Stephen C. Aronoff

Prophylactic antibiotics with intracranial pressure monitors and external ventricular drains: a review of the evidence

BACKGROUND The role of prophylactic antibiotics (PABs) in preventing infections associated with intracranial pressure (ICP) monitors and external ventricular drains (EVD) is not well defined. METHODS This study includes an analysis of published reports and a survey of current practices regarding the use of PABs with ICP monitors and EVDs. A computerized data search and a review of the abstracts from two major national neurosurgical meetings over the past decade yielded 85 related articles. Three independent investigators, blinded to the title, author(s), institution(s), results, and conclusions of the articles used predetermined inclusion criteria to select studies for meta-analysis. Thirty-six responses were returned from 98 questionnaires (37%) mailed to university neurosurgical programs. RESULTS Among the articles reviewed, only two studies met the predetermined inclusion criteria for the meta-analysis, and they were of insufficient size to produce statistically significant results. Among the 36 programs that responded to the survey, 26 (72%) used PABs, mainly cephalosporins (46%) and semisynthetic penicillins (38%), with ICP monitors and EVDs. Twenty-two (85%) used one drug, and 4 (15%) used two drugs. Twenty-two (61%) of the total group reported intra-institutional variation in practices among individual staff neurosurgeons. Nineteen (53%) expressed interest in a retrospective study, and 27 (75%) expressed interest in a prospective study on the role of PABs in minor neurosurgical procedures. CONCLUSION No consensus regarding the use of PABs with ICP monitors and EVDs is noted. Randomized controlled trials of sufficiently large size with appropriate blinding are needed to address this issue.

Multidisciplinary evidence-based medicine journal clubs: curriculum design and participants' reactions.

BACKGROUND Evidence-based medicine (EBM) is becoming an accepted educational paradigm in medical education at a variety of levels. It focuses on identifying the best evidence for medical decision making and applying that evidence to patient care. METHODS Three EBM journal clubs were developed at the West Virginia University School of Medicine. One was for senior medical students, another for residents, and the third for primary care faculty members. In each, the sessions stressed answering clinical questions arising from actual patient-care issues. The curricular structure and development of the journal clubs are described. Participants anonymously evaluated aspects of the journal clubs regarding their educational value with Likert scale questions. RESULTS Faculty members and residents generally gave high evaluations to all aspects of the EBM journal clubs. Student evaluations were more mixed. For each of the evaluation questions, the student means were lower than those of faculty and residents. However the differences reached statistical significance only in the responses to the usefulness of the sessions in understanding the medical literature (P < 0.01). Residents and faculty rated the EBM sessions more favorably than grand rounds or the resident lecture series. CONCLUSIONS The establishment of evidence-based medicine journal clubs is feasible, and learners seem to value the sessions. More developed learners may gain more from the experience than those earlier in their medical education.

Effects of pentoxifylline on sputum neutrophil elastase and pulmonary function in patients with cystic fibrosis : preliminary observations

High concentrations of free human neutrophil elastase in bronchial epithelial fluid are believed to be a major factor in the evolution of pulmonary injury in cystic fibrosis (CF). To test this hypothesis, we studied pentoxifylline, a compound that inhibits tumor necrosis factor alpha transcription and its stimulatory effect on polymorphonuclear neutrophils, in patients with CF who had chronic Pseudomonas bronchitis. Subjects older than 11 years of age randomly received placebo or pentoxifylline (1600 mg/day) orally, in a double-blind fashion, for 6 months. Pulmonary function and sputum elastase concentrations were determined before therapy and bimonthly during therapy; compliance was determined by measuring serum drug concentrations. Of the 16 patients who completed the study, 9 received pentoxifylline. The sputum elastase concentrations among placebo recipients were significantly increased from baseline at 4 and 6 months (F = 3.44; p < 0.05); the values remained unchanged in the treatment group. The mean forced vital capacity for the placebo group decreased from 59.2% +/- 15.4% predicted at baseline to 52.0% +/- 12.9% predicted at 6 months; the values in the treatment group remained largely unchanged. The forced vital capacity improved between baseline and 6 months for four of nine pentoxifylline recipients and none of the seven control patients (p = 0.09). During the study, four of seven placebo recipients experienced a significant pulmonary exacerbation compared with one of nine treated patients (p = 0.077). These findings support the hypothesis that polymorphonuclear neutrophil elastase is a factor in the evolution of CF lung disease; further studies are needed to define the role of pentoxifylline in the treatment of CF.

Decreased baseline beta-lactamase production and inducibility associated with increased piperacillin susceptibility of Pseudomonas cepacia isolated from children with cystic fibrosis.

ABSTRACT: The incidence of pulmonary infections in children with cystic fibrosis caused by Pseudomonas cepacia, an organism which may possess an inducible β-lactamase, has increased since 1978. Seven of 13 sputum isolates of P. cepacia from children with cystic fibrosis were classified as inducible by quantitative enzyme production following preincubation with 100, 200, or 400 µg/ml of cefoxitin. The recovery of inducible strains tended to be associated with recent ceftazidime therapy. Susceptibility to aztreonam, ceftazidime, and piperacillin alone or combined with the β-lactamase inhibitors. YTR 830 or sulbactam, and isoelectric focusing for β-Iactamase were performed. Inducible isolates produced significantly more β-lactamase than noninducible strains with or wihtout the addition of cefoxitin. Noninducible isolates were more susceptible than inducible isolates to 8 µg/ml of piperacillin, a difference that was eliminated with the addition of either β-lactamase inhibitor. Twelve of 13 strains produced a β- lactamase band in the pH range of 7.9-8.1; no differences in satellite patterns were noted between the two groups of organisms. Increased production of β-lactamase in the absence of an inducer may account for piperacillin resistance in P. cepacia in children with cystic fibrosis.

Pseudomonas aeruginosa as a primary pathogen in children with bacterial peritonitis

This prospective study compared the efficacy of sulbactam/ampicillin and clindamycin/gentamicin in the treatment of children with bacterial peritonitis. Of the 29 children enrolled, 17 were evaluable; eight received sulbactam/ampicillin/gentamicin and nine clindamycin/gentamicin. Sixteen patients were previously healthy children with appendicitis. An average of 3.6 bacterial species were recovered from the peritoneal fluid of each patient. E coli and B fragilis were the most common aerobic and anaerobic isolates, recovered from 15 and ten patients, respectively. Pseudomonas aeruginosa was recovered from seven of 17 children; the three children with P aeruginosa infections randomized to the sulbactam/ampicillin group received gentamicin in addition to the investigational agents throughout the treatment course. Although the study groups were small, there was no difference in age, sex, number of pathogens per patient, duration of hospitalization, toxicity, or treatment failures between the two treatment groups or between children infected with P aeruginosa and controls. As a result of the high prevalence of P aeruginosa in the peritoneal exudate of otherwise healthy children with appendicitis, initial antimicrobial therapy in this patient population should include agents effective against this organism.

The effect of exocrine pancreatic function on chloramphenicol pharmacokinetics in patients with cystic fibrosis.

ABSTRACT: The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16–30 yr, with cystic fibrosis. Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-aminobenzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule. In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes. The relative amounts of active chloramphenicol available in systemic circulation was CAP-base ≥ CAP-S ≥ CAP-P. Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation. Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable. Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens. This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement. The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency.

Use of the paraffin wax baiting system for identification of Pseudomonas aeruginosa clinical isolates

Pseudomonas aeruginosa is the primary pathogen among the Pseudomonads and is known for its minimal nutritional requirements, capacity to use paraffin as a sole carbon source, and biofilm formation. Because the ability of Pseudomonads to grow on paraffin is not commonly found among human pathogens and the primary Pseudomonas human pathogen is P. aeruginosa, we studied the adaptation of the paraffin baiting system for the growth and identification of clinical isolates of P. aeruginosa. We also studied the effectiveness of combining a fluorescence assay measuring fluorescein (pyoverdin) production and oxidase test with the paraffin baiting assay for P. aeruginosa speciation. Strains were tested for the capacity to use paraffin as a sole carbon source using the paraffin baiting system with Czapeks minimal salt medium. Of 111 P. aeruginosa clinical isolates tested for using paraffin as a sole carbon source, 45% exhibited growth on paraffin at 24 h and 76.6% exhibited growth on paraffin at 48 h. The ability of the reference strains and clinical isolates were then tested for their ability to associate with the paraffin slide in the presence of an additional carbon source. Of 111 P. aeruginosa clinical isolates tested, 85 strains (76.6%), and 102 (93%) were associated with the paraffin surface at 24 and 48 h. We successfully combined fluorescence and oxidase assays with the paraffin baiting system for identification of P. aeruginosa. The simple and inexpensive paraffin baiting system is a useful method for the identification and study of P. aeruginosa suitable for both the clinical and research laboratory.

Systematic Review and Meta-analysis of Seizure Recurrence After a First Unprovoked Seizure in 815 Neurologically and Developmentally Normal Children

Limited data exist for health care providers regarding seizure recurrence after a first unprovoked seizure in previously neurologically and developmentally normal children. A systematic review and meta-analysis was conducted to assess seizure recurrence after a first unprovoked seizure by performing an electronic search in PubMed, Embase, and Scopus. Six studies from 2817 met the inclusion criteria. The sample size consisted of 815 neurologically and developmentally normal children (1 month–17.5 years) on no antiepileptic drugs. This systematic review and meta-analysis estimated a recurrence rate within 3 years of 45% (95% CI: 37%, 60%). This estimate provides a touchstone for health care providers who are managing this particular population of children.

MODULATION OF CHLORAMPHENICOL(C) BIOAVAILABILITY(F) BY PANCREATIC ENZYME REPLACEMENT (PRE) IN CYSTIC FIBROSIS (CF)

The effect of PER on the F of C was ascertained in 5 adolescent: patients with CF. Each patient was studied on 6 occasions separated by at least 24 hours. Exocrine pancreatic function was ascertained by the urinary excretion of PABA following ingestion of N-benzoyl-L-tyrosyl PABA. C was administered as C succinate(CS) intravenously, and C palmitate(CP) or C base (CB) orally at a dose of 20mg/kg with or without PER. Multiple timed blood samples were obtained over a 12 hour period following each dose and analyzed by HPLC. Model independent pharmacokinetic analysis of CS biodis-position revealed ([xmacr ;[plusmn;SD) t½, 3.35±1.16hr; Vdss,1.39± 0.49 4kg; and Clp, 267.33±53.96ml/min/1.73m2. These values were comparable to those obtained with CB and for CS in unaffected individuals. The absolute F of CB ranged from 71-154% without PER and increased by 8-17% after PER. For CP the absolute F ranged from 21-59% increasing by 2-200% following PER. In one patient CP absorption continued throughout the monitoring period after PER. The wide range of effect of PER on the F of the oral formulations of C appeared related to the level of intrinsic exocrine pancreatic function.The relative F, CP/CB, was directly related to urinary PABA excretion (r=0.9). These results suggest that PER may significantly enhance the F of CP through replacement of pancreatic lipase. Pancreatic enzymes may play a role in enhancing the F of CB as well.

Evaluation of latamoxef as initial therapy of bone and joint infections in childhood.

The efficacy and pharmacokinetics of latamoxef were evaluated during initial therapy of bacteriologically proven bone and joint infections in children. Pharmacokinetic evaluation revealed no significant difference in latamoxef biodisposition after the first dose or at steady state. Peak serum concentrations exceeded 140 mg/l and 8-hour trough concentrations averaged 6.5 mg/l. The patients were infected with a variety of gram-positive and gram-negative pathogens. All were sensitive to readily achievable serum concentrations of latamoxef; moreover, the serum concentration remained above the MIC of the most resistant organism for at least 7 h after each dose. All patients responded favorably to initial therapy and there have been no relapses in more than 2 years of clinical follow-up.