Sisomicin: An Aminoglycoside Antibiotic that is Highly Effective against Pseudomonas

The in vitro activity of sisomicin against Pseudomonas is two- to eight-fold greater then gentamicin or amikacin, and similar to tobramycin. Minimal inhibitory concentrations of sisomicin are usually <1.0 μg/ml. Sisomicin interacts synergistically with a variety of penicillins against many Pseudomonas, including strains resistant to gentamicin. The degree of cross-resistance between sisomicin and other aminoglycosides varies depending upon mechanism. Many strains with inactivating enzymes are resistant to sisomicin, gentamicin and tobramycin. However, due to high intrinsic potency, sisomicin is active against many strains that are resistant to other aminoglycosides as a result of impermeability. Thus sisomicin is active against 4% to 66% of strains resistant to gentamicin, tobramycin or amikacin. The ability of sisomicin to protect animals from fatal Pseudomonas infections has been assessed in 29 paired tests with tobramycin and 36 paired tests with gentamicin. The dose of sisomicin in mg/kg required to protect 50% of animals from death is, on average, 1.5 times lower than tobramycin and 3.1 times lower than gentamicin. Sisomicin also interacts synergistically with carbenicillin or ticarcillin in treatment of experimental infections in animals. The human pharmacology of sisomicin is similar to gentamicin. Rates of adverse reactions to sisomicin are comparable to those seen with gentamicin or tobramycin. Clinical trials have shown sisomicin to be as effective, and in some instances more effective, than gentamicin, tobramycin, or amikacin. In several studies, the efficacy of sisomicin, administered in lower doses than gentamicin, was equal to or greater than gentamicin. Infections caused by gentamicin-resistant Pseudomonas have responded to sisomicin. Also, several patients who failed to respond to either gentamicin or tobramycin have been successfully treated with sisomicin. In view of its high intrinsic potency both in vitro and in vivo, sisomicin may become a preferred agent for treatment of serious Pseudomonas infections due to sensitive strains.

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In Vitro Activity of Ferroquine Is Independent of Polymorphisms in Transport Protein Genes Implicated in Quinoline Resistance in Plasmodium falciparum

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00060-08 ◽

2008 ◽

Vol 52 (8) ◽

pp. 2755-2759 ◽

Cited By ~ 43

Author(s):

Maud Henry ◽

Sébastien Briolant ◽

Albin Fontaine ◽

Joel Mosnier ◽

Eric Baret ◽

...

Keyword(s):

Clinical Trials ◽

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Transport Proteins ◽

Vitro Activity ◽

Cross Resistance ◽

In Vitro Activity ◽

Highly Active ◽

In Vitro Response

ABSTRACT The in vitro activity of ferroquine (FQ) (SR97193), a 4-aminoquinoline antimalarial compound that contains a ferrocenic nucleus, against 15 Plasmodium falciparum strains was assessed and compared with those of chloroquine (CQ), quinine (QN), monodesethylamodiaquine (MDAQ), and mefloquine (MQ). These 15 strains were genotyped for polymorphisms in quinoline resistance-associated genes such as Pfcrt, Pfmdr1, Pfmrp, and Pfnhe-1. FQ was highly active against CQ-resistant parasites or in parasites with reduced susceptibility to QN, MDAQ, or MQ. Encouragingly, we did not find a correlation between responses to FQ and those to other quinoline drugs. These results suggest that no cross-resistance exits between FQ and CQ or quinoline antimalarial drugs. Mutations in codons 74, 75, 76, 220, 271, 326, 356, and 371 of the Pfcrt gene; codons 86, 184, 1034, 1042, and 1246 of the Pfmdr1 gene; and codons 191 and 437 of the Pfmrp gene were not significantly associated with P. falciparum susceptibility to FQ. Neither the number of ms4760 DNNND or DDNHNDNHNN repeats in Pfnhe-1 nor the profile of ms4760 was significantly associated with the FQ in vitro response. These data suggest the FQ may not interact with transport proteins in quinoline-resistant parasites. The present results justify further clinical trials of FQ in multidrug resistance areas.

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1592. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa With Overexpression of AmpC β-Lactamase From Phase 3 Clinical Trials

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1772 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S792-S793

Author(s):

Lynn-Yao Lin ◽

Dmitri Debabov ◽

William Chang ◽

Urania Rappo

Keyword(s):

Clinical Trials ◽

Active Agent ◽

Complicated Urinary Tract Infection ◽

Carbapenem Resistance ◽

Vitro Activity ◽

In Vitro Activity ◽

Control Groups ◽

In Vitro Susceptibility ◽

Intra Abdominal Infection

Abstract Background AmpC overproduction is a main mechanism of carbapenem resistance, in the absence of acquired carbapenemases. Ceftazidime-avibactam (CAZ-AVI) has potent in vitro activity against AmpC-producing P. aeruginosa and Enterobacterales that are resistant to carbapenems and other β-lactams. Methods Activity of CAZ-AVI and comparators was evaluated against AmpC-overproducing Enterobacterales (n=77) and P. aeruginosa (n=53) collected from 4 CAZ-AVI clinical trials: RECLAIM (complicated intra-abdominal infection [cIAI]), REPRISE (cIAI/complicated urinary tract infection [cUTI]), RECAPTURE (cUTI) and REPROVE (hospital-acquired pneumonia/ventilator associated pneumonia). In vitro susceptibility of CAZ-AVI and comparators was performed by broth microdilution using ThermoFisher custom panels. CLSI breakpoints were used to determine susceptibility. Quantitative PCR and microarray data were used to characterize presence and expression of AmpC. Clinical response at test of cure was assessed. Results Against 77 AmpC-overproducing Enterobacterales isolates, meropenem-vaborbactam (MVB) (98.7% susceptible [S]), CAZ-AVI (96.1% S), and meropenem (MEM) (96.1% S) had similar in vitro activity (Table), with greater in vitro activity than amikacin (AMK) (84.4% S), gentamicin (61.0% S), and ceftolozane-tazobactam (TZC) (35.1% S). Clinical cures in patients with baseline AmpC-overproducing Enterobacterales were 21/26 (81%) in CAZ-AVI group vs 17/20 (85%) in control groups. Against 53 AmpC-overproducing P. aeruginosa isolates, CAZ-AVI (73.6% S) showed greater in vitro activity than AMK (69.8% S), TZC (58.5% S), and MEM (37.7% S). Clinical cures in patients with baseline AmpC-overproducing P. aeruginosa were 12/14 (86%) in CAZ-AVI group vs 9/12 (75%) in control groups. MIC distributions against the same P aeruginosa isolates were CAZ-AVI (MIC50/90, 4/ >64 µg/mL), MVB (MIC50/90, 8/32 µg/mL), and MEM (MIC50/90, 8/32 µg/mL). Table Conclusion CAZ-AVI was the most active agent against AmpC-overproducing P. aeruginosa with higher proportion of clinical cure than controls. CAZ-AVI was also among the most active agents against AmpC-overproducing Enterobacterales, with >96% isolates susceptible. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee) Urania Rappo, MD, MS, PharmD, Allergan (before its acquisition by AbbVie) (Employee)

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In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01407-05 ◽

2006 ◽

Vol 50 (6) ◽

pp. 2261-2264 ◽

Cited By ~ 36

Author(s):

Hee-Soo Park ◽

Hyun-Joo Kim ◽

Min-Jung Seol ◽

Dong-Rack Choi ◽

Eung-Chil Choi ◽

...

Keyword(s):

Antibacterial Activities ◽

The Other ◽

Vitro Activity ◽

Gram Negative Bacteria ◽

In Vitro Activity ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

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Evaluation of the in vitro activity and in vivo bioavailability of realgar nanoparticles prepared by cryo-grinding

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2006.05.002 ◽

2006 ◽

Vol 29 (1) ◽

pp. 35-44 ◽

Cited By ~ 75

Author(s):

Jin-Zhu Wu ◽

Paul C. Ho

Keyword(s):

Vitro Activity ◽

In Vitro Activity

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In Vitro Activity of Gepotidacin Against Gram-negative and Gram-positive Anaerobes

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02165-21 ◽

2021 ◽

Author(s):

Meredith A. Hackel ◽

James A. Karlowsky ◽

Michele A. Canino ◽

Daniel F. Sahm ◽

Nicole E. Scangarella-Oman

Keyword(s):

Clinical Trials ◽

Vitro Activity ◽

Phase Iii ◽

In Vitro Activity ◽

Gram Positive ◽

Gram Negative ◽

Phase Iii Clinical Trials ◽

Agar Dilution

Gepotidacin (formerly GSK2140944) is a first in class triazaacenaphthylene antibacterial currently in Phase III clinical trials. When tested against Gram-negative ( n =333) and Gram-positive ( n =225) anaerobes by agar dilution, gepotidacin inhibited 90% of isolates (MIC 90 ) at concentrations of 4 and 2 μg/ml, respectively. Given gepotidacin’s in vitro activity against the anaerobic isolates tested, further study is warranted to better understand gepotidacin’s utility in the treatment of infections caused by clinically relevant anaerobic organisms.

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In vivo and in vitro activity of genistein in osteoporosis

Indian Journal of Pharmacology ◽

10.4103/0253-7613.32529 ◽

2007 ◽

Vol 39 (2) ◽

pp. 103 ◽

Cited By ~ 3

Author(s):

Qibing Mei ◽

Jiepin Wang ◽

Fujun Shang ◽

Li Liu ◽

Siwang wang ◽

...

Keyword(s):

Vitro Activity ◽

In Vitro Activity

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1366. In Vitro and In Vivo Activity of Cefiderocol against Stenotrophomonas maltophilia Clinical Isolates

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1197 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S418-S418 ◽

Cited By ~ 2

Author(s):

Akinobu Ito ◽

Merime Ota ◽

Rio Nakamura ◽

Masakatsu Tsuji ◽

Takafumi Sato ◽

...

Keyword(s):

Stenotrophomonas Maltophilia ◽

Systemic Infection ◽

Vitro Activity ◽

Clinical Isolates ◽

Infection Model ◽

In Vitro Activity ◽

In Vivo Efficacy ◽

Broth Microdilution Method

Abstract Background Cefiderocol (S-649266, CFDC) is a novel siderophore cephalosporin against Gram-negatives, including carbapenem (CR)-resistant strains. Its spectrum includes both the Enterobacteriaceae but also nonfermenters, including Stenotrophomonas maltophilia—an opportunistic pathogen with intrinsic resistance to carbapenem antibiotics. In this study, in vitro activity and in vivo efficacy of CFDC and comparators against S. maltophilia were determined. Methods MICs of CFDC and comparators (trimethoprim/sulfamethoxazole (TMP/SMX), minocycline (MINO), tigecycline (TGC), ciprofloxacin (CPFX), cefepime (CFPM), meropenem (MEPM), and colistin (CL)) were determined by broth microdilution method as recommended by CLSI. The MIC against CFDC was determined using iron-depleted cation-adjusted Mueller–Hinton broth. In vivo efficacy of CFDC, CFPM, ceftazidime–avibactam (CAZ/AVI), MEPM, and CL was evaluated using neutropenic murine systemic infection model caused by strain SR21970. The 50% effective doses (ED50s) were calculated by the logit method using the survival number at each dose 7 days after infection. Results MIC90 of CFDC and comparators against the 216 clinical isolates from global countries collected in SIDERO-CR 2014/2016 study are shown in the table. CFDC, TMP/SMX, MINO, and TGC showed good activity with MIC90 of 0.5, 0.25/4.75, 1, and 2 µg/mL, respectively. CFDC, MINO, and TGC inhibited growth of all tested strains at ≤1, ≤4, and ≤8 µg/mL although two strains showed resistance to TMP/SMX. MICs of CFPM, CAZ/AVI, MEPM, and CL were ≥32 µg/mL. The ED50 of CFDC against S. maltophilia SR21970 with MIC of 0.125 mg/mL was 1.17 mg/kg/dose. Conversely, MICs of CFPM, CAZ/AVI, MEPM/CS, and CL against SR21970 were 32 μg/mL or higher, and ED50s were >100 mg/kg/dose, showing that CFDC had potent in vivo efficacy against S. maltophilia strain which was resistant to other antibiotics. Conclusion CFDC showed potent in vitro activity against S. maltophilia, including TMP/SMX-resistant isolates. CFDC also showed potent in vivo efficacy reflecting in vitro activity against S. maltophilia in murine systemic infection model. Disclosures A. Ito, Shionogi & Co., Ltd.: Employee, Salary. M. Ota, Shionogi & Co., Ltd.: Employee, Salary. R. Nakamura, Shionogi & Co., Ltd.: Employee, Salary. M. Tsuji, Shionogi & Co., Ltd.: Employee, Salary. T. Sato, Shionogi & Co., Ltd.: Employee, Salary. Y. Yamano, Shionogi & Co., Ltd.: Employee, Salary.

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