiltrates and severe respiratory distress necessitating mechanical ventilation. Her respiratory failure worsened during 36 h of erythromycin therapy. Improvement coincided with the termination of pregnancy and the initiation of doxycycline treatment. The remaining patients developed milder illness. Serologic assessment of the affected subjects suggests that early treatment may suppress antibody response.

Candidemia: current epidemiologic characteristics and a long-term follow-up of the survivors.

All consecutive patients with positive blood culture for Candida species over a 6-year period were evaluated to define recent epidemiologic characteristics of candidemia, and to assess the prevalence of late complications. We encountered 106 cases; medical records were available for 99 of them. The rate of candidemia was increasing until 1990, after which it declined. C. albicans was the most common species, but in the last 2 years, C. tropicalis and C. parapsilosis were emerging. Overall mortality rate was 54.5% without significant variation during the study period. Antifungal therapy was withheld in 24/99 cases (24.2%). Decision to withhold treatment was taken in 19/59 cases (32.2%) before the availability of fluconazole in 1990, compared with 5/40 cases (12.5%) afterward (p < 0.05). Follow-up was possible in 35 instances for an average period of 17.1 months (range: 1-48 months); 7 of these individuals, all with transient candidemia, were untreated. None of the survivors developed late complications. These findings demonstrate that candidemia appears to be declining since 1990, with a noticeable decrease in the prevalence of C. albicans but an increase in that of C. tropicalis and C. parapsilosis, that fewer patients are left untreated since fluconazole became available, and that the risk of late complications among the survivors is low.

A case of Behcet's disease with intestinal involvement due to Crohn's disease.

A 15-yr-old, Arabic male presented with painful, recurrent, self-resolving oral and genital ulcers, erythema nodosum and uveitis. Behcet's disease was diagnosed. A few months later, he experienced anorexia, abdominal pain, diarrhea, and weight loss. Although all routine laboratory and radiologic investigations were negative, colonoscopy revealed the presence of serpiginous ulcers with pseudopolyps and inflamed intervening mucosa in the proximal half of the colon. Therapy with oral steroids was helpful, but the disease exacerbated a few months after prednisone was discontinued. Repeat evaluation showed similar endoscopic findings and, on colonic biopsy, noncaseating granulomas compatible with Crohn's disease were seen. Again, the patient responded well to oral steroids and sulfasalazine. We believe that gastrointestinal involvement in our patient is compatible with Crohn's disease and that screening tests to rule out chronic inflammatory bowel disease should be performed in the presence of gastrointestinal involvement in Behcet's disease. Behcet's disease may be a part of the spectrum of chronic inflammatory bowel disease.

Acute hematogenous osteomyelitis in children.

Sixty-nine children with acute hematogenous osteomyelitis were studied retrospectively. All were treated with antibiotics, and eight underwent fenestration osteotomies. In the operatively treated group, three poor results occurred. In a more recent prospective study of 44 patients, drainage was undertaken only when pus was aspirated. All results were good or excellent. We recommend operative drainage only when a demonstrated abscess is found by aspiration.

Cefotaxime diffusion into cerebrospinal fluid of children with meningitis.

Cefotaxime diffused consistently and in therapeutic levels into the cerebrospinal fluid (CSF) of 13 children successfully treated for bacterial meningitis. CSF cefotaxime levels early (6.0 micrograms/ml) and late (1.2 micrograms/ml) in treatment were severalfold the MBCs for the infecting organisms. After a single 40-mg/kg dose to each of five infants with ventriculostomies, mean CSF levels of cefotaxime were 6.4, 5.7, and 4.5 micrograms/ml at 2, 4, and 6 h, respectively.

Efficacy and safety of ceforanide in the treatment of childhood infections.

Fifty-seven children, ages 1 month to 17 years, were treated with parenteral ceforanide. Most patients received 20 mg/kg of the drug intramuscularly every 12 hours. The mean duration of ceforanide therapy was 6.3 days (range, 3 to 14 days). Because ceforanide has a relatively long half-life of 1.94 +/- 0.43 hours (range, 1.1 to 3.3 hours), suprainhibitory plasma concentrations against most pathogens recovered from the study patients were maintained for 8 to 12 hours after a dose. Ceforanide diffused well into abscess cavities and joint fluid. Initial clinical response was satisfactory in all patients; however, one patient with Haemophilus influenzae type b bacteremia had relapse of bacteremia one week after ceforanide therapy. Ceforanide was well-tolerated with minimal pain at the site of intramuscular injections. Other side effects were minor and transient.

Pharmacokinetics of intravenously administered piperacillin in preadolescent children.

We studied the pharmacokinetics of piperacillin in 37 preadolescent children (mean age 52 months, range 1 month to 11 years) after 50 mg/kg IV doses. Pharmacokinetic parameters were determined after the initial dose in 18 instances and after subsequent doses in 32 instances. There were no significant differences between the initial doses and the subsequent doses in the plasma piperacillin concentrations at comparable times, the elimination rate constants, the elimination-phase plasma half-lives, the total body clearances, the apparent volumes of distribution, or the areas under the concentration curves. At the end of a 30-minute infusion of the drug, the plasma concentration was 166.2 +/- 42.2 mg/L (mean +/- SD) and ranged from 91.6 to 268.3 mg/L. The mean half-life was 31.0 +/- 9.4 minutes. The half-life of piperacillin in children 1 to 6 months of age (47.2 minutes) was significantly longer than in older children (28.8 minutes) (P less than 0.05). Likewise, the total body clearance of the drug in the younger age group (71.7 ml/min/m2) was significantly lower than in the older children (130.8 ml/min/m2) (P less than 0.05). The mean renal clearance of the drug was only 63% (range 39% to 85%) of the total body clearance, suggesting a variable but substantial nonrenal route of elimination. The intravenous administration of 50 mg/kg piperacillin every four hours results in adequate plasma concentrations for the treatment of most infections caused by gram-negative and gram-positive organisms.

Pharmacokinetics of intramuscular ceforanide in infants, children, and adolescents.

We studied the pharmacokinetics of intramuscular ceforanide in 46 infants, children, and adolescents, ranging in age from 1 month to 17 years. After the subjects were given 20-mg doses of ceforanide per kg, the mean peak plasma concentration was 56.3 microgram/ml (range, 27.0 to 95.0), the mean 8-h level was 5.9 microgram/ml (range, 1.5 to 13.5), and the mean 12-h level was 1.5 microgram/ml (range, 0.2 to 4.2). Ceforanide half-life varied with the ages of the patients: in 1- to 2-year-old children, in half-life was significantly shorter (1.5 h) than in younger or older children. Plasma concentrations at 8 and 12 h after a dose were lowest in 1- to 2-year-old children. There was no relationship between the area under the curve, the volume of distribution, or the body clearance of ceforanide to the ages of the patients. Within 6 h of administration of the drug, a mean of 77.5% of a dose was excreted in urine, and at the end of 12 h, virtually all (93.9%) of the administered dose was recovered in urine samples. The administration of ceforanide every 12 h did not result in drug accumulation. A dose of 20 mg of ceforanide per kg every 12 h is recommended for most pediatric patients. Dosage recommendations for 1- to 2 year-old children are presented.

Relative bioavailability of intravenous chloramphenicol succinate and oral chloramphenicol palmitate in infants and children.

The relative bioavailability of intravenously administered chloramphenicol succinate and orally administered chloramphenicol palmitate was compared in 18 children, age 2 months to 14 years. The area under the serum concentration vs time curve of chloramphenicol and urinary excretion of chloramphenicol succinate were determined in each child under steady-state conditions while receiving chloramphenicol succinate and again while receiving chloramphenicol palmitate. The mean AUC was significantly greater during oral therapy compared to intravenous therapy (110 vs 78 mg hr/L, P less than 0.001). The relative bioavailability of chloramphenicol succinate was 70% compared to chloramphenicol palmitate. This could be explained by the mean loss of 36% of the intravenous dose in the urine as unhydrolyzed chloramphenicol succinate. The intravenous dose of chloramphenicol succinate did not correlate with AUC (r = 0.193). However, there was a significant correlation between the oral dose of chloramphenicol palmitate and AUC (r = 0.429, P = 0.025). The bioavailability of orally administered chloramphenicol palmitate is superior to that of chloramphenicol succinate given intravenously. Furthermore, there is a greater correlation between dose and amount of active drug in the body when the oral preparation is used. Oral administration of chloramphenicol palmitate appears to offer significant therapeutic advantages in patients who can tolerate medication given orally.

Diffusion of moxalactam into the cerebrospinal fluid in children with bacterial meningitis.

We studied the penetration of moxalactam into the cerebrospinal fluid of 16 children (age range one month to 4 1/2 years) who were being treated for bacterial meningitis. Two hours after single intravenous doses of 15 or 25 mg/kg, moxalactam was detectable in the CSF in only one of 11 instances; however, following three doses (50 mg/kg each) moxalactam was detectable in eight of 17 instances. In these eight instances CSF concentrations of moxalactam ranged between 1.5 and 18.9 micrograms/ml (mean 7.7) and the CSF/plasma ratio ranged from 2.6 to 36% (mean 17.7). There was no relation between the stage of meningitis or the CSF cell count and the diffusion of the drug into the CSF. However, the diffusion of the drug significantly correlated with the CSF protein content. In view of the unpredictability of moxalactam penetration into CSF, caution should be exercised in using it alone in the treatment of meningitis.

Susceptibility of Haemophilus influenzae to chloramphenicol and eight beta-lactam antibiotics.

We examined the minimal inhibitory concentrations and minimal bactericidal concentrations of chloramphenicol, ampicillin, ticarcillin, cefamandole, cefazolin, cefoxitin, cefotaxime, ceforanide, and moxalactam for 100 isolates of Haemophilus influenzae, 25 of which produced beta-lactamase. Susceptibility was not influenced by the capsular characteristic of the organism. The mean minimal inhibitory concentrations of cefamandole, ticarcillin, and ampicillin for beta-lactamase-producing strains were 3-, 120-, and 400-fold higher than their respective mean minimal inhibitory concentrations for beta-lactamase-negative strains. No such difference was noted for the other antibiotics. We performed time-kill curve studies, using chloramphenicol, ampicillin, cefamandole, cefotaxime, and moxalactam with two concentrations of the antimicrobial agents (4 or 20 times the minimal inhibitory concentrations) and two inoculum sizes (10(4) or 10(6) colony-forming units per ml). The inoculum size had no appreciable effect on the rate of killing of beta-lactamase-negative strains. The rates at which beta-lactamase-producing strains were killed by chloramphenicol, cefotaxime, and moxalactam was not influenced by the inoculum size. Whereas cefamandole in high concentrations was able to kill at 10(6) colony-forming units/ml of inoculum, it had only a temporary inhibiting effect at low drug concentrations. Methicillin and the beta-lactamase inhibitor CP-45,899 were able to neutralize the inactivation of cefamandole by a large inoculum of beta-lactamase-producing H. influenzae.

Pharmacology, Safety, and efficacy of cefamandole in childhood infections.

We used cefamandole in the initial treatment of 34 children (10 months to 15 years of age) with suspected bone, joint, or soft tissue infections. The minimal inhibitory concentration of organisms encountered ranged between 0.015 and 2 microgram/ml. At 1 h after intravenous infusion of 25 mg/kg, the mean serum level of cefamandole was 26.2 microgram/ml (range, 8.9 to 47.5 microgram/ml), and at 3 h the level was 1.8 microgram/ml (range, 0.6 to 4.4 microgram/ml), which is above the minimal inhibitory concentration for most of the organisms encountered. However, when the drug was given intravenously every 6 h, the mean level after a 37-mg/kg dose was 0.9 microgram/ml (range, less than 0.5 to 1.9 microgram/ml) at 4 h and, by extrapolation, would have fallen below 0.1 microgram/ml at 6 h. The mean serum half-life was 34 min. Cefamandole appeared to diffuse well into synovial fluid, with joint fluid levels between 5 and 40 microgram/ml. The drug was tolerated well. Cefamandole appears to be a reasonable alternative in the initial treatment of skeletal infections in children, but need to be administered every 4 h to maintain suprainhibitory serum levels between doses.

Pharmacokinetic and clinical evaluation of moxalactam in infants and children.

37 patients ranging in age from 9 months to 14 years, with various infections, were treated with moxalactam. The pharmacokinetics of the drug were studied in 18 patients. The mean plasma concentration 1 h after a 25 mg/kg intravenous dose was 41.4 micrograms/ml +/- 15.6 SD, the half-life was 1.5 h +/- 0.4 SD and the mean Vd was 550 ml/kg +/- 239 SD. The total body clearance of moxalactam was 4.1 ml/min/kg +/- 1.5 SD and the mean renal clearance 4.5 ml/min/kg +/- 2.8 SD. Between 52 and 107% of the administered dose was recovered in the urine within 8 h after administration. The pharmacokinetics after the first and multiple doses of moxalactam were similar, indicating no accumulation of the drug with repeated administration. The clinical response was adequate in 35 of 37 patients. Moxalactam was well tolerated and only minor and transient hematological abnormalities were observed.