C H Nightingale

Hartford Hospital, Hartford, Connecticut, United States

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Publications (179)629.41 Total impact

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    D P Niclau · p R Tessier · I Rubinstein · C H Nightingale
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    ABSTRACT: In addition to bactericidal activity, macrolide antibacterials possess clinically relevant properties such as immunomodulatory activity. Whether such activity extends to novel antibacterials that are structurally related to macrolides, such as the ketolides, remains largely unknown. The objective of this study was to evaluate the in vivo immunomodulatory profile of the first ketolide antibacterial - telithromycin in a murine neutropenic thigh infection model. Specific pathogen-free, female ICR mice were rendered transiently neutropenic with intraperitoneal cyclophosphamide. Thighs were inoculated with 10(6) colony-forming units of a single clinical isolate of Streptococcus pneumoniae. Once inoculated, mice (n=500) received single oral doses of telithromycin (10, 25 or 50 mg/kg of body weight) or no treatment (control). Blood was obtained via cardiac puncture prior to and at 2, 4, 8, and 24 h after dose administration for determination of cytokine concentrations. Significant post-inoculation elevations of interleukin (IL)-1beta, IL-6, and IL-10 were noted in untreated controls over 24 h. Telithromycin attenuated these increases and the suppression of both IL-6 and IL-10 release was observed to be dose dependent. Systemic concentrations of IL-2 and tumor necrosis factor alpha showed an upward trend over the initial 8-h post-inoculation period in the telithromycin group. These data therefore reveal novel in vivo immunomodulatory effects of telithromycin. Further studies are warranted to determine whether such effects contribute to the therapeutic efficacy of the drug in patients with acute respiratory tract infections.
    Pharmazie 05/2006; 61(4):343-7. · 1.05 Impact Factor
  • C T Ong · P K Dandekar · C Sutherland · C H Nightingale · D P Nicolau
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    ABSTRACT: Antimicrobial efficacy is dependent on the ability of the agent to reach the site of infection. To assess the bronchopulmonary drug disposition of a novel ketolide, telithromycin (TEL), the epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations were utilized as a surrogate marker for lung penetration. Adult subjects scheduled for diagnostic bronchoscopy received oral TEL 800 mg once daily for 5 days. Plasma and bronchoalveolar lavage (BAL) samples were collected 2, 8, 12, or 24 h after the last TEL dose. TEL concentrations in the ELF and AM were determined using a validated HPLC assay. ELF drug concentrations were calculated using the urea dilution method. Seventeen subjects with a mean age 65 +/- 13 years and a mean weight of 81 +/- 25 kg completed this open-label study. The median (range) TEL concentrations in plasma and ELF, respectively, were 1.09 mg/l (1.00-4.81) and 3.91 mg/l (2.64-9.59) at 2 h (n = 6), 0.48 and 1.09 mg/l at 8 h (n = 1), 0.65 mg/l (0.18-1.55) and 1.81 mg/l (0.61-10.0) at 12 h (n = 5), and 0.11 mg/l (0.09-0.24) and 0.69 mg/l (0.15-1.58) at 24 h (n = 5). The median AM concentrations obtained from these subjects were 53.35 mg/l at 2 h, 32.55 mg/l at 8 h, 65.96 mg/l at 12 h, and 26.43 mg/l at 24 h. Overall TEL was well tolerated. No discontinuation was required due to an adverse event. TEL displayed high intrapulmonary penetration with ELF concentrations exceeding that of plasma at all time points. AM intracellular concentrations were multiple times higher than in the ELF and plasma. These data support the clinical efficacy of TEL against intracellular and extracellular pathogens, particularly with Streptococcus pneumoniae having an MIC(90 )well below achievable concentrations at the site of infection.
    Chemotherapy 11/2005; 51(6):339-46. DOI:10.1159/000088958 · 1.29 Impact Factor
  • C H Nightingale
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    ABSTRACT: This study compared the quality of 65 generic clarithromycin products manufactured in 18 countries with that of the innovator product. To assess quality, the generic products were examined visually, assayed by high-pressure liquid chromatography for clarithromycin content and impurities, tested for dissolution properties, and compared with the innovator product manufactured by Abbott Laboratories. This survey found that many generic clarithromycin products were not equivalent to the innovator product and many of these generic products fell short of the approved specifications developed for the innovator product. Overall, 9% (6 of 65) of all generic tablets tested failed to contain between 95% and 105% of the clarithromycin claimed in the label, thus falling short of the approved registered specification for the innovator product. Seventeen percent (1 of 6) of tablets from Latin America (LA), 8% (3 of 38) of tablets from the Asia, Africa, Pacific (AAP) region, and 10% (2 of 21) of tablets from Europe did not contain the amount of clarithromycin drug content claimed in the label. A total of 34% (17 of 50) of the generic products tested released less drug in 30 minutes than did the innovator tablets. Although the majority of these generic products met the dissolution specification requiring that 80% of the drug must dissolve in 30 minutes, one generic product failed to meet this specification with 68% of drug dissolving in 30 minutes. Moreover, 19% (12 of 65) of all the generic products tested exceeded the Abbott Laboratories' 3% limit for total impurities in bulk drug, and 30% (20 of 65) exceeded the Abbott Laboratories' 0.8% limit for the known impurity 6,11 di-O-methyl erythromycin A. These results demonstrated that generic tablets are often not comparable in vitro to the innovator product. These findings suggest that results achieved with branded clarithromycin (Abbott Laboratories) should not be extrapolated to generic products. In vivo studies would be needed to determine the clinical relevance of these findings.
    Clinical Drug Investigation 02/2005; 25(2):135-52. DOI:10.2165/00044011-200525020-00006 · 1.56 Impact Factor
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    ABSTRACT: Daptomycin has demonstrated in vitro activity against gram-positive organisms, including Streptococcus pneumoniae. However, the pharmacodynamic (PD) profile of daptomycin is needed to relate the activity of the drug to biologically achievable concentrations. The PD profile of daptomycin against four S. pneumoniae isolates was determined using the immunocompromised murine thigh model. Due to the high protein binding of this agent, PD parameters were calculated based on free drug exposures. Efficacy was assessed by the change in log colony-forming units (CFU) in thighs after 24 h of drug treatment. Daptomycin produced a 7.1 (95% confidence interval 7.0-7.2) log(10) CFU kill. The ratio between overall drug exposure and the minimum inhibitory concentration (MIC) (AUC/MIC) was the most predictive of the PD parameters. The S. pneumoniae AUC/MIC required for static effects was 12 (95% confidence interval 10-14). Eighty percent and 99% of maximal kill was achieved at ratios of 35 (95% confidence interval 32-39) and 184 (95% confidence interval 160-208), respectively. Clinically achievable serum drug exposures produced by the lowest dose of daptomycin currently studied in humans (4 mg/kg/day) should result in a potent in vivo bactericidal effect against infections due to S. pneumoniae such as bacteremia, where serum drug concentrations adequately reflect the concentration at the site of infection.
    Chemotherapy 05/2004; 50(1):11-6. DOI:10.1159/000077278 · 1.29 Impact Factor
  • N R Florea · B Capitano · C H Nightingale · D Hull · G J Leitz · D P Nicolau
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    ABSTRACT: Itraconazole is often given for fungal prophylaxis to renal transplant recipients, who require concomitant cyclosporine in the immediate posttransplant period. We determined the extent of the pharmacokinetic interaction between cyclosporine and itraconazole oral solution in renal transplant recipients and the effect on daily drug costs. This was a single-center, open-label, nonrandomized study. Posttransplantation, renal transplant recipients received itraconazole solution 200 mg twice daily and cyclosporine, dosed to achieve target concentrations. Once at steady state, blood samples were collected over 12 hours for pharmacokinetic evaluation of cyclosporine, itraconazole, and hydroxy-itraconazole. Itraconazole was discontinued after approximately a 3-month prophylaxis regimen. Cyclosporine doses were titrated to achieve target concentrations and cyclosporine concentrations were once again determined when steady state was achieved. A noncompartmental analysis was used to analyze cyclosporine pharmacokinetic parameters. The pharmacoeconomic impact was measured based on the percent change in dose of cyclosporine when administered with and without itraconazole. Drug costs were calculated using the average wholesale price. The cost per patient, as well as the average cost, was calculated for the cyclosporine/itraconazole combination, as well as the cyclosporine regimen alone. Eight renal transplant recipients completed the study. All were included for itraconazole analyses and seven for cyclosporine analyses. Mean peak and trough itraconazole levels were 1.64 +/- 0.82 and 1.23 +/- 0.90 microg/mL respectively. Mean peak and trough hydroxy-itraconazole levels were 2.37 +/- 1.55 and 2.20 +/- 1.48 microg/mL, respectively. While on itraconazole, a 48% reduction in the mean total daily dose of cyclosporine was necessary to maintain target concentrations (171 +/- 63.6 versus 329 +/- 103.5 mg, P =.003). This reduction in cyclosporine dose resulted in a discounted itraconazole daily drug cost of approximately 29.5%. Administering itraconazole with cyclosporine allows for a decrease in the cyclosporine dose, thus lowering daily drug costs and providing adequate antifungal coverage with itraconazole and hydroxy-itraconazole trough concentrations above the MIC(90) of Candida and Aspergillus spp.
    Transplantation Proceedings 01/2004; 35(8):2873-7. DOI:10.1016/j.transproceed.2003.10.058 · 0.98 Impact Factor
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    ABSTRACT: To describe the pharmacodynamic profile of daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) and Enterococci species based on bacterial density in an immunocompromised mouse thigh infection model. The pharmacodynamic (PD) profile of daptomycin was determined against two MRSA, one vancomycin-resistant Enterococcus faecium, and one vancomycin-susceptible Enterococcus faecalis using the immunocompromised murine thigh model. Efficacy was assessed by the change in log10 cfu in thighs after 24 h of drug treatment. Daptomycin produced a maximal kill of 4.5-5 log10 cfu against the MRSA and 1.5-2 log10 for the Enterococcus species. AUC/MIC was the most predictive of the PD parameters. Utilizing MICs determined in serum or broth in the calculation of the PD parameters had minimal effect on this correlation. AUCfree/MICbroth required for static effects with MRSA and Enterococcus species were 12-36 and 5-13, whereas 99% of maximal kill was achieved at ratios of 171-442 and 38-157, respectively. These data reveal the potent in vivo bactericidal activity of daptomycin against MRSA and Enterococcus species using clinically achievable drug exposures (dose 4-6 mg/kg per day) currently under investigation in man.
    Journal of Antimicrobial Chemotherapy 10/2003; 52(3):405-11. DOI:10.1093/jac/dkg337 · 5.31 Impact Factor
  • M K Kim · M A Banevicius · M Zhong · X Shi · M Hu · C H Nightingale · D P Nicolau
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    ABSTRACT: Quinupristin-dalfopristin (Q/D) is often utilized in critically ill patients, some of whom require CVVH. This study was undertaken to determine the clearance of O/D and their main active metabolites (RPR 100391, RP 69012, RP 12536) via CVVH in the swine model. Q/D 7.5 mg/kg was intravenously administered over 0.5 h to 12 swine after induction of acute renal failure by ligation of the renal arteries. At 0.5 h post injection, the CVVH procedure was initiated and continued for 8 hours at the following pump rates: (1)100 mL/min, (2)180 rnL/min, and (3)100 mL/min with dialysis (flow rate: 1 L/h). Blood and ultrafiltrate samples were collected at 1 h intervals and assessed by a validated HPLC method. Plasma analysis suggests rapid metabolism to the main active metabolites which are appreciably cleared as demonstrated by high clearance and sieving coefficient estimates. Mean clearance estimates for RP 69012, RP 100391, and RP 12536 are 729, 777, and 578 mL/h in the 100 mL/min CVVH group, 772, 785, 685 mL/min in the 180 mL/min CVVH group, and 753, 791, 616 mL/min in the 100 mL/min CVVH group with 1 L/h dialysis, respectively. These data reveal that Q/D is rapidly metabolized and the metabolites are cleared to a large extent via CVVH. Due to the considerable contribution of the metabolites to overall in vivo activities, additional studies are required to fully quantify their removal before final dosage modifications for patients undergoing CVVH can be recommended.
    The International journal of artificial organs 02/2002; 25(1):33-9. · 0.96 Impact Factor
  • M K Kim · D Xuan · R Quintiliani · C H Nightingale · D P Nicolau
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    ABSTRACT: A multiple-dose, open-labelled, randomized, two period crossover human volunteer study was performed (i) to describe the pharmacokinetic profile and safety profile of piperacillin and tazobactam (P/T) administered 6.0/0.75 g and 8.0/1.0 g q12h and (ii) to characterize the pharmacodynamic profile of these regimens against a variety of common targeted pathogens. Blood samples were collected after the third dose and concentrations of P/T were determined by a validated high-performance liquid chromatography assay. Pharmacokinetic profiles of P/T were determined by non-compartment analysis. Percentage time above the MIC (%T > MIC) of piperacillin was calculated for a range of MICs. In this study, no adverse events were attributed after multiple administrations of either 6.0/0.75 g or 8.0/1.0 g dose regimens. The peak concentration, half-life and area under the curve (AUC0-(0-tau)) of piperacillin were significantly different by a paired t-test (P < 0.05) between the two study regimens. The trough concentration, half-life and area under the curve (AUC0-(0-tau)) of tazobactam were substantially different from parameters reported previously for conventional regimens. The 8.0/1.0 g regimen provided 50% T > MIC for MICs < or =32 mg/L, while a similar value for the 6.0/0.75 g regimen was < or = 16 mg/L. High-dose P/T regimens with extended interval were well tolerated and provide adequate dynamic exposure for a variety of susceptible pathogens.
    Journal of Antimicrobial Chemotherapy 09/2001; 48(2):259-67. · 5.31 Impact Factor
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    ABSTRACT: The pharmacodynamic parameters of peak serum drug concentration/MIC (peak/MIC) ratio and the area under the curve (AUC)/MIC ratio have been used to characterize in vivo drug exposure and its relationship to bacterial killing for the fluoroquinolones. Our study objectives were to describe the pharmacodynamic relationship between gatifloxacin exposure and outcome as assessed by bacterial density and survival in an immunocompromised murine thigh model of pneumococcal infection and to assess the relationship between drug exposure and these outcomes in an immunocompetent host. ICR mice were rendered neutropenic, and thigh infection was induced by intramuscular administration of 0.1 ml of 10(5) to 10(7) CFU of Streptococcus pneumoniae/ml. Mice received 1 to 5 mg of uranyl nitrate/kg of body weight at day -3 and were randomized to receive 10 to 80 mg of gatifloxacin/kg every 6 to 24 h orally, starting at 2 h postinoculation. Bacterial density studies were completed 24 h after initiation of therapy, and survival was assessed after 4 days of treatment. MICs for clinical isolates (n = 8) ranged from 0.25 to 1.0 microg/ml. Correlations were assessed between the change in bacterial density, as well as survival, and the AUC/MIC ratio, peak/MIC ratio, and the duration of time that serum drug concentration remained above the MIC. The best predictor of bacterial response was the AUC/MIC ratio for both outcome measures. There was greater efficacy, as measured by a decrease in log change in CFU as well as by survival data, in the immunocompetent mice compared to the immunocompromised mice. These data demonstrate (i) the appropriateness of the AUC/MIC ratio as a dynamic predictor of response to pneumococcal infection for the fluoroquinolones, (ii) that gatifloxacin AUC/MIC ratios of 30 to 40 appear to optimize bactericidal activity and survival in this model, and (iii) that immunocompetency of the host plays a role in efficacy.
    Antimicrobial Agents and Chemotherapy 08/2001; 45(7):2092-7. DOI:10.1128/AAC.45.7.2092-2097.2001 · 4.48 Impact Factor
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    ABSTRACT: The role of moxifloxacin and levofloxacin pharmacokinetics (PK) in antimicrobial efficacy and in the selection of fluoroquinolone-resistant Streptococcus pneumoniae strains was investigated using the rabbit tissue cage abscess model. A rabbit tissue cage was created by insertion of sterile Wiffle balls in the dorsal cervical area. Animals orally received a range of moxifloxacin or levofloxacin doses that simulate human PK for 7 days 48 h after the Wiffle balls were inoculated with fluoroquinolone-sensitive S. pneumoniae (10(7) CFU). Abscess fluid was collected on a daily basis over 14 days to measure bacterial density and MICs. Moxifloxacin regimens produced a range of area under the concentration-time curve (AUC)/MIC ratios ranging from 9.2 to 444 and peak/MIC ratios ranging from 1.3 to 102. Levofloxacin doses produced AUC/MIC ratios of 5.1 to 85.5 and peak/MIC ratio of 0.9 to 14.8. Moxifloxacin at 6.5, 26, and 42 mg/kg reduced the bacterial log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 4.2 +/- 2.2 (20%), 5.8 +/- 0.4 (100%), and 5.4 +/- 0.4 (100%), respectively, over the dosing period. Levofloxacin at 5.5, 22, and 32 mg/kg reduced the log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 2.8 +/- 0.7 (20%), 5.1 +/- 1.3 (80%), and 4.6 +/- 1.3 (60%), respectively. Moxifloxacin has a greater bactericidal rate as determined by regression of log CFU versus time data. The AUC/MIC and peak/MIC ratios correlated with the efficacy of both drugs (P < 0.05). Resistance to either drug did not develop with any of the doses as assessed by a change in the MIC. In conclusion, data derived from this study show that moxifloxacin and levofloxacin exhibit rapid bactericidal activity against S. pneumoniae in vivo, and moxifloxacin exhibits enhanced bactericidal activity compared to levofloxacin, with AUC/MIC and peak/MIC ratios correlated with antimicrobial efficacy for both drugs. The development of fluoroquinolone-resistant S. pneumoniae was not observed with either drug in this model.
    Antimicrobial Agents and Chemotherapy 04/2001; 45(3):794-9. DOI:10.1128/AAC.45.3.794-799.2001 · 4.48 Impact Factor
  • W. Zhou · C.H. Nightingale · G.A. Davis · D.P. Nicolau
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    ABSTRACT: The study was undertaken to evaluate the single-dose absorption, elimination, and systemic bioavailability of enterally administered fluconazole relative to intravenous fluconazole in ICU patients. Fluconazole pharmacokinetics were evaluated in five patients who had normal gastrointestinal motility, normal renal and hepatic function. A single 200 mg dose of fluconazole was administered either as an intravenous infusion over 1 h or the suspension given via a feeding tube in a crossover design. Fluconazole serum concentrations were determined by a validated HPLC method and the pharmacokinetic parameters of fluconazole were calculated using non-compartmental analysis. The absolute bioavailability of the suspension as determined by a ratio AUC susp/AUC IV was 77.4±44%.
    Journal of Infectious Disease Pharmacotherapy 01/2001; 5(1):27-35.
  • D Xuan · J F Lu · D P Nicolau · C H Nightingale
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    ABSTRACT: The population pharmacokinetics of tobramycin was investigated in a group of 327 adult hospitalized patients receiving once-daily administration of tobramycin at a dose of 7 mg kg(-1). The patients had an average age of 57+/-18 y and an average weight of 65+/-14 kg; 153 of the patients were female. Data, comprised of 575 serum concentrations, were analyzed using a nonlinear mixed-effect model (NONMEM) with a first-order conditional estimation method and were best described with a one-compartment model. The patient covariates including body weight, gender, age and creatinine clearance (CL(CR)) were added in a stepwise fashion to identify their potential influences on tobramycin pharmacokinetics. Results showed that tobramycin clearance (CL) was linearly correlated with CL(CR) (proportionality constant: 0.066+/-0.002 x CL(CR) (ml min(-1))) and the volume of distribution (Vd) was linearly related to body weight (proportionality constant: 0.40+/-0.024 x body weight (1 kg(-1))). The mean population estimates for CL and Vd were 4.53 l h(-1) and 27.3 l, respectively. The half-life of tobramycin was estimated to be 4.2 h. The inter-individual variability in CL and Vd were 37.0 and 28.5%, respectively. The residual error was 1.2 mg l(-1). Based on the results, optimal dosing intervals for renal impaired patients were calculated and were comparable with the intervals derived from the previous established nomogram.
    International Journal of Antimicrobial Agents 09/2000; 15(3):185-91. DOI:10.1016/S0924-8579(00)00172-2 · 4.30 Impact Factor
  • C O Onyeji · D P Nicolau · C H Nightingale · L Bow
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    ABSTRACT: It has been demonstrated previously that, in non-neutropenic animals, interferon-gamma markedly enhances the efficacies of gentamicin and vancomycin against Enterococcus faecalis resistant to these antibiotics. The aim of our study was to determining whether granulocyte colony-stimulating factor (G-CSF) can be beneficial as an adjunct to gentamicin and vancomycin in the treatment of the same infection in neutropenic mice. After induction of neutropenia by cyclophosphamide, mice were inoculated ip with the organism. The infected animals received sc administrations of G-CSF, antibiotic or a combination of both agents at determined dosing regimens. Infected animals treated with G-CSF alone showed a dose-dependent increase in survival. The inoculum size used in establishing infection affected the effectiveness of the cytokine. Survival was significantly (P: < 0.01) better in the infected animals given gentamicin and vancomycin plus G-CSF than in those given antibiotics or G-CSF alone. The possibility of pharmacokinetic interaction between G-CSF and each of the antibiotics was examined. The cytokine significantly increased the plasma clearance of gentamicin, with a resultant decrease in the area under the concentration-time curve (AUC), while the disposition of vancomycin was not affected. This study suggests that G-CSF may be a useful adjunct to gentamicin and vancomycin for the treatment of multidrug-resistant E. faecalis infection in neutropenic patients.
    Journal of Antimicrobial Chemotherapy 09/2000; 46(3):429-36. DOI:10.1093/jac/46.3.429 · 5.31 Impact Factor
  • E M Grant · M K Zhong · P G Ambrose · D P Nicolau · C H Nightingale · R Quintiliani
    American Journal of Health-System Pharmacy 06/2000; 57(10):992-5. · 1.88 Impact Factor
  • M K Kim · D P Nicolau · C H Nightingale · R Quintiliani
    Connecticut medicine 05/2000; 64(4):209-12.
  • C H Nightingale
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    ABSTRACT: This study evaluated the quality of 11 generic clarithromycin products obtained in Poland, Slovakia, Slovenia, or Israel and manufactured in Slovenia or Israel. The generic products were examined visually, assayed by high-pressure liquid chromatography for clarithromycin content and impurities, tested for dissolution properties, and compared with the innovator product manufactured by Abbott Laboratories. Fifty-five percent of generic products fell short of the specifications for the innovator product. Ten percent of the generic products did not contain the amount of clarithromycin claimed in the label; 18% released less drug than did the branded tablets in the standard dissolution assay. In light of these results, it is not possible to conclude that all generic tablets are of the same quality as the innovator product; clinical trial results achieved with branded clarithromycin should not be extrapolated to generic products.
    Advances in Therapy 05/2000; 17(3):167-78. DOI:10.1007/BF02853159 · 2.27 Impact Factor
  • J McNabb · R Quintiliani · D P Nicolau · E.D. Grant · C H Nightingale
    Current clinical topics in infectious diseases 02/2000; 20(20):24-42.
  • K Q Bui · MA Banevicius · C H Nightingale · R Quintiliani · D P Nicolau
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    ABSTRACT: Recent in vitro and in vivo data have substantiated the beneficial effects of macrolides/ azalides for use against Pseudomonas aeruginosa. While macrolides/azalides are not very potent in vitro antimicrobial agents against this pathogen, they appear to have an adjunctive role by either altering the course of infection owing to their inhibition of biofilm production or modulation of the host anti-inflammatory response, or both. To determine the in vitro and in vivo effects of clarithromycin as adjunctive therapy with ceftazidime against a mucoidproducing strain of P. aeruginosa, we performed a standard time-kill experiment and a pneumonia model in mice, respectively. Time-kill studies were performed over a 24 h period with varying concentrations of clarithromycin and ceftazidime alone or in combination. Synergic activity was noted with the use of 0.5 x MIC of ceftazidime combined with either 0.5 or 2 x MIC of clarithromycin. Neutropenic mice were infected with 10(8) cfu of mucoid P. aeruginosa intranasally to produce pneumonia and subsequently treated with oral clarithromycin (100 mg/kg) and/or sc ceftazidime (1500 mg/kg) as monotherapy or in combination. The addition of 5 days of clarithromycin to the ceftazidime regimen significantly improved survival as compared with the beta-lactam alone (48% versus 32%, P = 0.04). While a statistically significant difference was not detected with the addition of 3 days of clarithromycin therapy, a trend towards improved survival was noted with this regimen (38% versus 32%). These data demonstrate the adjunctive potential of clarithromycin when administered in combination with an antipseudomonal agent for the treatment of mucoid-producing Pseudomonas in acute respiratory infection.
    Journal of Antimicrobial Chemotherapy 02/2000; 45(1):57-62. DOI:10.1093/jac/45.1.57 · 5.31 Impact Factor
  • J McNabb · R Quintiliani · C H Nightingale · D P Nicolau
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    ABSTRACT: Although ciprofloxacin exhibits more intense microbiological activity against Pseudomonas aeruginosa than does trovafloxacin, the clinical relevance of this observation remains questionable, particularly when the agents are combined with another antipseudomonal agent. To evaluate this further, we conducted a four-way crossover trial to compare the bactericidal activities of ciprofloxacin and trovafloxacin, alone and in combination with cefepime, against three clinical isolates of P. aeruginosa. Healthy subjects received the following regimens, dosed to steady state: trovafloxacin 300 mg/24 h; ciprofloxacin 400 mg/12 h; trovafloxacin 300 mg/24 h plus cefepime 2 g/12 h, and ciprofloxacin 400 mg/12 h plus cefepime 2 g/12 h. Serum bactericidal titers were performed with each regimen. As monotherapy, the area under the bactericidal curve for ciprofloxacin exceeded that of trovafloxacin for all isolates. No significant difference in the overall degree of bactericidal activity was noted for two of three P. aeruginosa isolates for the combination regimens. Additionally, both combination regimens provided bactericidal activity for 100% of the dosing interval for all isolates. These results indicate that, while in vitro differences exist among these quinolones for P. aeruginosa, when a fluoroquinolone is combined with a beta-lactam, this is likely to be of little clinical significance.
    Chemotherapy 01/2000; 46(6):383-9. DOI:10.1159/000007318 · 1.29 Impact Factor
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    D P Nicolau · M A Banevicius · C H Nightingale · R Quintiliani
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    ABSTRACT: While a time-kill methodology noted no appreciable improvement in bactericidal activity with the addition of azithromycin (AZM) to a ceftazidime (CAZ) regimen, data from the murine pneumonia model showed that the addition of AZM significantly improved survival compared to treatment with CAZ alone. These data suggest that AZM might be a useful adjunctive therapy in the management of pneumonia resulting from mucoid isolates of Pseudomonas aeruginosa.
    Antimicrobial Agents and Chemotherapy 01/2000; 43(12):3033-5. · 4.48 Impact Factor

Publication Stats

3k Citations
629.41 Total Impact Points


  • 1975–2006
    • Hartford Hospital
      • Department of Medicine
      Hartford, Connecticut, United States
  • 1999
    • Kansas City VA Medical Center
      Kansas City, Missouri, United States
  • 1977–1999
    • University of Connecticut
      • School of Pharmacy
      Сторс, Connecticut, United States
  • 1995–1996
    • Long Island University
      • Division of Pharmacy Practice
      New York City, New York, United States
  • 1994–1996
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
    • Butler University
      Indianapolis, Indiana, United States
    • University of Hartford
      West Hartford, Connecticut, United States
  • 1988
    • University of Rhode Island
      • College of Pharmacy
      Кингстон, Rhode Island, United States
  • 1978
    • University at Buffalo, The State University of New York
      • Department of Medicine
      Buffalo, New York, United States