scholarly journals Imipenem and Meropenem: Comparison of In Vitro Activity, Pharmacokinetics, Clinical Trials and Adverse Effects

1998 ◽  
Vol 9 (4) ◽  
pp. 215-228 ◽  
Author(s):  
George G Zhanel ◽  
Andrew E Simor ◽  
Lavern Vercaigne ◽  
Lionell Mandell ◽  
the Canadian Carbapenem Discussion Group
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Data Extraction ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Medline Search ◽  
Serious Infections ◽  
Severe Infections ◽  
Intra Abdominal Infection

OBJECTIVE: To compare and contrast imipenem and meropenem in terms of in vitro activity, pharmacokinetics, clinical efficacy and adverse effects.DATA SELECTION: MEDLINE search from 1975 to 1997 and follow-up of references.DATA EXTRACTION: Clinical trials comparing imipenem with meropenem, or either imipenem or meropenem with standard therapy in the treatment of serious infections were selected.DATA SYNTHESIS: Imipenem, the first carbapenem, was first marketed in 1987; meropenem was introduced to the market in 1996. In general, imipenem is more active against Gram-positive cocci while meropenem is more active against Gram-negative bacilli. The agents display similar pharmacokinetics. Clinical studies in patients with serious infections (intra-abdominal infection, respiratory infection, septicemia, febrile neutropenia) report similar bacteriological and clinical cure rates with imipenem and meropenem. Meropenem is approved for the treatment of bacterial meningitis, whereas imipenem is not. Adverse effects are similar.CONCLUSIONS: Current literature supports the use of imipenem at a dose of 500 mg every 6 h and meropenem at 1 g every 8 h for the treatment of severe infections. For the treatment of serious infections, imipenem (500 mg every 6 h or 2 g/day [$98/day]) is more economical than meropenem (1 g every 8 h or 3 g/day [$142/day]) based on acquisition cost.

scholarly journals 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

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)

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

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.

Cefotaxime: In vitro activity against cephalothin-resistant isolates and use in the treatment of septicemia, pneumonia, urinary tract and other severe infections

Infection ◽  
1981 ◽  
Vol 9 (1) ◽  
pp. 29-33 ◽  
Author(s):  
W. Graninger ◽  
S. Breyer ◽  
H. Pichler ◽  
M. Böhm ◽  
K. H. Spitzy ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Severe Infections

Rifabutin: A Review with Emphasis on its Role in the Prevention of Disseminated Mycobacterium Avium Complex Infection

1994 ◽  
Vol 28 (11) ◽  
pp. 1250-1254 ◽  
Author(s):  
Daniel S. Maddix ◽  
Kimberly B. Tallian ◽  
Paul S. Mead
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Aids Patients ◽  
Double Blind ◽  
Medline Search ◽  
Cd4 Lymphocyte

OBJECTIVE: To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of rifabutin. DATA SOURCES: Pertinent literature published between 1982 and 1993 was identified via a MEDLINE search. Published proceedings of selected conferences were also reviewed. STUDY SELECTION: Selected basic science, microbiologic, and pharmacokinetic articles were evaluated. Because only limited data regarding rifabutin were available in the literature, all clinical trials involving the use of rifabutin in the prevention of Mycobacterium avium complex (MAC) infection in AIDS patients were reviewed. DATA SYNTHESIS: Rifabutin is a rifamycin derivative that was approved recently for the prevention of disseminated MAC disease in patients with advanced HIV infection. The drug has in vitro and in vivo activity against gram-positive bacteria, gram-negative bacteria, and mycobacteria. Two prospective, randomized, double-blind, placebo-controlled, multicenter trials demonstrated that rifabutin decreased the progression to MAC bacteremia in AIDS patients by about 50 percent. Adverse effects that resulted in the discontinuation of rifabutin prophylaxis occurred in 16 percent of patients. Rifabutin induces hepatic enzymes to a lesser extent than does rifampin, but dosage adjustment of drugs that are known to interact with rifampin may be required. CONCLUSIONS: Rifabutin is the only drug shown to be effective in the prevention of MAC bacteremia in AIDS patients; therefore, it should be made available as a formulary agent. It may be reasonable to delay initiation of rifabutin prophylaxis until CD4 lymphocyte counts are less than 75–50/mm3.

Treatment of severe infections due to metallo-β-lactamases-producing Gram-negative bacteria

2020 ◽  
Vol 15 (15) ◽  
pp. 1489-1505
Author(s):  
Matteo Bassetti ◽  
Vincenzo Di Pilato ◽  
Tommaso Giani ◽  
Antonio Vena ◽  
Gian Maria Rossolini ◽  
...  
Keyword(s):  
Observational Studies ◽  
Clinical Development ◽  
Vitro Activity ◽  
Favorable Effect ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Severe Infections ◽  
Important Addition

In the last decades, there was an important paucity of agents for adequately treating infections due to metallo-β-lactamases-producing Gram-negative bacteria (MBL-GNB). Cefiderocol, a novel siderophore cephalosporin showing in vitro activity against MBL-GNB, has been recently marketed, and a combination of aztreonam and ceftazidime/avibactam has shown a possible favorable effect on survival of patients with severe MBL-GNB infections in observational studies. Other agents showing in vitro activity against MBL-GNB are currently in clinical development (e.g., cefepime/taniborbactam, LYS228, cefepime/zidebactam) that could be an important addition to our future armamentarium for severe MBL-GNB infections. Nonetheless, we should not discontinue our efforts to optimize the use of non-β-lactams agents, since they could remain an essential last-resort or alternative option in selected cases.

Sisomicin: An Aminoglycoside Antibiotic that is Highly Effective against Pseudomonas

1981 ◽  
Vol 9 (3) ◽  
pp. 168-176 ◽  
Author(s):  
W Eugene Sanders ◽  
Christine C Sanders
Keyword(s):  
Clinical Trials ◽  
Adverse Reactions ◽  
Aminoglycoside Antibiotic ◽  
Vitro Activity ◽  
Cross Resistance ◽  
In Vitro Activity ◽  
Minimal Inhibitory Concentrations ◽  
Human Pharmacology

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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