Infection and risk of ischemic stroke: differences among stroke subtypes.

BACKGROUND AND PURPOSE: Although prior studies have demonstrated that 25% to 35% of stroke patients have had a recent infection, the role of infection as a risk factor remains unclear. Our aim was to characterize the effect of infectious/inflammatory syndromes on stroke risk. METHODS: Case-control and crossover analyses of 233 cases and 363 controls aged 21 to 89 years were performed. Cases were patients hospitalized with a first ischemic stroke at a Los Angeles, California, medical center. Controls were outpatients in the hypertension, diabetes, and general medical clinics. All subjects were administered a neurological examination, an infection/inflammation (I/I) examination, and an interview to elicit recent I/I history at baseline (within several days of stroke onset) and again approximately 2 months later. Three physicians classified subjects by the presence or absence of I/I within 1 month of the index dates, based on findings of the I/I examination, the interview report, and laboratory results. RESULTS: Infections, either total or specific, were not found more frequently in cases than controls. However, patients with a recent respiratory tract infection suffered more often from large-vessel atherothromboembolic or cardioembolic stroke than did patients without infection (48% vs 24%, P=0.07). The age- and sex-adjusted relative risk estimate for these subtypes was 1.75 (95% CI, 0.86 to 3.55). The risk was notably high for those without stroke risk factors: 4.15 (95% CI, 1.22 to 14.1) for normotensives, 2.71 (95% CI, 1.04 to 7.06) for nondiabetics, and 1.74 (95% CI, 0.74 to 4.07) for nonsmokers. Patients with a recent respiratory infection also had a more severe neurological deficit on admission than those without infection (P=0.05). CONCLUSIONS: Our results suggest that respiratory tract infection may act as a trigger and increase the risk of large-vessel and/or cardioembolic ischemic stroke, especially in those without vascular risk factors.

In vitro activities of nontraditional antimicrobials against multiresistant Acinetobacter baumannii strains isolated in an intensive care unit outbreak.

Fifteen multiresistant Acinetobacter baumannii isolates from patients in intensive care units and 14 nonoutbreak strains were tested to determine in vitro activities of nontraditional antimicrobials, including cefepime, meropenem, netilmicin, azithromycin, doxycycline, rifampin, sulbactam, and trovafloxacin. The latter five drugs were further tested against four of the strains for bactericidal or bacteriostatic activity by performing kill-curve studies at 0.5, 1, 2, and 4 times their MICs. In addition, novel combinations of drugs with sulbactam were examined for synergistic interactions by using a checkerboard configuration. MICs at which 90% of the isolates tested were inhibited for antimicrobials showing activity against the multiresistant A. baumannii strains were as follows (in parentheses): doxycycline (1 microg/ml), azithromycin (4 microg/ml), netilmicin (1 microg/ml), rifampin (8 microg/ml), polymyxin (0.8 U/ml), meropenem (4 microg/ml), trovafloxacin (4 microg/ml), and sulbactam (8 microg/ml). In the kill-curve studies, azithromycin and rifampin were rapidly bactericidal while sulbactam was more slowly bactericidal. Trovafloxacin and doxycycline were bacteriostatic. None of the antimicrobials tested were bactericidal against all strains tested. The synergy studies demonstrated that the combinations of sulbactam with azithromycin, rifampin, doxycycline, or trovafloxacin were generally additive or indifferent.

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

Meropenem versus tobramycin with clindamycin in the antibiotic management of patients with advanced appendicitis.

BACKGROUND: Meropenem (MP), a new carbapenem antibiotic, has excellent antimicrobial activity against the enteric flora commonly encountered in acute appendicitis. Although similar to imipenem, it may have clinical advantages. STUDY DESIGN: We compared patients with advanced appendicitis (gangrenous or perforated) treated with 1,000 mg MP every eight hours with those given the combination of tobramycin 5 mg/kg/day at eight hour intervals and clindamycin 900 mg every eight hours. Both treatments were given intravenously. Patients were randomized to either group of the double-blind study. RESULTS: Of 129 evaluable cases, 63 received MP and 66 received both tobramycin and clindamycin (T/C). The two groups were similar in age, sex, and severity of disease. The mean number of days of postoperative fever (MP = 3.1 +/- 1.7 SD compared to T/C = 4.4 +/- 2.2 SD, p < or = 0.01), days of antibiotic therapy (MP = 6.1 +/- 1.6 SD compared to T/C = 7.3 +/- 2.2 SD, p = 0.01), and therefore hospital stay (MP = 8.0 +/- 3.5 SD compared to T/C = 9.4 +/- 2.6 SD, p < 0.01) were significantly better for patients treated with MP. No difference was found between the numbers of failures in each group (MP = 5 compared to T/C = 6). CONCLUSIONS: This study demonstrates a small but significant reduction (approximately one day) in post-operative fever, duration of antibiotic treatment, and hospital stay for patients treated with MP compared to those treated with T/C.

Unrecognized HIV-1 infection in inner-city hospital emergency department patients.

To determine the prevalence of unrecognized human immunodeficiency virus (HIV)-1 infections in patients presenting to an inner-city hospital emergency department, medical records were reviewed from 1,945 patients diagnosed with diseases not related to HIV or acquired immunodeficiency syndrome. The overall seroprevalence was 2.1% (40): 1.8% (11) in nontrauma versus 3.0% (29) in trauma patients. The highest prevalence was found in black, male, uninsured patients.

University of Southern California Repeatable Episodic Memory Test.

The University of Southern California Repeatable Episodic Memory Test (USC-REMT) was developed to provide a brief assay of memory in clinical drug trials where the same subject is tested multiple times over days or weeks. Therefore, it had to be minimally affected by repeated testing. The test also provides a measure of subjective organization, a cognitive strategy that might be sensitive to frontal lobe dysfunction and HIV-related memory deficits. The USC-REMT has seven different lists, each composed of 15 semantically unrelated, high-frequency nouns. The words are presented in a different order on three study-test trials. After each study trial the subject recalls the words in any order. The test takes about 10 min to administer and score. The recall protocol can be scored for (a) global mnemonic efficiency, (b) primary and secondary memory, (c) subjective organization, (d) recall consistency and (e) recall as a function of serial position. We report initial data showing that the test is sensitive to memory decrements. Thirty-six HIV-1 seropositive men, at various stages of illness, recalled significantly fewer words and exhibited less subjective organization than 14 matched controls. The test had no significant practice effects over the first three administrations when separated by several days. The seven alternate lists are essentially equivalent. The USC-REMT appears to complement currently published verbal memory tasks.

Pharmacoeconomics of piperacillin/tazobactam and imipenem/cilastatin in the treatment of patients with intra-abdominal infections.

Costs involved in using piperacillin 4 g/tazobactam 500 mg, given as intermittent intravenous infusions every 8 hours, were compared with those for imipenem/cilastatin 500 mg, given as intermittent intravenous infusions every 6 hours, for the treatment of patients with gangrenous or perforated appendicitis. A total of 88 patients were included in our cost analyses: 42 patients in the piperacillin/tazobactam group and 46 patients in the imipenem/cilastatin group. Durations (mean +/- SD) of antibiotic therapies were 7.8 +/- 3.3 days and 7.1 +/- 2.6 days for the piperacillin/tazobactam and imipenem/cilastatin groups, respectively. No statistical significance was found for the difference in duration of therapy (P = 0.376). Total drug treatment costs were $538.83 +/- $385.33 for the piperacillin/tazobactam group and $687.66 +/- $345.37 for the imipenem/cilastatin group. This difference in treatment cost was statistically significant (P = 0.0001). The need for laboratory tests and the use of other medications were not different between the two groups. Total hospital-days charges were higher for the piperacillin/tazobactam group ($18,339.76 +/- $6090.38) compared with the imipenem/cilastatin group ($16,150.00 +/- $5088.60) (P = 0.052). These findings suggest that length of hospital stay should be the economic focus of antibiotic therapy.

Fungemia and colonization with nystatin-resistant Candida rugosa in a burn unit.

Yeast isolates from burned patients were analyzed retrospectively for a 7-year period (1984-1991). Topical nystatin was used routinely in the burn wound dressing as antifungal therapy beginning in July 1986. Nystatin used was associated with a significant decrease in overall yeast acquisitions in burn wounds; yeasts were isolated from 15.5% of admitted patients before the use of nystatin vs. 10.5% with use of nystatin (odds ratio [OR] = 0.64; 95% confidence interval [CI], 0.48-0.86). New acquisitions of Candida rugosa in burn wounds increased from 0.36% of admissions during the period July 1984 to June 1986 (before nystatin use) to 5.25% in the period July 1986 to June 1991 (during use of nystatin) (OR = 15.3; 95% CI, 4.1-128). The incidence of fungemia decreased from 3.25% of admissions in the pre-nystatin period to 1.43% in the postnystatin period (OR = 0.43; 95% CI, 0.22-0.87). C. rugosa caused none of 18 fungemias in the former period and 15 of 21 in the latter period (P = .002). Susceptibility testing of recent C. rugosa isolates demonstrated resistance to nystatin and moderate susceptibility to amphotericin B and fluconazole. Topical nystatin use was associated with a decrease in fungemias and acquisition of yeasts in burn wounds but with an increase in colonization and fungemias caused by nystatin-resistant, amphotericin B-susceptible C. rugosa.

Pharmacokinetics of meropenem in patients with intra-abdominal infections.

Noncompartmental and compartmental analyses of meropenem disposition in patients receiving 1-g intravenous intermittent infusions every 8 h were performed. Twelve patients (one woman and 11 men) participated in the meropenem pharmacokinetic analysis. Operative findings included perforated appendicitis (five patients), gangrenous appendicitis (five patients), peri-appendical abscess (one patient), and gunshot wound to the abdomen (one patient). The most common associated adverse drug reactions to meropenem were diarrhea and increased liver enzymes. The estimated noncompartmental pharmacokinetic parameters, mean +/- standard deviation, are as follows: maximum drug concentration in plasma, 47.58 +/- 17.59 micrograms/ml; half-life, 1.04 +/- 0.19 h; elimination rate constant, 0.68 +/- 0.12 h-1; area under the concentration-time curve from 0 h to infinity, 57.5 +/- 20.12 micrograms x ml/h; total plasma clearance, 315.40 +/- 71.94 ml/min; renal clearance, 136.7 +/- 89.20 ml/min; volume of distribution at steady state, 26.68 +/- 6.88 liters; and mean residence time, 1.47 +/- 0.28 h. The two-compartment model best described meropenem disposition in our patients. Our findings differed from estimates for healthy volunteers possibly because of the physiologic changes as a result of surgery. Our findings suggest that meropenem (1,000 mg) administered intravenously every 8 h provides adequate concentrations for most intra-abdominal infections.

Prospective randomized study of two different doses of clindamycin admixed with gentamicin in the management of perforated appendicitis.

Septic complications after surgery for enterogenous peritonitis are minimized by adjuvant antibiotics effective against aerobes and anaerobes. Historically, "gold standard" therapy included an aminoglycoside plus clindamycin, the latter given at 600 mg intravenous piggyback (IVPB), every 6 hours. Clindamycin pharmacokinetics suggests that it can be given q8h and admixed with gentamicin, thereby markedly reducing the cost of administration. Although this is now common practice, there is no prospective study comparing the efficacy of the two dose schedules in peritonitis. This study was designed to test the hypothesis regarding the clinical efficacy of the two regimens. One hundred twenty-six patients with gangrenous (n = 34) or perforated appendicitis (n = 91) were randomized (2:1) to receive gentamicin admixed with clindamycin 900 mg IVPB every 8 hours (Group I n = 80) or gentamicin IVPB q8h plus clindamycin 600 mg IVPB every 6 hours (Group II n = 46). Appendectomy was performed, and aerobic and anaerobic cultures were obtained. Twenty-one patients had simultaneous determinations of clindamycin levels in plasma, peritoneal fluid, and appendix. Outcome analysis revealed no significant differences in postoperative days of fever, days non per os, antibiotic therapy, or hospitalization. There were 6 failures (4 abscesses and 2 wound infections) in Group I and 4 failures (1 abscess and 3 wound infections) in Group II. Both antibiotic regimens provided clinically equivalent results in mixed infections due to aerobic and anaerobic bacteria. The admixed clindamycin, administered every 8 hours, results in at least 20% reduction in costs. This is an important consideration.

A clinical comparison of cefepime and metronidazole versus gentamicin and clindamycin in the antibiotic management of surgically treated advanced appendicitis.

Many antibiotics and antibiotic combinations are used for the treatment of peritonitis because of advanced (gangrenous or perforated) appendicitis. An aminoglycoside combined with an antianaerobe antibiotic is one standard treatment, but there is concern about the potential nephrotoxicity of the aminoglycoside and the necessity for monitoring aminoglycoside blood levels. Cefepime, a new broad-spectrum cephalosporin with a prolonged serum half-life, has excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its spectrum of activity is similar to the aminoglycosides, but it has less potential for inducing renal injury. A double-blind, randomized study compared cefepime, 2 grams every 12 hours IVPB plus metronidazole 0.5 grams every eight hours IVPB (C/M) with gentamicin 1.5 milligrams per kilograms of IVPB plus clindamycin 0.9 grams q eight hours IVPB (G/C), administered up to 14 days, in 96 surgically treated patients with gangrenous or perforated appendicitis. Fifty patients had advanced appendicitis (nine gangrenous and 41 perforated) in the C/M group and 46 patients (six gangrenous and 40 perforated) in the G/C group. The mean number of days of postoperative fever (C/M, 4.4 +/- 2.7 versus G/C, 5.0 +/- 2.2), postoperative hospitalization (C/M, 2.0 +/- 1.9 versus G/C, 2.0 +/- 2.1) and antibiotic therapy (C/M, 6.3 +/- 1.9 versus G/C, 6.9 +/- 1.9) was similar in the two treatment groups. There were 11 treatment failures (C/M, three; G/C, eight; p = 0.13), six of which were probably a result of enterococci. No deaths occurred. Our study results show that the efficacy of cefepime plus metronidazole is equivalent to that of clindamycin plus gentamicin.

A randomized study of cefepime versus the combination of gentamicin and mezlocillin as an adjunct to surgical treatment in patients with acute cholecystitis.

In patients with acute cholecystitis, antibiotics are used as an adjunct to cholecystectomy to reduce the incidence of postoperative septic complications thought to be related to bactibilia. Combinations of penicillins, or cephalosporins or aminoglycosides, or both, are often used. Cefepime is a fourth-generation cephalosporin with excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas species. It has a prolonged serum half-life, allowing twice-daily dosing, and is not nephrotoxic. This study was undertaken to determine whether or not cefepime was as effective as the combination of gentamicin and mezlocillin in patients with acute cholecystitis. One hundred and forty-nine patients were randomized, two to one, to receive cefepime or gentamicin and mezlocillin. Cefepime was given intravenously at 2 grams every 12 hours; gentamicin, 1.0 to 1.5 milligrams per kilograms every eight hours, and mezlocillin, 3 to 4 grams every four to six hours. All patients underwent cholecystectomy. Bile cultures were obtained, and concentrations of cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a subset of patients. There were 56 evaluable cefepime-treated and 34 evaluable gentamicin and mezlocillin-treated patients. Bactibilia was present in 17 of 56 cefepime-treated patients (30.4 percent) and ten of 34 gentamicin and mezlocillin-treated patients (29.4 percent). Enterococci were recovered in six cefepime-treated patients. Clinical and bacteriologic responses were similar for the cefepime-treated and gentamicin and mezlocillin-treated groups, with one failure in each group, a wound infection in a patient receiving cefepime and a subhepatic abscess in a patients receiving gentamicin and mezlocillin. Other measures of outcome, such as the number of days of fever, days nothing by mouth, days of hospitalization and days of antibiotic therapy were similar in both groups. Cefepime, with every 12 hour dosing, achieved extremely high concentrations in all tissues assayed at the time of the operation, a mean of eight hours after administration. Adverse clinical events were similar in both treatment groups. Cefepime is as effective as gentamicin and mezlocillin in preventing septic complications after cholecystectomy for acute cholecystitis. Cefepime requires fewer doses, does not require drug monitoring, is not associated with nephrotoxicity and may therefore prove to be a cost-effective alternative to combination therapy that uses an aminoglycoside.

Tissue concentrations of cefepime in acute cholecystitis patients.

Cefepime is a new broad-spectrum cephalosporin with activity against Staphylococcus, Streptococcus, Pseudomonas, and the Enterobacteriaceae. The purpose of this study was to measure cefepime concentrations in plasma, peritoneal fluid, bile fluid and appendix tissue in patients undergoing elective cholecystectomy. Patients were randomly assigned to receive either cefepime, 2 g intravenously in phosphate buffer (IVPB) q 12 h or gentamicin 1.5 mg/kg IVPB q 8 h plus mezlocillin 4 g IVPB q 6 h. During surgery, gall bladder tissue, plasma, peritoneal fluid, and bile fluid samples were obtained at approximately the same time. Thirty-three patients had data acceptable for analysis. Values are given as mean +/- standard deviation. The mean delta time (defined as the time between the administration of cefepime and the time the samples were obtained) was 8.58 +/- 3.53 h. The values for plasma, peritoneal fluid, bile fluid, and gall bladder tissue concentrations were 7.63 +/- 14.17 micrograms/ml, 5.66 +/- 6.80 micrograms/ml, 15.51 +/- 16.94 micrograms/ml, and 5.36 +/- 6.57 micrograms/gm, respectively. The peritoneal fluid/plasma ratio was 2.10 +/- 2.33, the bile fluid/plasma ratio was 14.44 +/- 31.99, and the gall bladder tissue/plasma ratio was 1.44 +/- 1.82. There was a significant correlation between peritoneal fluid and plasma concentration (r = 0.91, p less than 0.0005), and gall bladder tissue and plasma concentration (r = 0.90, p less than 0.0005). There was no correlation between bile fluid and plasma cefepime concentrations. The minimum inhibitory concentration (MIC) data from previous in vitro studies indicate that cefepime concentrations achieved in this patient population would be adequate against typical biliary tract pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Eflornithine treatment of refractory Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.

Eflornithine was offered as compassionate treatment of 33 episodes of Pneumocystis carinii pneumonia in 31 patients with acquired immunodeficiency syndrome who were intolerant of and/or unresponsive to conventional trimethoprim-sulfamethoxazole or pentamidine therapy. A full course of eflornithine consisted of ten days at 400 mg/kg/d but no more than 30 g/d in four divided intravenous doses, four days at 300 mg/kg/d in four divided intravenous doses, and then up to six weeks at 300 mg/kg/d in four divided oral doses where tolerated. Of 33 patient-episodes, 15 patients were discharged from the hospital without need for supplemental oxygen after receiving ten or more days of parenteral therapy and were classified as responders. Of the 16 episodes classified as treatment failures, death occurred within the first 10 days of therapy in 12, and supplemental oxygen could not be withdrawn in 4. The other two patients left the hospital without need of oxygen after receiving one and six days of treatment with eflornithine and were not considered evaluable for efficacy. The most serious adverse effect was thrombocytopenia, which occurred in 12 of 19 patients treated for ten days or more. Serious bleeding associated with thrombocytopenia was observed in two patients. Other common adverse effects were anorexia, nausea, and diarrhea. Prior to receiving eflornithine, 13 of 15 responders had received ten or more days of conventional therapy without demonstrating clinical improvement. Two had improved while receiving conventional therapy but were switched to eflornithine because of a treatment-limiting adverse effect of standard therapy. These results suggest that eflornithine may be useful as an alternative therapeutic agent for Pneumocystis carinii pneumonia. Studies designed to determine proper dosage, duration of therapy, and efficacy as primary therapy are warranted.

Epidemiological spectrum and current treatment of listeriosis.

To reassess the epidemiology and treatment of listeriosis in the United States, we reviewed greater than 120 cases of listeriosis from four medical centers in three geographically separated cities: Los Angeles County-University of Southern California Medical Center (LAC-USCMC); Rush-Presbyterian-St. Luke's Hospital, Chicago; the University of Illinois Hospital, Chicago; and Vanderbilt University Hospital, Nashville, Tennessee. The epidemiological pattern at LAC-USCMC was relatively narrow; more than two-thirds of the cases occurred during the perinatal period. Cases at Vanderbilt University Hospital represented the opposite end of the spectrum; the majority of these occurred in nonpregnant, older adults who had received organ transplants. An intermediate pattern of cases was observed at the two medical centers in Chicago. Potential risk factors included pregnancy, neonatal status, organ transplantation, renal failure, malignancy, systemic lupus erythematosus, steroid therapy, and AIDS (two cases). Antimicrobial agents noted to be effective were, as expected, penicillin and ampicillin; the cephalosporins were ineffective. The mortality associated with listeriosis occurred mainly among premature infants and stillbirths delivered from infected pregnant women and was markedly less among neonates and adults.

Susceptibility testing of Listeria monocytogenes. A reassessment of bactericidal activity as a predictor for clinical outcome.

In vitro susceptibility testing of Listeria monocytogenes most often reveals both ampicillin and penicillin as inhibitory as opposed to bactericidal with activity comparable to chloramphenicol and tetracycline. Yet, the former two penicillins are more effective for Listeria meningitis than are the latter agents. Accordingly, we reassessed the bactericidal activity of agents used in listeriosis in order to determine in vitro methodology that would be more predictive of clinical outcome. We found that bactericidal activity for greater than 48 hr by either minimum inhibitory-minimum bactericidal concentration (MIC-MBC) testing or time-kill kinetic studies was the best predictor of clinical efficacy. This correlation may be due to Listeria being a slow-growing microorganism. In addition to ampicillin and penicillin, we found trimethoprim-sulfamethoxazole, vancomycin, and imipenem to exhibit bactericidal activity for 48 hr. For the first two agents, this is in agreement with the results of clinical experience.

Epidemiology, antimicrobial susceptibility, pathogenicity, and significance of Bacteroides fragilis group organisms isolated at Los Angeles County-University of Southern California Medical Center.

The epidemiology of species of the Bacteroides fragilis groups isolated at Los Angeles County-University of Southern California Medical Center was examined. In addition, frequency of resistance to six beta-lactam antibiotics (cefmetazole, cefotetan, ceftizoxime, imipenem, penicillin, and cefoxitin) and to clindamycin, chloramphenicol, and metronidazole was determined for each species. While B. fragilis was most commonly isolated, the other species of the B. fragilis group accounted for half of the isolates. Seven percent of 1,128 patients with infections due to species of the B. fragilis group were bacteremic. A review of bacteremic cases indicated that non-fragilis species were highly pathogenic. Resistance to clindamycin ranged from 8% to 22% among species and was most common among isolates of Bacteroides distasonis and Bacteroides thetaiotaomicron. Significant differences in antimicrobial activity were noted among the agents tested. Only imipenem, chloramphenicol, and metronidazole were predictably effective against non-fragilis species of the B. fragilis group. Prompt identification of species and susceptibility testing of clinical isolates of this group are needed if a newer beta-lactam agent or clindamycin is to be used for initial therapy.

Results of extended peptide T administration in AIDS and ARC patients.

We report here the extended Phase I testing of d-ala-Peptide-T-amide (Peptide T) in open trial. The drug was given intravenously in doses ranging from 0.1 to 3.2 mg/kg/day to 14 acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) patients for 12 weeks. Following a 4-week off-drug period, the first 6 patients finishing the intravenous testing were continued on intranasal drug, 25 mg/day, for 8 weeks. Control subjects were tested on the same neuropsychologic tests, but did not receive drug. Minimal evidence of toxicity was found. Performance increments in cognitive and neuromotor function were observed in patients with moderate neuropsychologic impairment compared with controls. Changes in constitutional symptoms included weight gain averaging 2 kg and reported improved sense of well-being. The latter findings were independent of variation in cognitive and neuromotor function. Measures of immunologic function and antiviral activity did not change significantly during the study. These data provide a scientific rationale for Phase II testing of Peptide T in human immunodeficiency virus-1 (HIV-1) patients focusing on neuropsychiatric outcome.

Analysis of cefepime tissue penetration into human appendix.

Cefepime is a new extended-spectrum cephalosporin with gram-positive and gram-negative coverage including Staphylococcus aureus and Pseudomonas aeruginosa. We evaluated the drug's plasma, peritoneal fluid, and appendix tissue concentrations in patients with a postoperative diagnosis of perforated or gangrenous appendicitis. Patients 18 years of age or older were randomly assigned to receive either cefepime 2 g every 12 hours plus metronidazole 500 mg every 6 hours intravenously, or gentamicin 1.5 mg/kg plus clindamycin 900 mg every 8 hours intravenously. During surgery, appendix tissue, plasma, and peritoneal fluid samples were obtained, and frozen at -70 degrees C for high-pressure liquid chromatographic analysis. Thirty-five patients with perforated (26) or gangrenous (9) appendicitis had concentrations acceptable for analysis. The mean time between the administration of cefepime and the time of sampling (referred to as delta time) was 5.99 +/- 3.75 hours (mean +/- SD). The values for plasma (n = 34), tissue (n = 33), and peritoneal fluid (n = 25) concentrations were 16.27 +/- 21.87 micrograms/ml, 4.84 +/- 6.15 micrograms/g, and 14.4 +/- 22.84 micrograms/ml, respectively. The appendix tissue:plasma ratio was 0.66 +/- 0.52 and the peritoneal fluid:plasma ratio was 0.66 +/- 0.51. Spearman rank correlations indicated statistically significant correlations between plasma concentration (r = -0.889; p less than 0.0001), peritoneal fluid concentration (r = -0.783; p = 0.0002), and appendix tissue concentration (r = -0.704; p = 0.0016) versus delta time.(ABSTRACT TRUNCATED AT 250 WORDS)