Imipenem–Cilastatin and Imipenem–Relebactam
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Imipenem–cilastatin is one of the alternatives of initial antimicrobial therapy for neutropenic fever in high-risk patients. Imipenem has activity against most of the causative pathogens in neutropenic fever, such as P. aeruginosa, Enterobacteriaceae (including ESBL producers), Streptococcus spp., and Entero-coccus faecalis. As noted previously, imipenem will not reliably cover MRSA, MRSE, Enterococcus faecium, and non-bacterial pathogens. Imipenem–cilastatin therapy for neutropenic fever has been supported by substantial clinical experience. There have been 19 RCTs (see Table 37.11) for empirical treatment of neutropenic fever (each of which enrolled more than 100 patients) that compared imipenem–cilastatin with other regimens: cefepime, ceftazidime with or without tobramycin or amikacin, cefoperazone–sulbactam, cefuroxime plus tobramycin, piperacillin–tazobactam, piperacillin plus gentamicin or amikacin, cefoperazone plus piperacillin, ceftazidime plus piperacillin, aztreonam, latamoxef plus tobramy-cin, clinafloxacin, imipenem–cilastatin plus amikacin, and imipenem–cilastatin itself in different dose (Norrby et al., 1987; Liang et al., 1990; Matsui et al., 1991; Winston et al., 1991; Leyland et al., 1992; Rolston et al., 1992; Miller et al., 1993; Erjavec et al., 1994; Freifeld et al., 1995; Aparicio et al., 1996; Bode et al., 1996; Raad et al., 1996; Biron et al., 1998; Bohme et al., 1998; Marra et al., 1998; Winston et al., 1998; Winston et al., 2001; Raad et al., 2003; Cherif et al., 2004). None of these studies showed inferiority of imipenem–cilastatin in clinical success for this condition, and 2 studies demonstrated that imipenem–cilastatin was significantly superior to ceftazidime in clinical success rate (Liang et al., 1990; Rolston et al., 1992).
Impact of tigecycline versus imipenem–cilastatin on fibrinogen levels following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a randomized-controlled study
Published in Journal of Chemotherapy, 2018
Hakeam A. Hakeam, Zainab Al Duhailib, Nawal Salahuddin, Tarek Amin
Generally, antibiotics can alter the coagulation profiles through their effects on gut flora, which normally synthesize vitamin K.32 However, this alteration cannot explain the difference in PT prolongation on day 3 of antibiotic therapy in this study. This is because imipenem–cilastatin is a broad-spectrum antibiotic that exhibits bactericidal activity against a wide range of bacteria, including gut flora. No patients developed major bleeding in this study; hence, fibrinolysis secondary to massive bleeding cannot explain the decreased fibrinogen levels observed with tigecycline use. Recently, it has been shown that tigecycline can inhibit mitochondrial biogenesis in cancer cells from diverse tissues, including the liver, where fibrinogen is normally synthesized.33 It is unknown whether normal hepatic cell mitochondria are inhibited tigecycline exposure. Further investigations are needed to explain the mechanism by which tigecycline affects fibrinogen and other coagulation parameters.
Transient appearance of EDTA dependent pseudothrombocytopenia in a patient with 2019 novel coronavirus pneumonia
Published in Platelets, 2020
Han Li, Bangqin Wang, Leping Ning, Yu Luo, Shulin Xiang
In addition to the antiviral treatment, the patient was also under an antibiotic treatment with Imipenem Cilastatin in ICU. We collected the blood samples in EDTA tubes and monitored the routine blood cell counts. Two days later, we suddenly found a low platelet count of 91 × 109/L. Her platelet count was decreasing progressively from then on. She was treated with platelet infusion twice but failed to respond. In spite of the lowest value of 17 × 109/L, the patient had no signs or symptoms of bleeding. The peripheral blood smear presented platelet aggregation. Meanwhile, the IgG/IgM antibody of SARS-CoV-2 in her serum was conformed qualitatively to be positive. We collected the blood samples with both EDTA tube and citrate tube on the same day. The number of platelet with citrate was normal (118 × 109/L), while that with EDTA was lower with 17 × 109/L. Thus, the patient was diagnosed with EDTA-PCTP. With the remission of COVID-19, the platelet count in the citrate anticoagulant samples remained normal, and the platelet count in the EDTA anticoagulant samples eventually returned to normal (Figure 1). One week after discharged, the patient was negative to the repeated result of IgG/IgM antibody of SARS-CoV-2, and her platelet count in the EDTA anticoagulant samples remained normal.
Advancements in the pharmacological management of sepsis in the elderly
Published in Expert Opinion on Pharmacotherapy, 2023
Christos Psarrakis, Evangelos J. Giamarellos-Bourboulis
Another promising intravenous broad spectrum β-lactamase inhibitor, Durlobactam, is currently being evaluated in combination with sulbactam for infections caused by Acinetobacter baumannii including carbapenem-resistant strains. The part A of the global, non-inferiority, phase III RCT (ATTACK trial) evaluated the clinical efficacy of the novel combination Sulbactam/Durlobactam (SUL-DUR) vs Colistin in 125 patients with pneumonia or bacteremia caused by Acinetobacter baumanii-calcoaceticus complex (ABC). All patients also received imipenem/cilastatin as adjunctive treatment. The primary study endpoint was 28-day all-cause mortality among patients with carbapenem-resistant ABC (CRABC) infections in mMITT population. The preliminary results showed that Sulbactam/Durlobactam was non-inferior to colistin regarding the primary outcome (19% vs 32.3%, difference: −13.2%, 95% CI: −30–3.5%) and was associated with higher clinical cure rate at both EOT (74.6% vs 45.2%, difference: 29.4%, 95% CI: 11.4–47.4) and TOC visits (61.9% vs 40.3%, difference: 21.6%, 95% CI: 2.9–40.3) [100].
Related Knowledge Centers
- Antibiotic
- Endocarditis
- Imipenem
- Pneumonia
- Septic Arthritis
- Urinary Tract Infection
- Pathogenic Bacteria
- Cilastatin
- Sepsis
- Intra-Abdominal Infection