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Papers by George Talbot
Antimicrobial Agents and Chemotherapy, 2008
Southern Medical Journal, 2003
A 56-year-old man with diabetes mellitus and cadaveric renal transplantation had vancomycin-resis... more A 56-year-old man with diabetes mellitus and cadaveric renal transplantation had vancomycin-resistant Enterococcus faecium tricuspid valve endocarditis. Relapse followed 6 weeks of treatment with intravenous gentamicin and high-dose ampicillin. On the basis of previous data suggesting the potential for synergistic activity of quinupristin/dalfopristin plus high-dose ampicillin, therapy with this combination was administered for 63 days. Cure was achieved and later confirmed at 2-year follow-up.
Diagnostic Microbiology and Infectious Disease, 1996
Sparfoxacin is a piperazinyl, cyclopropyl-fluoroquinolone zvitk broad-spectrum antibacterial acti... more Sparfoxacin is a piperazinyl, cyclopropyl-fluoroquinolone zvitk broad-spectrum antibacterial activity. Compared to otker quinolones, sparfloxacin displays improved activity against a uariety of pathogens including Staphylococcus, Pseudomonas aeruginosa are not. Sparfloxacin is bactericidal. Activity is generally stable to variations of inoculum, pH, and cation concentration, and it is unchanged in the presence of5% sodium ckolafe or 70% human serum. Susceptibility to tke drug is diminished in urine. Cross-resistance, although incomplete, has been documented with other quinolones, but nof with other antimicrobic classes.
Clinical Therapeutics, 1999
Community-acquired pneumonia remains a significant health concern despite the availability of eff... more Community-acquired pneumonia remains a significant health concern despite the availability of effective antibiotics. This randomized, double-masked, double-dummy, multicenter comparative trial was undertaken to compare the efficacy and safety of sparfloxacin with those of clarithromycin in the treatment of community-acquired pneumonia. In 54 centers throughout the United States, 342 patients aged > or = 18 years with community-acquired pneumonia were enrolled in this trial. A total of 167 patients, 98 males and 69 females with a mean age of 51.0 years (range, 18-87), received a 400-mg loading dose of sparfloxacin on the first day, followed by 200 mg once daily for a total of 10 days. A total of 175 patients, 85 males and 90 females with a mean age of 51.3 years (range, 18-91), received clarithromycin 250 mg twice daily for 10 days. In the intent-to-treat population, 133 (79.6%) patients in the sparfloxacin group and 145 (82.9%) in the clarithromycin group were cured or improved (the 95% confidence interval [CI] for the differences in success rate between sparfloxacin and clarithromycin was -11.5% to 5.1%). Success rates for the per-protocol patients were 88.7% (133/150) in the sparfloxacin group and 88.9% (144/162) in the clarithromycin groups (95% CI, -7.2% to 6.8%). There were no significant differences in success rate between treatment groups based on age > or = 65 years. The overall bacteriologic response rates in the bacteriologically assessable population were 97.0% (64/66 isolates) in the sparfloxacin group and 91.4% (74/81 isolates) in the clarithromycin group. Recurrence occurred in 6.0% of per-protocol patients in the sparfloxacin group and 6.3% of patients in the clarithromycin group. The overall frequency of adverse events was 56.3% in the sparfloxacin group and 65.1% in the clarithromycin group. Gastrointestinal disturbances were the most common adverse event in both groups. Abnormal taste related to study drug was reported by 17 patients (9.7%) treated with clarithromycin, versus 3 patients (1.8%) treated with sparfloxacin (P = 0.002). Photosensitivity reactions were reported in 10 patients (6.0%) treated with sparfloxacin, versus 1 patient (0.6%) treated with clarithromycin (P = 0.002). QT-interval prolongation was documented in 4 patients (2.4%) in the sparfloxacin group and no patients in the clarithromycin group. Thus sparfloxacin was as well tolerated and as effective as clarithromycin in the treatment of community-acquired pneumonia.
Antimicrobial Agents and Chemotherapy, 2007
American Journal of Medicine, 1998
This report summarizes the activities of quinupristin/ dalfopristin (Q/D) and appropriate compara... more This report summarizes the activities of quinupristin/ dalfopristin (Q/D) and appropriate comparator antibiotics, including ciprofloxacin, erythromycin, gentamicin, rifampin, teicoplanin, and vancomycin, against selected gram-positive pathogens, including Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus agalactiae, and Streptococcus pyogenes. The study pathogens were obtained from 2 sources: (1) clinical isolates taken from patients participating in Q/D worldwide Phase III comparative and noncomparative (emergency-use program) clinical trials; and (2) other isolates collected from the laboratories of 45 geographically distinct medical centers around the world. Q/D was highly active, with minimum inhibitory concentrations (MICs) ≤1.0 g/mL against most isolates, including those known to be resistant to methicillin, vancomycin, or erythromycin. Q/D was active (MICs ≤1 g/mL) against 95% of the vancomycin-resistant E. faecium strains, for example, whereas ciprofloxacin was active against 6%. Q/D was equally active against methicillin-susceptible or -resistant S. aureus strains (MIC 90 ؍ 1 g/mL), as was vancomycin (MIC 90 ؍ 2 g/mL), whereas ciprofloxacin was much less active against methicillin-resistant strains than against methicillin-susceptible strains (MIC 90 ؍ 32 vs 1 g/mL). Given its spectrum of activity, Q/D may provide a viable option for the treatment of severe respiratory and skin and skin-structure infections caused by gram-positive bacteria, especially when strains with known or suspected resistance to other commonly used antibiotics are present. Am J Med. 1998;104(5A): 34S-42S.
Clinical Infectious Diseases, 2006
The Antimicrobial Availability Task Force (AATF) of the Infectious Diseases Society of America (I... more The Antimicrobial Availability Task Force (AATF) of the Infectious Diseases Society of America (IDSA) has viewed with concern the decreasing investment by major pharmaceutical companies in antimicrobial research and development. Although smaller companies are stepping forward to address this gap, their success is uncertain. The IDSA proposed legislative and other federal solutions to this emerging public health problem in its July 2004 policy report "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews." At this time, the legislative response cannot be predicted. To emphasize further the urgency of the problem for the benefit of legislators and policy makers and to capture the ongoing frustration our clinician colleagues experience in their frequent return to an inadequate medicine cabinet, the AATF has prepared this review to highlight pathogens that are frequently resistant to licensed antimicrobials and for which few, if any, potentially effective drugs are identifiable in the late-stage development pipeline.
American Journal of Medicine, 1989
A case-control study was performed to identify and quantify risk factors for amphotericin B-assoc... more A case-control study was performed to identify and quantify risk factors for amphotericin B-associated nephrotoxicity. Thirty-five patients receiving intravenous amphotericin B for treatment of proven or suspected fungal infection who developed nephrotoxicity (greater than 100% increase in baseline serum creatinine to a level above the normal range) were compared with 60 control patients receiving amphotericin B who did not develop nephrotoxicity. Amphotericin B dosing variables and other potential risk factors were analyzed in a logistic regression model. Cases of nephrotoxicity received a significantly higher average daily dose of amphotericin B (0.49 +/- 0.18 mg/kg/day) than did controls (0.34 +/- 0.17 mg/kg/day). In a multivariate model, the risk of nephrotoxicity increased 3.7-fold for each 50-mg increase in total dose for a fixed duration of therapy and patient weight. Risk decreased by a factor of 0.4 for each extra day of therapy for a fixed total dose and weight. An increase in weight was also protective when the two other dosage variables were held constant. Each 0.10 mg/kg/day dose increment was associated with a 1.8-fold (95% confidence interval, 1.2 to 2.7) increase in the risk of nephrotoxicity. Other significant risk factors included diuretic use during amphotericin B therapy (12.5, 1.7 to 94.7), for which a linear dose-response relationship was demonstrated, and an abnormal baseline serum creatinine level (15.4, 1.4 to 173.2). Risk factors for amphotericin B-associated nephrotoxicity include higher average daily doses (approximately a doubling for each 0.10 mg/kg/day increment), diuretic use, and abnormal baseline renal function. These data suggest possible protective interventions and will aid clinicians in assessing the risk-benefit ratio of amphotericin B therapy for deep fungal infection.
American Journal of Medicine, 1989
The purpose of this study was to define risk factors for nosocomial candidemia in adult patients ... more The purpose of this study was to define risk factors for nosocomial candidemia in adult patients without leukemia at a tertiary care medical center. All patients with nosocomial candidemia between August 1, 1981, and October 31, 1984, were included if they met strict selection criteria and did not have acute or chronic leukemia. For each case, one control was selected from among patients admitted during the same month/year and matched for hospital service and duration of hospitalization up to the first blood culture that grew Candida species. Logistic regression was used to obtain estimates of risk after simultaneously controlling for other variables. Candida albicans caused 24 of the 48 fungemias studied. The risk factors identified included the presence of a central line (odds ratio, 26.4; 95% confidence interval, 1.5 to 451.1); bladder catheter (13.0 1.3 to 131.4); two or more antibiotics (25.1, 2.1 to 318); azotemia (22.1, 2.2 to 223.2); transfer from another hospital (21.3, 1.7 to 274.5); diarrhea (10.2, 1.03 to 101.4); and candiduria (27.0, 1.7 to 423.5). A prior surgical procedure was associated with lowered risk (0.1, 0.01 to 0.9), suggesting perhaps that medical service patients are at higher risk than those on surgical services. Because total parenteral nutrition was always administered by means of a central line, it could not be shown to increase the risk over that conferred by a central line alone. This study has defined seven major risk factors for nosocomial candidemia. These findings should facilitate development of rational approaches to preventing infection and may assist clinicians in identifying those patients in whom this life-threatening complication is likely to occur.
American Journal of Medicine, 1985
Dental Traumatology, 1988
Abstract Survival of bacteria in periapical tissues may be the reason for endodontic failures. Th... more Abstract Survival of bacteria in periapical tissues may be the reason for endodontic failures. This case report describes the treatment of a patient with periapical lesions refractory to endodontic treatment. Microbiological sampling from fistulae associated with the lesions revealed the presence of Pseudomonas aeruginosa. Phenoxymethyl penicillin, metronidazole and carbenicillin were ineffective in eliminating the periapical infection. However, an investigational antibiotic, Ciprofloxacin, which was administered orally twice daily for 15 weeks, proved to be an effective, safe and convenient medicament in the treatment of periapical Pseudomonas aeruginosa infection. The fistulae closed in less than 2 weeks and a radiograph taken during the fourteenth week of therapy showed healing of the apical periodontitis with osseous regeneration. It is suggested that Ciprofloxacin is a valuable agent in the treatment of apical periodontitis, and probably other odontogenic infections caused by susceptible aerobic gram-negative bacilli.
Infection Control and Hospital Epidemiology, 1990
The hospital-wide attack rate for Clostridium difficile-associated diarrhea at our tertiary-care ... more The hospital-wide attack rate for Clostridium difficile-associated diarrhea at our tertiary-care university hospital was 0.02 per 100 patient discharges (0.02%) in 1982, but 0.41% and 1.47% in 1986 and 1987, respectively, with a peak incidence of 2.25% in the fourth quarter of 1987. Hospital antibiotic usage patterns showed concurrent increased use of third-generation cephalosporins, and intravenous vancomycin and metronidazole. Thirty-seven cases selected for study were older than 37 control patients, more likely to have an underlying malignancy and less likely hospitalized on the obstetrics/gynecology service. Their mean duration of hospitalization prior to diagnosis was 21 days, versus a mean total length of stay of eight days for controls. All cases received antibiotics, compared to 24 of the controls. Cases were given more antibiotics for longer periods, and more often received clindamycin, third-generation cephalosporins, aminoglycosides and vancomycin. Gender, race, duration of hospitalization, prior surgery and antiulcer therapy were not significant by logistic regression analysis. Epidemiologic variables with significantly different adjusted odds ratios (95% confidence intervals) were age greater than 65 years (14.1, 1.4-141), intensive care unit residence (39.2, 2.2-713), gastrointestinal procedure (23.2, 2.1-255) and more than ten antibiotic days (summation of days of each antibiotic administered) (16.1, 2.2-117). Control measures included encouraging earlier isolation and treatment of suspected cases and formulary restriction of clindamycin, with use of metronidazole for therapy of anaerobic infections. By the second half of 1988, the attack rate had dropped progressively to 0.74%.
Infection Control and Hospital Epidemiology, 1988
An epidemic of adenovirus 7a in our neonatal intensive care nursery and intermediate care nursery... more An epidemic of adenovirus 7a in our neonatal intensive care nursery and intermediate care nursery in July and August 1987 caused the death of two patients. Significant symptomatic infection possibly due to the virus occurred in nine patients, ten staff, and three parents, of whom three patients, three staff, and one parent were positive by culture. As a direct consequence of the outbreak, 58 staff days of work were lost; the intensive care nursery had to be closed to admissions for 19 days and the intermediate care nursery for 14 days. Seventeen newborns were transferred to other hospitals and four mothers were sent elsewhere for delivery. Control measures, which included cohorting of patients, use of gloves, gowns and goggles, and exclusion of symptomatic staff from the unit, appeared effective. Rapid immunofluorescence testing of virological specimens was of little use in monitoring the outbreak, largely because of poor specimen quality. This outbreak further underlines the ease of transmission and high morbidity of neonatal adenovirus infection.
American Journal of Medicine, 1984
The utility and safety of fiberoptic bronchoscopy in the diagnosis of invasive pulmonary aspergil... more The utility and safety of fiberoptic bronchoscopy in the diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia have not been examined. The results of 21 bronchoscopic procedures in 19 patients with invasive pulmonary aspergillosis and acute leukemia were reviewed. Analysis was confined to the 16 patients who had histopathologically documented infection on biopsy or at autopsy. Fiberoptic bronchoscopy established or suggested the diagnosis of invasive pulmonary aspergillosis in eight of 16 (50 percent) patients. Transbronchial or bronchial biopsy added only one diagnosis to those obtained by bronchial washing and brushing. Although fiberoptic bronchoscopy was a safe and well-tolerated procedure in our patients with invasive pulmonary aspergillosis and acute leukemia, its success rate was only 50 percent overall, and it appeared to be even less successful when performed early in the course of the disease. Fiberoptic bronchoscopy is a useful first procedure for the evaluation of patients with acute leukemia and possible invasive pulmonary aspergillosis, but a negative result does not exclude aspergillosis. Further diagnostic procedures, including repeated bronchoscopy, or institution of empiric antifungal therapy may be warranted if the clinical suspicion of invasive pulmonary aspergillosis is high.
Pediatric Infectious Disease Journal, 1988
Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Th... more Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for The Pediatric Infectious Disease Journal. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and ...
Infection Control and Hospital Epidemiology, 1989
We reviewed 402 hospital admissions of patients with acute leukemia to define the frequency and c... more We reviewed 402 hospital admissions of patients with acute leukemia to define the frequency and characteristics of anaerobic bacteremia in this patient population. Six (5.2%) of the 116 septicemia episodes documented in these patients were caused by anaerobes (Bacteroides species, 3; Fusobacterium species, 2; and Clostridium tertium, 1); two of these episodes were polymicrobial. Five patients had had prior bacteremia. All six patients were receiving broad-spectrum antibiotics, including an anti-pseudomonal penicillin, at the time of the episode. In each instance, the absolute granulocyte count was 0/mm3. Five patients had clinically apparent sources of infection, including perirectal abscess, gastrointestinal bleeding, or Clostridium difficile-associated diarrhea. Anaerobic bacteremia is an infrequent occurrence in granulocytopenic patients with acute leukemia, but may occur when there is obvious disruption of normal gastrointestinal anatomic barriers.
Pediatric Infectious Disease Journal, 1988
Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Th... more Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for The Pediatric Infectious Disease Journal. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and ...
Clinical Therapeutics, 1997
Community-acquired pneumonia remains an important infectious disease problem, with more than 4 mi... more Community-acquired pneumonia remains an important infectious disease problem, with more than 4 million cases occurring in the United States annually. Although Streptococcus pneumoniae remains the most commonly identified organism, a variety of bacterial and nonbacterial pathogens may be involved. Hospitalization is unnecessary in most cases, and oral antibiotic therapy is common. In the majority of cases, the etiology of pneumonia is unknown at the time of presentation, necessitating the use of empiric therapy. Quinolones have not been utilized in this setting in the past because of their inconsistent coverage of S pneumoniae. Sparfloxacin (RP 64206) is a broad-spectrum fluoroquinolone with excellent activity in vitro against the majority of bacteria involved in community-acquired pneumonia, including pneumococcus. We therefore studied the efficacy and safety of sparfloxacin compared with the second-generation cephalosporin cefaclor as empiric therapy for patients with community-acquired pneumonia in a double-masked, double-dummy, multicenter trial. Three hundred thirty patients aged 18 years or older with community-acquired pneumonia suspected of being bacterial in etiology were enrolled at 74 centers in the United States from June 1, 1992, to March 4, 1995. Patients meeting the inclusion criteria were randomized to receive 10 days of either sparfloxacin 400 mg orally once followed by sparfloxacin 200 mg orally daily (n = 168), or cefaclor 500 mg orally every 8 hours (n = 162). There were no significant differences between groups with regard to baseline characteristics. Patients were followed up serially at 4 +/- 1 days, 20 +/- 3 days, and 38 +/- 7 days after the beginning of therapy. Patients were evaluated for clinical response, clinical recurrence of infection, and eradication of baseline pathogens. The primary efficacy variable was the clinical response (cured or improved) in the subgroup of patients meeting the definition of clinically assessable. Responses were also evaluated in the intent-to-treat population. In the intent-to-treat population, 35.7% of patients receiving sparfloxacin were clinically cured, compared with 32.1% of patients receiving cefaclor. Clinical successes (patients clinically cured plus improved) were also comparable (72.6% of patients in the sparfloxacin group and 71.0% of patients in the cefaclor group). Similar clinical success rates were noted using only the clinically assessable population (primary efficacy variable). Forty-four percent of patients receiving sparfloxacin and 39.1% of patients receiving cefaclor were clinically cured. In the sparfloxacin group, 86.6% of patients were clinical successes, compared with 84.4% of patients in the cefaclor group. Microbiologic cures were comparable in both groups. There was no difference in the incidence of recurrence of infection or superinfection. Adverse events thought to be due to study drug occurred equally in both groups (14.3% in the sparfloxacin group vs 14.8% in the cefaclor group). Results show that sparfloxacin is a safe and effective empiric therapy for patients with community-acquired pneumonia and is comparable to cefaclor.
Expert Review of Anti-infective Therapy, 2008
The emergence of new human pathogens and increasing antimicrobial resistance in well-established ... more The emergence of new human pathogens and increasing antimicrobial resistance in well-established pathogens are critical public health concerns. Unfortunately, the pipeline of new antimicrobial candidates remains remarkably lean for molecules active against increasingly problematic Gram-negative bacterial pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa. Although a number of new anti-Gram-negative antibacterial agents are likely to be introduced soon for clinical use, they will not represent a quantum leap in our ability to effectively treat these human pathogens of great concern. New classes of antimicrobials with novel mechanisms of action and new approaches to increasing the effectiveness of traditional antimicrobials are urgently needed. Renewed research and development efforts must become a priority, lest we fall further behind in our therapeutic initiatives.
Antimicrobial Agents and Chemotherapy, 2008
Southern Medical Journal, 2003
A 56-year-old man with diabetes mellitus and cadaveric renal transplantation had vancomycin-resis... more A 56-year-old man with diabetes mellitus and cadaveric renal transplantation had vancomycin-resistant Enterococcus faecium tricuspid valve endocarditis. Relapse followed 6 weeks of treatment with intravenous gentamicin and high-dose ampicillin. On the basis of previous data suggesting the potential for synergistic activity of quinupristin/dalfopristin plus high-dose ampicillin, therapy with this combination was administered for 63 days. Cure was achieved and later confirmed at 2-year follow-up.
Diagnostic Microbiology and Infectious Disease, 1996
Sparfoxacin is a piperazinyl, cyclopropyl-fluoroquinolone zvitk broad-spectrum antibacterial acti... more Sparfoxacin is a piperazinyl, cyclopropyl-fluoroquinolone zvitk broad-spectrum antibacterial activity. Compared to otker quinolones, sparfloxacin displays improved activity against a uariety of pathogens including Staphylococcus, Pseudomonas aeruginosa are not. Sparfloxacin is bactericidal. Activity is generally stable to variations of inoculum, pH, and cation concentration, and it is unchanged in the presence of5% sodium ckolafe or 70% human serum. Susceptibility to tke drug is diminished in urine. Cross-resistance, although incomplete, has been documented with other quinolones, but nof with other antimicrobic classes.
Clinical Therapeutics, 1999
Community-acquired pneumonia remains a significant health concern despite the availability of eff... more Community-acquired pneumonia remains a significant health concern despite the availability of effective antibiotics. This randomized, double-masked, double-dummy, multicenter comparative trial was undertaken to compare the efficacy and safety of sparfloxacin with those of clarithromycin in the treatment of community-acquired pneumonia. In 54 centers throughout the United States, 342 patients aged > or = 18 years with community-acquired pneumonia were enrolled in this trial. A total of 167 patients, 98 males and 69 females with a mean age of 51.0 years (range, 18-87), received a 400-mg loading dose of sparfloxacin on the first day, followed by 200 mg once daily for a total of 10 days. A total of 175 patients, 85 males and 90 females with a mean age of 51.3 years (range, 18-91), received clarithromycin 250 mg twice daily for 10 days. In the intent-to-treat population, 133 (79.6%) patients in the sparfloxacin group and 145 (82.9%) in the clarithromycin group were cured or improved (the 95% confidence interval [CI] for the differences in success rate between sparfloxacin and clarithromycin was -11.5% to 5.1%). Success rates for the per-protocol patients were 88.7% (133/150) in the sparfloxacin group and 88.9% (144/162) in the clarithromycin groups (95% CI, -7.2% to 6.8%). There were no significant differences in success rate between treatment groups based on age > or = 65 years. The overall bacteriologic response rates in the bacteriologically assessable population were 97.0% (64/66 isolates) in the sparfloxacin group and 91.4% (74/81 isolates) in the clarithromycin group. Recurrence occurred in 6.0% of per-protocol patients in the sparfloxacin group and 6.3% of patients in the clarithromycin group. The overall frequency of adverse events was 56.3% in the sparfloxacin group and 65.1% in the clarithromycin group. Gastrointestinal disturbances were the most common adverse event in both groups. Abnormal taste related to study drug was reported by 17 patients (9.7%) treated with clarithromycin, versus 3 patients (1.8%) treated with sparfloxacin (P = 0.002). Photosensitivity reactions were reported in 10 patients (6.0%) treated with sparfloxacin, versus 1 patient (0.6%) treated with clarithromycin (P = 0.002). QT-interval prolongation was documented in 4 patients (2.4%) in the sparfloxacin group and no patients in the clarithromycin group. Thus sparfloxacin was as well tolerated and as effective as clarithromycin in the treatment of community-acquired pneumonia.
Antimicrobial Agents and Chemotherapy, 2007
American Journal of Medicine, 1998
This report summarizes the activities of quinupristin/ dalfopristin (Q/D) and appropriate compara... more This report summarizes the activities of quinupristin/ dalfopristin (Q/D) and appropriate comparator antibiotics, including ciprofloxacin, erythromycin, gentamicin, rifampin, teicoplanin, and vancomycin, against selected gram-positive pathogens, including Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus agalactiae, and Streptococcus pyogenes. The study pathogens were obtained from 2 sources: (1) clinical isolates taken from patients participating in Q/D worldwide Phase III comparative and noncomparative (emergency-use program) clinical trials; and (2) other isolates collected from the laboratories of 45 geographically distinct medical centers around the world. Q/D was highly active, with minimum inhibitory concentrations (MICs) ≤1.0 g/mL against most isolates, including those known to be resistant to methicillin, vancomycin, or erythromycin. Q/D was active (MICs ≤1 g/mL) against 95% of the vancomycin-resistant E. faecium strains, for example, whereas ciprofloxacin was active against 6%. Q/D was equally active against methicillin-susceptible or -resistant S. aureus strains (MIC 90 ؍ 1 g/mL), as was vancomycin (MIC 90 ؍ 2 g/mL), whereas ciprofloxacin was much less active against methicillin-resistant strains than against methicillin-susceptible strains (MIC 90 ؍ 32 vs 1 g/mL). Given its spectrum of activity, Q/D may provide a viable option for the treatment of severe respiratory and skin and skin-structure infections caused by gram-positive bacteria, especially when strains with known or suspected resistance to other commonly used antibiotics are present. Am J Med. 1998;104(5A): 34S-42S.
Clinical Infectious Diseases, 2006
The Antimicrobial Availability Task Force (AATF) of the Infectious Diseases Society of America (I... more The Antimicrobial Availability Task Force (AATF) of the Infectious Diseases Society of America (IDSA) has viewed with concern the decreasing investment by major pharmaceutical companies in antimicrobial research and development. Although smaller companies are stepping forward to address this gap, their success is uncertain. The IDSA proposed legislative and other federal solutions to this emerging public health problem in its July 2004 policy report "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews." At this time, the legislative response cannot be predicted. To emphasize further the urgency of the problem for the benefit of legislators and policy makers and to capture the ongoing frustration our clinician colleagues experience in their frequent return to an inadequate medicine cabinet, the AATF has prepared this review to highlight pathogens that are frequently resistant to licensed antimicrobials and for which few, if any, potentially effective drugs are identifiable in the late-stage development pipeline.
American Journal of Medicine, 1989
A case-control study was performed to identify and quantify risk factors for amphotericin B-assoc... more A case-control study was performed to identify and quantify risk factors for amphotericin B-associated nephrotoxicity. Thirty-five patients receiving intravenous amphotericin B for treatment of proven or suspected fungal infection who developed nephrotoxicity (greater than 100% increase in baseline serum creatinine to a level above the normal range) were compared with 60 control patients receiving amphotericin B who did not develop nephrotoxicity. Amphotericin B dosing variables and other potential risk factors were analyzed in a logistic regression model. Cases of nephrotoxicity received a significantly higher average daily dose of amphotericin B (0.49 +/- 0.18 mg/kg/day) than did controls (0.34 +/- 0.17 mg/kg/day). In a multivariate model, the risk of nephrotoxicity increased 3.7-fold for each 50-mg increase in total dose for a fixed duration of therapy and patient weight. Risk decreased by a factor of 0.4 for each extra day of therapy for a fixed total dose and weight. An increase in weight was also protective when the two other dosage variables were held constant. Each 0.10 mg/kg/day dose increment was associated with a 1.8-fold (95% confidence interval, 1.2 to 2.7) increase in the risk of nephrotoxicity. Other significant risk factors included diuretic use during amphotericin B therapy (12.5, 1.7 to 94.7), for which a linear dose-response relationship was demonstrated, and an abnormal baseline serum creatinine level (15.4, 1.4 to 173.2). Risk factors for amphotericin B-associated nephrotoxicity include higher average daily doses (approximately a doubling for each 0.10 mg/kg/day increment), diuretic use, and abnormal baseline renal function. These data suggest possible protective interventions and will aid clinicians in assessing the risk-benefit ratio of amphotericin B therapy for deep fungal infection.
American Journal of Medicine, 1989
The purpose of this study was to define risk factors for nosocomial candidemia in adult patients ... more The purpose of this study was to define risk factors for nosocomial candidemia in adult patients without leukemia at a tertiary care medical center. All patients with nosocomial candidemia between August 1, 1981, and October 31, 1984, were included if they met strict selection criteria and did not have acute or chronic leukemia. For each case, one control was selected from among patients admitted during the same month/year and matched for hospital service and duration of hospitalization up to the first blood culture that grew Candida species. Logistic regression was used to obtain estimates of risk after simultaneously controlling for other variables. Candida albicans caused 24 of the 48 fungemias studied. The risk factors identified included the presence of a central line (odds ratio, 26.4; 95% confidence interval, 1.5 to 451.1); bladder catheter (13.0 1.3 to 131.4); two or more antibiotics (25.1, 2.1 to 318); azotemia (22.1, 2.2 to 223.2); transfer from another hospital (21.3, 1.7 to 274.5); diarrhea (10.2, 1.03 to 101.4); and candiduria (27.0, 1.7 to 423.5). A prior surgical procedure was associated with lowered risk (0.1, 0.01 to 0.9), suggesting perhaps that medical service patients are at higher risk than those on surgical services. Because total parenteral nutrition was always administered by means of a central line, it could not be shown to increase the risk over that conferred by a central line alone. This study has defined seven major risk factors for nosocomial candidemia. These findings should facilitate development of rational approaches to preventing infection and may assist clinicians in identifying those patients in whom this life-threatening complication is likely to occur.
American Journal of Medicine, 1985
Dental Traumatology, 1988
Abstract Survival of bacteria in periapical tissues may be the reason for endodontic failures. Th... more Abstract Survival of bacteria in periapical tissues may be the reason for endodontic failures. This case report describes the treatment of a patient with periapical lesions refractory to endodontic treatment. Microbiological sampling from fistulae associated with the lesions revealed the presence of Pseudomonas aeruginosa. Phenoxymethyl penicillin, metronidazole and carbenicillin were ineffective in eliminating the periapical infection. However, an investigational antibiotic, Ciprofloxacin, which was administered orally twice daily for 15 weeks, proved to be an effective, safe and convenient medicament in the treatment of periapical Pseudomonas aeruginosa infection. The fistulae closed in less than 2 weeks and a radiograph taken during the fourteenth week of therapy showed healing of the apical periodontitis with osseous regeneration. It is suggested that Ciprofloxacin is a valuable agent in the treatment of apical periodontitis, and probably other odontogenic infections caused by susceptible aerobic gram-negative bacilli.
Infection Control and Hospital Epidemiology, 1990
The hospital-wide attack rate for Clostridium difficile-associated diarrhea at our tertiary-care ... more The hospital-wide attack rate for Clostridium difficile-associated diarrhea at our tertiary-care university hospital was 0.02 per 100 patient discharges (0.02%) in 1982, but 0.41% and 1.47% in 1986 and 1987, respectively, with a peak incidence of 2.25% in the fourth quarter of 1987. Hospital antibiotic usage patterns showed concurrent increased use of third-generation cephalosporins, and intravenous vancomycin and metronidazole. Thirty-seven cases selected for study were older than 37 control patients, more likely to have an underlying malignancy and less likely hospitalized on the obstetrics/gynecology service. Their mean duration of hospitalization prior to diagnosis was 21 days, versus a mean total length of stay of eight days for controls. All cases received antibiotics, compared to 24 of the controls. Cases were given more antibiotics for longer periods, and more often received clindamycin, third-generation cephalosporins, aminoglycosides and vancomycin. Gender, race, duration of hospitalization, prior surgery and antiulcer therapy were not significant by logistic regression analysis. Epidemiologic variables with significantly different adjusted odds ratios (95% confidence intervals) were age greater than 65 years (14.1, 1.4-141), intensive care unit residence (39.2, 2.2-713), gastrointestinal procedure (23.2, 2.1-255) and more than ten antibiotic days (summation of days of each antibiotic administered) (16.1, 2.2-117). Control measures included encouraging earlier isolation and treatment of suspected cases and formulary restriction of clindamycin, with use of metronidazole for therapy of anaerobic infections. By the second half of 1988, the attack rate had dropped progressively to 0.74%.
Infection Control and Hospital Epidemiology, 1988
An epidemic of adenovirus 7a in our neonatal intensive care nursery and intermediate care nursery... more An epidemic of adenovirus 7a in our neonatal intensive care nursery and intermediate care nursery in July and August 1987 caused the death of two patients. Significant symptomatic infection possibly due to the virus occurred in nine patients, ten staff, and three parents, of whom three patients, three staff, and one parent were positive by culture. As a direct consequence of the outbreak, 58 staff days of work were lost; the intensive care nursery had to be closed to admissions for 19 days and the intermediate care nursery for 14 days. Seventeen newborns were transferred to other hospitals and four mothers were sent elsewhere for delivery. Control measures, which included cohorting of patients, use of gloves, gowns and goggles, and exclusion of symptomatic staff from the unit, appeared effective. Rapid immunofluorescence testing of virological specimens was of little use in monitoring the outbreak, largely because of poor specimen quality. This outbreak further underlines the ease of transmission and high morbidity of neonatal adenovirus infection.
American Journal of Medicine, 1984
The utility and safety of fiberoptic bronchoscopy in the diagnosis of invasive pulmonary aspergil... more The utility and safety of fiberoptic bronchoscopy in the diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia have not been examined. The results of 21 bronchoscopic procedures in 19 patients with invasive pulmonary aspergillosis and acute leukemia were reviewed. Analysis was confined to the 16 patients who had histopathologically documented infection on biopsy or at autopsy. Fiberoptic bronchoscopy established or suggested the diagnosis of invasive pulmonary aspergillosis in eight of 16 (50 percent) patients. Transbronchial or bronchial biopsy added only one diagnosis to those obtained by bronchial washing and brushing. Although fiberoptic bronchoscopy was a safe and well-tolerated procedure in our patients with invasive pulmonary aspergillosis and acute leukemia, its success rate was only 50 percent overall, and it appeared to be even less successful when performed early in the course of the disease. Fiberoptic bronchoscopy is a useful first procedure for the evaluation of patients with acute leukemia and possible invasive pulmonary aspergillosis, but a negative result does not exclude aspergillosis. Further diagnostic procedures, including repeated bronchoscopy, or institution of empiric antifungal therapy may be warranted if the clinical suspicion of invasive pulmonary aspergillosis is high.
Pediatric Infectious Disease Journal, 1988
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Infection Control and Hospital Epidemiology, 1989
We reviewed 402 hospital admissions of patients with acute leukemia to define the frequency and c... more We reviewed 402 hospital admissions of patients with acute leukemia to define the frequency and characteristics of anaerobic bacteremia in this patient population. Six (5.2%) of the 116 septicemia episodes documented in these patients were caused by anaerobes (Bacteroides species, 3; Fusobacterium species, 2; and Clostridium tertium, 1); two of these episodes were polymicrobial. Five patients had had prior bacteremia. All six patients were receiving broad-spectrum antibiotics, including an anti-pseudomonal penicillin, at the time of the episode. In each instance, the absolute granulocyte count was 0/mm3. Five patients had clinically apparent sources of infection, including perirectal abscess, gastrointestinal bleeding, or Clostridium difficile-associated diarrhea. Anaerobic bacteremia is an infrequent occurrence in granulocytopenic patients with acute leukemia, but may occur when there is obvious disruption of normal gastrointestinal anatomic barriers.
Pediatric Infectious Disease Journal, 1988
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Clinical Therapeutics, 1997
Community-acquired pneumonia remains an important infectious disease problem, with more than 4 mi... more Community-acquired pneumonia remains an important infectious disease problem, with more than 4 million cases occurring in the United States annually. Although Streptococcus pneumoniae remains the most commonly identified organism, a variety of bacterial and nonbacterial pathogens may be involved. Hospitalization is unnecessary in most cases, and oral antibiotic therapy is common. In the majority of cases, the etiology of pneumonia is unknown at the time of presentation, necessitating the use of empiric therapy. Quinolones have not been utilized in this setting in the past because of their inconsistent coverage of S pneumoniae. Sparfloxacin (RP 64206) is a broad-spectrum fluoroquinolone with excellent activity in vitro against the majority of bacteria involved in community-acquired pneumonia, including pneumococcus. We therefore studied the efficacy and safety of sparfloxacin compared with the second-generation cephalosporin cefaclor as empiric therapy for patients with community-acquired pneumonia in a double-masked, double-dummy, multicenter trial. Three hundred thirty patients aged 18 years or older with community-acquired pneumonia suspected of being bacterial in etiology were enrolled at 74 centers in the United States from June 1, 1992, to March 4, 1995. Patients meeting the inclusion criteria were randomized to receive 10 days of either sparfloxacin 400 mg orally once followed by sparfloxacin 200 mg orally daily (n = 168), or cefaclor 500 mg orally every 8 hours (n = 162). There were no significant differences between groups with regard to baseline characteristics. Patients were followed up serially at 4 +/- 1 days, 20 +/- 3 days, and 38 +/- 7 days after the beginning of therapy. Patients were evaluated for clinical response, clinical recurrence of infection, and eradication of baseline pathogens. The primary efficacy variable was the clinical response (cured or improved) in the subgroup of patients meeting the definition of clinically assessable. Responses were also evaluated in the intent-to-treat population. In the intent-to-treat population, 35.7% of patients receiving sparfloxacin were clinically cured, compared with 32.1% of patients receiving cefaclor. Clinical successes (patients clinically cured plus improved) were also comparable (72.6% of patients in the sparfloxacin group and 71.0% of patients in the cefaclor group). Similar clinical success rates were noted using only the clinically assessable population (primary efficacy variable). Forty-four percent of patients receiving sparfloxacin and 39.1% of patients receiving cefaclor were clinically cured. In the sparfloxacin group, 86.6% of patients were clinical successes, compared with 84.4% of patients in the cefaclor group. Microbiologic cures were comparable in both groups. There was no difference in the incidence of recurrence of infection or superinfection. Adverse events thought to be due to study drug occurred equally in both groups (14.3% in the sparfloxacin group vs 14.8% in the cefaclor group). Results show that sparfloxacin is a safe and effective empiric therapy for patients with community-acquired pneumonia and is comparable to cefaclor.
Expert Review of Anti-infective Therapy, 2008
The emergence of new human pathogens and increasing antimicrobial resistance in well-established ... more The emergence of new human pathogens and increasing antimicrobial resistance in well-established pathogens are critical public health concerns. Unfortunately, the pipeline of new antimicrobial candidates remains remarkably lean for molecules active against increasingly problematic Gram-negative bacterial pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa. Although a number of new anti-Gram-negative antibacterial agents are likely to be introduced soon for clinical use, they will not represent a quantum leap in our ability to effectively treat these human pathogens of great concern. New classes of antimicrobials with novel mechanisms of action and new approaches to increasing the effectiveness of traditional antimicrobials are urgently needed. Renewed research and development efforts must become a priority, lest we fall further behind in our therapeutic initiatives.