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  • American Society for Microbiology  (13)
  • English  (13)
  • 1
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    Online Resource
    Efficacy of Liposomal Amphotericin B with Prolonged Circulation in Blood in Treatment of Severe Pulmonary Aspergillosis in Leukopenic Rats
    American Society for Microbiology ; 2000
    In:  Antimicrobial Agents and Chemotherapy Vol. 44, No. 3 ( 2000-03), p. 540-545
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 44, No. 3 ( 2000-03), p. 540-545
    Abstract: The therapeutic efficacy of long-circulating polyethylene glycol-coated liposomal amphotericin B (AMB) (PEG-AMB-LIP) was compared with that of AMB desoxycholate (Fungizone) in a model of severe invasive pulmonary aspergillosis in persistently leukopenic rats as well as in temporarily leukopenic rats. PEG-AMB-LIP treatment (intravenous administration) consisted of a single, or double (every 72 h), or triple (every 72 h) dose of 10 mg of AMB/kg of body weight, a double dose (every 72 h) of 14 mg of AMB/kg, or a 5-day treatment (every 24 h) with 6 mg/kg/dose. AMB desoxycholate was administered for 10 consecutive days at 1 mg of AMB/kg/dose. Treatment was started 30 h after fungal inoculation, at which time mycelial growth was firmly established. Both persistently and temporarily leukopenic rats died between 4 and 9 days after Aspergillus fumigatus inoculation when they were left untreated or after treatment with a placebo. In persistently leukopenic rats, a single dose of PEG-AMB-LIP (10 mg/kg) was as effective as the 10-day treatment with AMB desoxycholate (at 1 mg/kg/dose) in significantly prolonging the survival of rats infected with A. fumigatus and in reducing the dissemination of A. fumigatus to the liver. Prolongation of PEG-AMB-LIP treatment (double or triple dose or 5-day treatment) did not further improve efficacy. For temporarily leukopenic rats no major advances in efficacy were achieved compared to those for persistently leukopenic rats, probably because the leukocyte numbers in blood were restored too late in the course of infection.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.44.3.540-545.2000
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2000
    detail.hit.zdb_id: 1496156-8
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  • 2
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    Consequences of Noncompliance for Therapy Efficacy and Emergence of Resistance in Murine Tuberculosis Caused by the Beijing Genotype of Mycobacterium tuberculosis
    American Society for Microbiology ; 2012
    In:  Antimicrobial Agents and Chemotherapy Vol. 56, No. 9 ( 2012-09), p. 4937-4944
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 56, No. 9 ( 2012-09), p. 4937-4944
    Abstract: Despite great effort by health organizations worldwide in fighting tuberculosis (TB), morbidity and mortality are not declining as expected. One of the reasons is related to the evolutionary development of Mycobacterium tuberculosis , in particular the Beijing genotype strains. In a previous study, we showed the association between the Beijing genotype and an increased mutation frequency for rifampin resistance. In this study, we use a Beijing genotype strain and an East-African/Indian genotype strain to investigate with our mouse TB model whether the higher mutation frequency observed in a Beijing genotype strain is associated with treatment failure particularly during noncompliance therapy. Both genotype strains showed high virulence in comparison to that of M. tuberculosis strain H37Rv, resulting in a highly progressive infection with a rapid lethal outcome in untreated mice. Compliance treatment was effective without relapse of TB irrespective of the infecting strain, showing similar decreases in the mycobacterial load in infected organs and similar histopathological changes. Noncompliance treatment, simulated by a reduced duration and dosing frequency, resulted in a relapse of infection. Relapse rates were correlated with the level of noncompliance and were identical for Beijing infection and East African/Indian infection. However, only in Beijing-infected mice, isoniazid-resistant mutants were selected at the highest level of noncompliance. This is in line with the substantial selection of isoniazid-resistant mutants in vitro in a wide isoniazid concentration window observed for the Beijing strain and not for the EAI strain. These results suggest that genotype diversity of M. tuberculosis may be involved in emergence of resistance and indicates that genotype-tailor-made treatment should be investigated.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00124-12
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2012
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  • 3
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    Chitinase Induction Prior to Caspofungin Treatment of Experimental Invasive Aspergillosis in Neutropenic Rats Does Not Enhance Survival
    American Society for Microbiology ; 2018
    In:  Antimicrobial Agents and Chemotherapy Vol. 62, No. 1 ( 2018-01)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 62, No. 1 ( 2018-01)
    Abstract: Host chitinases, chitotriosidase and acidic mammalian chitinase (AMCase), improved the antifungal activity of caspofungin (CAS) against Aspergillus fumigatus in vitro . These chitinases are not constitutively expressed in the lung. Here, we investigated whether chitosan derivatives were able to induce chitinase activity in the lungs of neutropenic rats and, if so, whether these chitinases were able to prolong survival of rats with invasive pulmonary aspergillosis (IPA) or of rats with IPA and treated with CAS. An oligosaccharide-lactate chitosan (OLC) derivative was instilled in the left lung of neutropenic rats to induce chitotriosidase and AMCase activities. Rats instilled with OLC or with phosphate-buffered saline (PBS) were subsequently infected with A. fumigatus and then treated with suboptimal doses of CAS. Survival, histopathology, and galactomannan indexes were determined. Instillation of OLC resulted in chitotriosidase and AMCase activities. However, instillation of OLC did not prolong rat survival when rats were subsequently challenged with A. fumigatus . In 5 of 7 rats instilled with OLC, the fungal foci in the lungs were smaller than those in rats instilled with PBS. Instillation of OLC did not significantly enhance the survival of neutropenic rats challenged with A. fumigatus and treated with a suboptimal dosage of CAS. Chitotriosidase and AMCase activities can be induced with OLC, but the presence of active chitinases in the lung did not prevent the development of IPA or significantly enhance the therapeutic outcome of CAS treatment.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00960-17
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2018
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  • 4
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    The Therapeutic Effect of Tigecycline, Unlike That of Ceftazidime, Is Not Influenced by whether the Klebsiella pneumoniae Strain Produces Extended-Spectrum β-Lactamases in Experimental Pneumonia in Rats
    American Society for Microbiology ; 2013
    In:  Antimicrobial Agents and Chemotherapy Vol. 57, No. 1 ( 2013-01), p. 643-646
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 57, No. 1 ( 2013-01), p. 643-646
    Abstract: The efficacies of tigecycline and ceftazidime against fatal pneumonia in rats caused by an extended-spectrum β-lactamase (ESBL)-positive Klebsiella pneumoniae strain or its wild-type (WT) progenitor were compared. Ceftazidime at 12.5 or 50 mg/kg of body weight twice daily (b.i.d.) was effective (50% or 100% rat survival) in pneumonia caused by the WT isolate but unsuccessful (100% rat mortality) in pneumonia caused by the ESBL-positive variant. In contrast, tigecycline at 6.25, 12.5, or 25 mg/kg b.i.d. showed dosage-dependent efficacy up to 100% rat survival irrespective of the ESBL character of the infecting organism.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01154-12
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2013
    detail.hit.zdb_id: 1496156-8
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  • 5
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    Tigecycline Potentiates Clarithromycin Activity against Mycobacterium avium In Vitro
    American Society for Microbiology ; 2016
    In:  Antimicrobial Agents and Chemotherapy Vol. 60, No. 4 ( 2016-04), p. 2577-2579
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 60, No. 4 ( 2016-04), p. 2577-2579
    Abstract: The in vitro activities of clarithromycin and tigecycline alone and in combination against Mycobacterium avium were assessed. The activity of clarithromycin was time dependent, highly variable, and often resulted in clarithromycin resistance. Tigecycline showed concentration-dependent activity, and mycobacterial killing could only be achieved at high concentrations. Tigecycline enhanced clarithromycin activity against M. avium and prevented clarithromycin resistance. Whether there is clinical usefulness of tigecycline in the treatment of M. avium infections needs further study.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.02864-15
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
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  • 6
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    Improved Efficacy of Ciprofloxacin Administered in Polyethylene Glycol-Coated Liposomes for Treatment of Klebsiella pneumoniae Pneumonia in Rats
    American Society for Microbiology ; 2001
    In:  Antimicrobial Agents and Chemotherapy Vol. 45, No. 5 ( 2001-05), p. 1487-1492
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 45, No. 5 ( 2001-05), p. 1487-1492
    Abstract: Animal and clinical data show that high ratios of the area under the concentration-time curve and the peak concentration in blood to the MIC of fluoroquinolones for a given pathogen are associated with a favorable outcome. The present study investigated whether improvement of the therapeutic potential of ciprofloxacin could be achieved by encapsulation in polyethylene glycol (PEG)-coated long-circulating sustained-release liposomes. In a rat model of unilateral Klebsiella pneumoniae pneumonia (MIC = 0.1 μg/ml), antibiotic was administered at 12- or 24-h intervals at twofold-increasing doses. A treatment period of 3 days was started 24 h after inoculation of the left lung, when the bacterial count had increased 1,000-fold and some rats had positive blood cultures. The infection was fatal within 5 days in untreated rats. Administration of ciprofloxacin in the liposomal form resulted in delayed ciprofloxacin clearance and increased and prolonged ciprofloxacin concentrations in blood and tissues. The ED 50 (dosage that results in 50% survival) of liposomal ciprofloxacin was 3.3 mg/kg of body weight/day given once daily, and that of free ciprofloxacin was 18.9 mg/kg/day once daily or 5.1 mg/kg/day twice daily. The ED 90 of liposomal ciprofloxacin was 15.0 mg/kg/day once daily compared with 36.0 mg/kg/day twice daily for free ciprofloxacin; 90% survival could not be achieved with free ciprofloxacin given once daily. In summary, the therapeutic efficacy of liposomal ciprofloxacin was superior to that of ciprofloxacin in the free form. PEG-coated liposomal ciprofloxacin was well tolerated in relatively high doses, permitting once daily administration with relatively low ciprofloxacin clearance and without compromising therapeutic efficacy.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.45.5.1487-1492.2001
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2001
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  • 7
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    Ciprofloxacin in Polyethylene Glycol-Coated Liposomes: Efficacy in Rat Models of Acute or Chronic Pseudomonas aeruginosa Infection
    American Society for Microbiology ; 2002
    In:  Antimicrobial Agents and Chemotherapy Vol. 46, No. 8 ( 2002-08), p. 2575-2581
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 46, No. 8 ( 2002-08), p. 2575-2581
    Abstract: In a previous study in experimental Klebsiella pneumoniae pneumonia, the therapeutic potential of ciprofloxacin was significantly improved by encapsulation in polyethylene glycol-coated (“pegylated”) long-circulating (STEALTH) liposomes. Pegylated liposomal ciprofloxacin in high doses was nontoxic and resulted in relatively high and sustained ciprofloxacin concentrations in blood and tissues, and hence an increase in the area under the plasma concentration-time curve (AUC). These data correspond to data from animal and clinical studies showing that for fluoroquinolones the AUC/MIC ratio is associated with favorable outcome in serious infections. Clinical failures and the development of resistance are observed for marginally susceptible organisms like Pseudomonas aeruginosa and for which sufficient AUC/MIC ratios cannot be achieved. In the present study the therapeutic efficacy of pegylated liposomal ciprofloxacin was investigated in two rat models of Pseudomonas aeruginosa pneumonia. In the acute model pneumonia developed progressively, resulting in a rapid onset of septicemia and a high mortality rate. Ciprofloxacin twice daily for 7 days was not effective at doses at or below the maximum tolerated dose (MTD). However, pegylated liposomal ciprofloxacin either at high dosage or given at low dosage in combination with free ciprofloxacin on the first day of treatment was fully effective (100% survival). Obviously, prolonged concentrations of ciprofloxacin in blood prevented death of the animals due to early-stage septicemia in this acute infection. However, bacterial eradication from the left lung was not effected. In the chronic model, pneumonia was characterized by bacterial persistence in the lung without bacteremia, and no signs of morbidity or mortality were observed. Ciprofloxacin administered for 7 days at the MTD twice daily resulted in killing of more than 99% of bacteria in the lung; this result can also be achieved with pegylated liposomal ciprofloxacin given once daily. Complete bacterial eradication is never observed.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.46.8.2575-2581.2002
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2002
    detail.hit.zdb_id: 1496156-8
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  • 8
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    Effect of Treatment Duration on Pharmacokinetic/Pharmacodynamic Indices Correlating with Therapeutic Efficacy of Ceftazidime in Experimental Klebsiella pneumoniae Lung Infection
    American Society for Microbiology ; 2006
    In:  Antimicrobial Agents and Chemotherapy Vol. 50, No. 9 ( 2006-09), p. 2919-2925
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 50, No. 9 ( 2006-09), p. 2919-2925
    Abstract: The pharmacokinetic/pharmacodynamic (PK/PD) indices that define the therapeutic effect of the beta-lactam ceftazidime in a rat model of Klebsiella pneumoniae lung infection were investigated in relation to treatment duration and treatment endpoint. Treatment was started 24 h after infection with dosing regimens of 3.1 up to 1,600 mg/kg of body weight/day and dosing every 6, 12, or 24 h. When animals were treated for a relatively short period of 48 h, the duration of time that unbound plasma ceftazidime levels exceeded the MIC of the antibiotic for the infecting strain was the index that best correlated with therapeutic efficacy in terms of significant bacterial killing in the infected lung (microbiological effect). The maximum effect was reached when plasma ceftazidime levels were above the MIC for 60 to 70% of the dosing interval. However, when the treatment duration was extended to a relatively long period of 18 days instead of 48 h and animal survival rate instead of microbiological efficacy was taken as the endpoint, the f AUC/MIC ratio (where AUC is the area under the concentration-time curve) was the PK/PD index that best correlated with therapeutic efficacy. The PK/PD indices that effect 50% survival of rats for the f AUC/MIC ratios were 18.0 (95% confidence interval [95% CI], 16.3 to 19.9), 20.2 (95% CI, 13.8 to 29.4), and 27.9 (95% CI, 21.3 to 36.5) for the schedules of administration of every 6, 12, and 24 h, respectively. The f AUC/MIC needed for 100% survival was 〉 100. We conclude that the PK/PD index that best correlates with outcome is dependent on the duration of treatment and/or the parameter of outcome. The effect of long-term treatment should be studied more extensively in other models of infection.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00859-05
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2006
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  • 9
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    Therapeutic Efficacy of Liposome-Encapsulated Gentamicin in Rat Klebsiella pneumoniae Pneumonia in Relation to Impaired Host Defense and Low Bacterial Susceptibility to Gentamicin
    American Society for Microbiology ; 2001
    In:  Antimicrobial Agents and Chemotherapy Vol. 45, No. 2 ( 2001-02), p. 464-470
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 45, No. 2 ( 2001-02), p. 464-470
    Abstract: Long-circulating liposomes (LCL) may be used as targeted antimicrobial drug carriers as they localize at sites of infection. As a result, LCL-encapsulated gentamicin (LE-GEN) has demonstrated superior antibacterial activity over the free drug in a single-dose study of immunocompetent rats with Klebsiella pneumoniae pneumonia. In the present study, the therapeutic efficacy of LE-GEN was evaluated by monitoring rat survival and bacterial counts in blood and lung tissue in clinically relevant models, addressing the issue of impaired host defense and low bacterial antibiotic susceptibility. The results show that in immunocompetent rats infected with the high-GEN-susceptibility K. pneumoniae strain, a single dose of LE-GEN is clearly superior to an equivalent dose of free GEN. Yet complete survival can also be obtained with multiple doses of free GEN. In leukopenic rats infected with the high-GEN-susceptible K. pneumoniae strain, free GEN at the maximum tolerated dose (MTD) was needed to obtain survival. However, with the addition of a single dose of LE-GEN to free-GEN treatment, complete survival can be obtained using a sevenfold-lower cumulative amount of GEN than with free-GEN treatment alone. In leukopenic rats infected with low-GEN-susceptible K. pneumoniae cells, free GEN at the MTD did not result in survival. The use of LE-GEN is needed for therapeutic success. Increasing LE-GEN bilayer fluidity resulted in an increased GEN release from the liposomes and hence improved rat survival, thus showing the importance of the liposome lipid composition for therapeutic efficacy. These results warrant further clinical studies of liposomal formulations of aminoglycosides in immunocompromised patients with severe infections.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.45.2.464-470.2001
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2001
    detail.hit.zdb_id: 1496156-8
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  • 10
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    Caspofungin Prolongs Survival of Transiently Neutropenic Rats with Advanced-Stage Invasive Pulmonary Aspergillosis
    American Society for Microbiology ; 2008
    In:  Antimicrobial Agents and Chemotherapy Vol. 52, No. 4 ( 2008-04), p. 1345-1350
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 52, No. 4 ( 2008-04), p. 1345-1350
    Abstract: A high-dose-step-down strategy for caspofungin treatment was evaluated in an experimental model of advanced-stage invasive pulmonary aspergillosis. The therapeutic efficacy of caspofungin in relation to the severity of invasive pulmonary infection caused by Aspergillus fumigatus in transiently neutropenic rats was investigated by using rat survival and the decrease in the fungal burden as the parameters of efficacy. When treatment was started at either 16 h or 24 h after fungal inoculation, caspofungin administered intraperitoneally at 4 mg/kg of body weight/day for 10 days was highly effective (100% and 93% rat survival, respectively). However, only 27% rat survival was obtained when treatment was started at 72 h, when the rats had advanced-stage infection. Increasing the dose from 4 to 10 mg/kg/day could compensate for the decrease in efficacy and resulted in 67% rat survival. The high dose of 10 mg/kg/day for 10 days did not appear to be necessary since a high-dose-step-down dosing schedule with 10 mg/kg/day for 3 days followed by 4 mg/kg/day for 7 days was equally effective. At 10 days after the end of treatment with 10 mg/kg/day caspofungin, the level of neither A. fumigatus DNA nor A. fumigatus galactomannan in the infected left lung was significantly decreased. In contrast, A. fumigatus galactomannan concentrations in serum were significantly decreased. The levels of creatinine, blood urea nitrogen, alanine aminotransferase, and asparate aminotransferase were not elevated during treatment. Caspofungin is effective for the treatment of invasive pulmonary aspergillosis in transiently neutropenic rats and is even effective in rats with advanced-stage infection. In this model, the administration of high-dose-step-down treatment was as effective as treatment with high doses for the whole treatment period.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00536-07
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2008
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