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D P Levine

Publications and source records attributed to D P Levine.

At least 19 recordsLinked to original sources
PubMed2000

Once-daily aminoglycoside in the treatment of Enterococcus faecalis endocarditis: case report and review.

Once-daily administration of aminoglycosides (ODA) is effective and safe for many indications. By optimizing pharmacodynamic principles, it enhances bactericidal activity and minimizes toxicity. Its use for the treatment of enterococcal infection is controversial, however, and results of in vitro studies and animal models of endocarditis are conflicting. To date, no case reports or clinical trials have examined its utility in human enterococcal endocarditis. A patient with right-sided endocarditis caused by Enterococcus faecalis was managed by once-daily gentamicin. Clinical and bacteriologic cures of this patient raise questions as to whether enterococcal endocarditis should be regarded as contraindication to ODA. The clinical utility of ODA in this disease deserves further investigation.

Adult↗
PubMed1999

Evaluation of Acinetobacter baumannii infection and colonization, and antimicrobial treatment patterns in an urban teaching hospital.

In 1990 there was a sudden increase in the incidence of colonization and infection due to Acinetobacter baumannii (AB) in our intensive care units (ICUs). The isolates were multiply resistant to beta-lactam and aminoglycoside antibiotics, but remained susceptible to imipenem, amikacin, and ampicillin-sulbactam. We examined the frequency of infection and colonization with AB and the effects of increased imipenem and amikacin therapy on Pseudomonas aeruginosa. We also used disease-matched controls to determine the clinical and financial impacts of treating colonization. All patients with at least one AB isolate from January-December 1992 were identified retrospectively and classified as infected or colonized based on published Centers for Disease Control criteria; the control group was selected from a computerized medical records data base matching primary diagnostic codes (102 patients both groups). The 102 patients yielded 140 isolates, 124 resistant AB and 16 sensitive AB. Thirty three patients were infected, 69 colonized. Mortality correlated with APACHE II scores. Patients acquired the organism approximately 2 weeks after admission; they had a mean ICU stay of 27.35 days, compared with 5.53 days for controls. Patients with positive AB cultures required significantly more use of ventilators than those with negative AB cultures. They also had significantly longer hospital stay, more bed transfers, greater duration and number of antibiotics, and higher hospital and pharmacy charges. Unnecessary treatment for colonization with either imipenem or amikacin resulted in a substantial decrease of P. aeruginosa susceptibility to each agent. The financial impact of treating colonization was significant and is a potential area for cost avoidance. Our results emphasize the need to extubate and move patients to non-ICU beds as soon as possible to decrease the risk of nosocomial infection. It also highlights the need to avoid treating colonization, thus avoiding unnecessary antibiotic therapy.

Acinetobacter↗
PubMed1996

Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections.

Ten patients were treated with conventional dosing (CD) and continuous-infusion (CI) vancomycin therapy in this prospective, randomized, crossover study. Patients were randomized to receive either CD or CI therapy for 2 consecutive days and then crossed over to receive the opposite regimen for 2 days. CD therapy consisted of 1 g of vancomycin every 12 h. CI therapy consisted of a 500-mg loading dose followed by 2 g infused over 24 h. Ten serum samples were obtained on the second day of each therapy for pharmacokinetic and pharmacodynamic analyses. Two clinical isolates of Staphylococcus aureus, one methicillin sensitive (MSSA 1199) and one methicillin resistant (MRSA 494), were chosen for pharmacodynamic evaluation of both regimens. The patient demographics (means +/- standard deviations [SD]) were as follows: sex, six males, four females; age, 36 +/- 11 years; and serum creatinine, 0.72 +/- 0.18 mg/dl. Mean pharmacokinetic parameters +/- SD for CD therapy were as follows: elimination rate constant, 0.16 +/- 0.07 h-1; half-life, 5.6 +/- 3.5 h; volume of distribution, 33.7 +/- 25 liters, 0.5 +/- 0.2 liters/kg; maximum concentration in serum, 53.4 +/- 19.3 micrograms/ml; and minimum concentration, 8.4 +/- 5.9 micrograms/ml. The steady-state concentration for CI was 20.2 +/- 11.1 micrograms/ml. Overall, both regimens resulted in the MIC being exceeded 100% of the time. The mean CD trough serum bactericidal titer (SBT) was 1:8, and the average CI SBTs were 1:16 for both isolates. Even though there was no statistically significant difference between CD trough and CI SBTs, the CI SBTs remained > 1:8 for 100% of the time versus 60% of the time for CD therapy. During CI therapy, 20 and 40% of the patients maintained SBTs of > 1:32 throughout the dosing interval for MSSA 1199 and MRSA 494, respectively. During CD therapy, however, only 10% of patients maintained SBTs of > 1:32 during the entire dosing interval for both isolates. The mean areas under the bactericidal titer-time curve (AUBC24s) +/- SD for MSSA 1199 were 528 +/- 263 for CD therapy and 547 +/- 390 for CI therapy. The mean AUBC24s +/- SD against MRSA 494 were 531 +/- 247 for CD and 548 +/- 293 for CI therapy. Similar to the AUBC24, the mean area under the concentration-time curve for a 24-h dosing interval divided by the MIC (AUC/MIC24) ratios +/- SD were 550.0 +/- 265.7 for CD and 552.6 +/- 373.4 for CI therapy, respectively. No statistically significant differences were found between any of the pharmacodynamic parameters for CD and CI therapy. In addition, no adverse effects with either CD or CI therapy were observed during the study. We conclude that CI and CD vancomycin therapy demonstrated equivalent pharmacodynamic activities. Although CI therapy was more likely to result in SBTs that remained above 1:8 for the entire regimen, the clinical impact of this result is unknown. Serum drug concentration variability was observed with both treatment regimens but to a lesser extent with CI administration. CI administration of vancomycin should be further evaluated to determine the clinical utility of this method of administration.

Adult↗
PubMed1992

Delayed detection of an increase in resistant Acinetobacter at a Detroit hospital.

OBJECTIVE: To study an increase of antimicrobial-resistant Acinetobacter baumannii and to assess reasons for the delayed detection of this increase. DESIGN: Review of medical, laboratory, and infection control records. Plasmid profile analysis of available A baumannii isolates. SETTING: A 340-bed trauma and intensive care hospital in Detroit, Michigan. RESULTS: The number of hospitalized patients with resistant A baumannii increased during late 1989 and early 1990: 4 in September, 10 in October, 12 in November, 18 in December, and 23 in January (chi square for trend = 14.6, p = .0001). Forty-four (66%) of the 67 patients culture-positive for resistant A baumannii had respiratory tract colonization or infection. Of 11 resistant isolates, 6 had a similar plasmid profile and 5 had no plasmids. Under the hospital's targeted surveillance system, only positive cultures from blood or wounds were investigated; this largely respiratory increase of resistant A baumannii went unrecognized until January 1990. CONCLUSIONS: Antimicrobial resistance in A baumannii is an important concern. Such resistance is not necessarily plasmid mediated. Targeted surveillance for this and other agents of nosocomial infection should be used with caution, particularly in hospitals with many debilitated patients.

Acinetobacter↗
PubMed1992

Nephrotoxicity and ototoxicity of aztreonam versus aminoglycoside therapy in seriously ill nonneutropenic patients.

A randomized double-blind clinical trial was done of aztreonam versus aminoglycoside therapy for the empiric treatment of seriously ill nonneutropenic patients suspected of aerobic gram-negative bacterial infection. Each patient was treated for greater than or equal to 72 h with the study drug. Nephrotoxicity, defined by greater than or equal to 50% increase in baseline serum creatinine, occurred in 12 (15%) of 92 patients receiving aminoglycoside therapy and 1 (1%) of 92 patients receiving aztreonam (P less than .004). More severe nephrotoxicity, defined by greater than or equal to 100% increase in baseline serum creatinine, occurred in 6 (6.5%) of 92 patients receiving aminoglycoside therapy and in 1 of 92 receiving aztreonam (P less than .11). Patients with an elevated baseline total bilirubin level were most likely to develop nephrotoxicity. Auditory toxicity occurred in 2 (7%) of 28 evaluatable patients receiving aminoglycoside therapy and in 1 (3%) of 33 receiving aztreonam (P less than .58). One patient, who received aminoglycoside, developed vestibular toxicity. In nonneutropenic patients believed to be at increased risk for renal dysfunction, aztreonam is a less toxic alternative to aminoglycoside therapy for treatment of suspected aerobic gram-negative infection.

Aminoglycosides↗
PubMed1991

Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis.

OBJECTIVE: To determine the median response time to therapy with vancomycin alone or with vancomycin plus rifampin in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. DESIGN: Cohort analysis of a randomized study. SETTING: University medical center. PATIENTS: Forty-two consecutive patients with MRSA endocarditis were randomly assigned to receive either vancomycin (group I) or vancomycin plus rifampin (group II) for 28 days. MEASUREMENTS: Clinical signs and symptoms were recorded, and blood cultures were obtained daily to determine the duration of bacteremia. MAIN RESULTS: The median duration of bacteremia was 9 days (7 days for group I and 9 days for group II). The median duration of fever for all patients and for each treatment group was 7 days. Six patients failed therapy, including three patients who died 5, 6, and 9 days after therapy was started, respectively. The other three patients who failed therapy required valve surgery on days 2, 22, and 27, respectively. Although patients had sustained bacteremia, no unusual complications were seen in either treatment group, and most patients responded to continued antibiotic therapy. CONCLUSIONS: Slow clinical response is common among patients with MRSA endocarditis who are treated with vancomycin or vancomycin plus rifampin. Nevertheless, few complications appear to be related solely to this sustained bacteremia.

Adult↗
PubMed1991

Teicoplanin pharmacokinetics in intravenous drug abusers being treated for bacterial endocarditis.

The pharmacokinetics of teicoplanin were determined after multiple 30-min intravenous infusions of 10 to 15 mg/kg every 12 to 24 h in 11 intravenous drug abuse (IVDA) patients being treated for bacterial endocarditis. Multiple serum samples were obtained over 7 to 14 days. Twenty-four-hour urine collections were obtained on days 1 and 5. Serum concentration-time data were analyzed by using multiple-dose pharmacokinetic analysis (NONLIN84). Results were compared with pharmacokinetic parameters derived from previous studies in normal healthy volunteers following multiple intravenous infusions of teicoplanin (3 to 6 mg/kg/day). Total and renal clearances of teicoplanin in IVDA patients were found to be significantly greater and more highly variable than those observed previously in normal healthy volunteers. As a result, predicted steady-state trough concentrations in serum may vary up to fivefold. The mechanism responsible for this variation appears to be related to the glomerular filtration rate. In IVDA patients, individualized teicoplanin dosage may be required in the treatment of bacterial endocarditis.

Adult↗
PubMed1989

Randomized, double-blind comparative study of intravenous ciprofloxacin versus ceftazidime in the treatment of serious infections.

We compared intravenously administered ciprofloxacin with ceftazidime in a randomized, double-blind study. Patients received ciprofloxacin 200 mg intravenously every 12 hours or ceftazidime 2 g intravenously every eight hours, with placebo infusions to maintain blinding. Therapy with metronidazole was added for suspected or documented intra-abdominal infection. Thirty-two of the 57 ciprofloxacin-treated patients were evaluable for determination of efficacy and had 41 bacterial isolates from 34 sites. Thirty-six of the 56 ceftazidime patients were evaluable for determination of efficacy and had 41 bacterial isolates from 38 sites. Seven of 35 bacteremic patients had no identifiable primary focus. The most commonly isolated pathogens were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae. Cure rates and bacteriologic eradication rates were comparable. Nine patients did not improve. Patients with treatment failures in the ciprofloxacin group included a quadriplegic patient with relapse of urinary tract infection with bacteremia (K. pneumoniae). Another patient with bacteremia (Pseudomonas aeruginosa), pneumonia (Proteus vulgaris), and urinary tract infection (P. vulgaris, Providencia sp.) died on the first treatment day. The third patient (S. aureus and Streptococcus pneumoniae pneumonia) had a new aspiration pneumonia develop on the third day; the pneumococcus also persisted. Undrained S. pneumoniae empyema caused the fourth ciprofloxacin treatment failure, and the fifth patient had a relapse of S. aureus pneumonia with bacteremia. One ceftazidime-treated patient died of pneumococcal pneumonia on the first day. Another had persistent Staphylococcus epidermidis and Listeria bacteremia despite 48 hours of treatment. Two other patients had pneumonia (S. aureus and P. aeruginosa, respectively) and completed full courses of ceftazidime therapy without improvement. Five patients had pneumococcal bacteremia; four patients were cured: one of two patients in the ciprofloxacin group and three of three patients in the ceftazidime group. Significant increases in the number of platelets (four patients with ciprofloxacin treatment, one patient with ceftazidime treatment) and declines in the number of platelets (one patient with ciprofloxacin treatment, one patient with ceftazidime treatment) were observed. Intravenously administered ciprofloxacin is comparable with ceftazidime and is a safe and effective antibiotic for the treatment of patients with serious infections, including bacteremia.

Bacterial Infections↗
PubMed1988

Comparative efficacies of imipenem-cilastatin and vancomycin in experimental aortic valve endocarditis due to methicillin resistant Staphylococcus aureus.

Activities of imipenem and vancomycin against methicillin resistant Staphylococcus aureus (MRSA) were compared in vitro and in a rabbit model of aortic valve endocarditis. Against 25 MRSA clinical isolates, imipenem was bacteriostatic (MIC90/MBC90, mg/l 8/32) in vitro while vancomycin was bactericidal (MIC90/MBC90, mg/l 2/4). Rabbit endocarditis was produced with a MRSA isolate against which both drugs were bactericidal. Imipenem-cilastatin had better efficacy than vancomycin by the following criteria, the number of survivors (9/13 vs 7/13), clearance of bacteraemia (9/9 vs 3/7; P = 0.019), sterility of cardiac vegetations (9/9 vs 1/7; P = 0.001) and sterility of distant organs (8/9 vs 2/7; P = 0.035). Thus, imipenem-cilastatin may be a potentially useful alternative agent to vancomycin in the therapy of MRSA endocarditis in the occasional situations when the drug demonstrates in-vitro bactericidal activity against the pathogen. Efficacy against MRSA strains with higher MBCs remains to be proved.

Animals↗
PubMed1988

Treatment of penetrating abdominal trauma and gynecologic infections.

Both penetrating abdominal trauma and gynecologic infections are polymicrobial and require antibiotics with broad-spectrum activity against both aerobic and anaerobic pathogens. In an open study, ticarcillin disodium/clavulanate potassium was used to treat patients with penetrating abdominal trauma, intraabdominal infection or gynecologic infection. Ticarcillin disodium/clavulanate potassium was administered at a dose of 3.1 g every four or every six hours, and therapy lasted for a minimum of three days. Among 20 patients with intraabdominal infections that involved abdominal organ perforation, ticarcillin disodium/clavulanate potassium was effective in 16. Eighteen of 19 aerobic isolates were susceptible to ticarcillin disodium/clavulanate potassium, as were all of 21 anaerobic isolates. Fifteen of 21 evaluable patients with gynecologic infections were cured. Among the infections were pelvic inflammatory disease, salpingitis, salpingitis with tuboovarian abscess, pelvic inflammatory disease with tuboovarian abscess, salpingitis/pelvic inflammatory disease and peritonitis, endomyometritis, cervicitis and pelvic inflammatory disease with peritonitis. A total of 32 aerobic and 15 anaerobic organisms were isolated, and 14 of the patients had more than one organism isolated.

Abdominal Injuries↗
PubMed1986

Clinical use and toxicity of high-dose tobramycin in patients with pseudomonal endocarditis.

The effects and toxicity of tobramycin were assessed in 26 patients receiving high-dose (approximately 8 mg/kg/d) therapy for pseudomonal endocarditis or conventional-dose (approximately 3 mg/kg/d) therapy for various systemic Gram-negative infections. Patients in the high-dose group received an average of 29.5 g of drug over 49 days and the dosage was adjusted to maintain peak serum concentrations of 15-20 mg/l. In the conventional-dose group, patients received an average of 8.6 g of tobramycin over 26.7 days and the dosage was adjusted to achieve peak concentrations of 4-10 mg/l. Clinical evidence of acute renal failure was not apparent in any patient. Five of seven patients in the high-dose group, for whom audiologic data was available, exhibited loss of hearing sensitivity in the high frequency range, but no patients sustained significant reduction in hearing in the conversational frequency range. Patients receiving high-dose tobramycin do not appear to be at greater risk for development of nephrotoxicity than do patients receiving conventional-dose therapy.

Adult↗
PubMed1986

In vitro and in vivo activity of coumermycin and other antibacterial agents against methicillin-resistant strains of Staphylococcus aureus.

The in vitro activity of coumermycin, fusidic acid, cotrimoxazole, and vancomycin was determined by broth microdilution assay against 33 methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates from the Detroit Receiving Hospital, Detroit, Mich. Coumermycin was the most active drug tested, while fusidic acid, vancomycin, and cotrimoxazole also had good activity. The four antimicrobials were tested in vivo against 7 strains of MRSA employing the mouse protection model. Again, coumermycin was the most active, followed by vancomycin, cotrimoxazole, and fusidic acid. Coumermycin was very active, while vancomycin and fusidic acid were inactive in neutropenic mice infected with an MRSA strain. Coumermycin retained activity when given 18 h before an MRSA infection, while vancomycin activity was lost. Coumermycin was active in a local thigh infection while vancomycin was inactive. The results indicate that coumermycin is potent against MRSA with activity equal or superior to comparable agents in various experimental mouse infections.

Aminocoumarins↗
PubMed1985

In-vitro evaluation of cefpirome (HR 810), teicoplanin and four other antimicrobials against enterococci.

In-vitro activities of cefpirome (HR 810), a fourth generation cephalosporin, and teicoplanin were compared with those of ampicillin, piperacillin, and vancomycin against 56 clinical isolates of enterococci. Cefpirome had good activity with the MIC90 and MBC90 being 4 and 16 mg/l. Ampicillin and piperacillin had MBC90 of 4 and 16 mg/l. Teicoplanin was extremely active with the MIC90 being 1.6 mg/l while vancomycin had poor cidal activity with the MBC90 being 16 mg/l. A decrease in activity of cefpirome was noted when the inoculum size was increased from 10(3) to 10(7) organisms per ml. Synergy was demonstrated against most Streptococcus faecium isolates with a combination of cefpirome and gentamicin or piperacillin. Against Str. faecalis, with a similar combination, synergy was seen in less than 50% isolates. No antagonism was noted with any of the antibiotic combinations.

Ampicillin↗