Extended infusion versus intermittent infusion of imipenem in the treatment of ventilator-associated pneumonia

Ibrahim, Mohamed M.; Tammam, Tarek F.; Ebaed, Mohy El Deen; Sarhan, Hatem A.; Gad, Gamal Fadl Mahmoud; Hussein, Amal K.

doi:10.2147/dddt.s143021

Cited by 12 publications

(17 citation statements)

References 25 publications

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“…Ibrahim et al 20 compared the efficacy of imipenem in adult ICU patients with ventilator-associated pneumonia (VAP) following regular infusion over 30-60 minutes (first year of the study) or 3-hour extended infusion (second year of the study). Extended infusion resulted in a significant decrease in mortality, number of recurrent infections, ICU LOS, and the number of mechanical ventilator days.…”

Section: Resultsmentioning

confidence: 99%

Optimal infusion rate in antimicrobial therapy: explosion of evidence in the last five years

Zhu¹,

Zhou²

2018

IDR

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BackgroundSporadic studies in antimicrobial therapy have evaluated the effects of infusion rates on therapeutic and economic outcomes, and new findings may challenge the regular infusion regimen.MethodsFocusing on studies comparing the outcomes of different infusion regimens, the relevant literature was identified by searching PubMed, Web of Science, and Scopus from January 1, 2013 to March 1, 2018. Papers were finally chosen using a PRISMA flowchart.ResultsAntimicrobials with the superiority of prolonged infusion to standard infusion in terms of efficacy and safety include meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin. The strategy of concomitantly reducing total daily dose and prolonging infusion time may cause treatment failure (eg, imipenem). Extended infusion of piperacillin/tazobactam has pharmacoeconomic advantage over standard infusion. Prolonged infusion of voriconazole is inferior to standard infusion because of lower efficacy caused by pharmacokinetic changes. Comparable outcomes following standard infusion and continuous infusion were observed with norvancomycin and nafcillin. Factors determining whether prolonged infusion has a benefit over standard infusion include MIC of bacterial pathogens, bacterial density, diagnosis, disease severity, total daily dose, and renal function.ConclusionTo maximally preserve the effectiveness of current antimicrobials, effective interventions should be implemented to enhance the application of optimal infusion strategies. For reducing nephrotoxicity, prolonged infusion of meropenem is better than conventional infusion in neonates with Gram-negative late-onset sepsis, and continuous infusion of vancomycin is superior to intermittent infusion. For increasing efficacy, prolonged or continuous infusion of time-dependent antimicrobials (eg, meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin) is an optimal choice. Nevertheless, such advantages may only be demonstrated in special clinical circumstances and special populations (eg, patients with a sequential organ failure assessment (SOFA) score≥9, respiratory tract infections, urinary or intra-abdominal infections, or infections caused by less susceptible pathogens would benefit from prolonged infusion of piperacillin/tazobactam).

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Section: Resultsmentioning

confidence: 99%

Optimal infusion rate in antimicrobial therapy: explosion of evidence in the last five years

Zhu¹,

Zhou²

2018

IDR

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“…Characteristics of the studies included in the meta-analysis are described in Table 1. Among nine total studies, two were RCTs (Lyu et al, 2018;Ammar and Abdalla, 2018), three were quasi-experimental studies (Fahimi et al, 2012;Arnold et al, 2013;Bauer et al, 2013) and four were retrospective cohort studies (Lodise et al, 2007;Lee et al, 2012;Ibrahim et al, 2017;Ahmed et al, 2018). The studies spanned three continents (USA, Asia and Africa).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…The conventional II period was 30-60 min and the extended infusion duration was 3-4 h. Five studies used the same total daily doses in both arms. In several studies, the β-lactam doses were adjusted for renal insufficiency (Lodise et al, 2007;Lee et al, 2012;Arnold et al, 2013;Bauer et al, 2013;Ibrahim et al, 2017;Ahmed et al, 2018). None of the studies were funded by pharmaceutical companies.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…None of the studies were funded by pharmaceutical companies. First authors of three trials were contacted for clarification and to complete missing data (Bauer et al, 2013;Ibrahim et al, 2017;Lyu et al, 2018). In two of these three studies, the study authors kindly contributed to data extraction (Bauer et al, 2013;Ibrahim et al, 2017).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Nine studies reported data for all-cause mortality as an outcome with different endpoints; three studies reported inhospital mortality (Fahimi et al, 2012;Bauer et al, 2013;Ibrahim et al, 2017), one reported ICU mortality (Ahmed et al, 2018), one reported ventilator-associated pneumonia-related mortality (Ammar and Abdalla, 2018), two studies reported 30day mortality (Lee et al, 2012;Arnold et al, 2013), one reported 14-day mortality (Lodise et al, 2007), and another study reported 28-day mortality (Lyu et al, 2018) (Table 3). There were 126 deaths among 735 patients in the EI arm compared with 195 deaths among 773 patients in the II arm (RD À0.10; 95% CI À0.15 to À0.04).…”

Section: Mortality Outcomementioning

confidence: 99%

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Comparison of extended versus intermittent infusion of antipseudomonal beta-lactams for the treatment of critically ill patients with respiratory infections: A systematic review and meta-analysis

Aboulatta¹,

Sugita

Wakabayashi

et al. 2020

International Journal of Infectious Diseases

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Objectives: Alternative dosing strategies for β-lactamsthe most common antibiotics used to treat critically ill patients with respiratory tract infectionshave been recommended to maximize the duration of exposure and reduce drug resistance. The objective of this study was to evaluate whether extended infusion of antipseudomonal β-lactams improves mortality and clinical efficacy. Methods: Two independent authors identified eligible trials by searching the PubMed, Cochrane Library, Scopus, and ICHUSHI databases, in both English and Japanese, up to June 2019. Data were extracted from both randomized controlled and observational trials comparing extended infusion (!3 h) with intermittent infusion in critically ill patients. The primary outcome was all-cause mortality. Risk differences (RD) and 95% confidential intervals (CI) were calculated using a random-effects model and subgroup analyses were performed. Sensitivity and heterogeneity were also evaluated. Results: Nine studies involving 1508 participants were included in the meta-analysis. Mortality was lower for extended infusion than for intermittent infusion (RD À0.10; 95% CI À0.15 to À0.04). However, no significant between-group differences in clinical success, length of ICU stay, length of hospital stay, and antibiotic duration were observed. Conclusions: Extended infusions of β-lactams were associated with reduced mortality rates but not with clinical success.

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Machine Learning‐Led Optimization of Combination Therapy: Confronting the Public Health Threat of Extensively Drug Resistant Gram‐Negative Bacteria

Smith,

Nguyen,

Lodise

et al. 2023

Clin Pharma and Therapeutics

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Developing optimized regimens for combination antibiotic therapy is challenging and often performed empirically over many clinical studies. Novel implementation of a hybrid machine‐learning pharmacokinetic/pharmacodynamic/toxicodynamic (ML‐PK/PD/TD) approach optimizes combination therapy using human PK/TD data along with in vitro PD data. This study utilized human population PK (PopPK) of aztreonam, ceftazidime/avibactam, and polymyxin B along with in vitro PDs from the Hollow Fiber Infection Model (HFIM) to derive optimal multi‐drug regimens de novo through implementation of a genetic algorithm (GA). The mechanism‐based PD model was constructed based on 7‐day HFIM experiments across 4 clinical, extensively drug resistant Klebsiella pneumoniae isolates. GA‐led optimization was performed using 13 different fitness functions to compare the effects of different efficacy (60%, 70%, 80%, or 90% of simulated subjects achieving bacterial counts of 102 CFU/mL) and toxicity (66% of simulated subjects having a target polymyxin B area under the concentration‐time curve [AUC] of 100 mg·h/L and aztreonam AUC of 1,332 mg·h/L) on the optimized regimen. All regimens, except those most heavily weighted for toxicity prevention, were able to achieve the target efficacy threshold (102 CFU/mL). Overall, GA‐based regimen optimization using preclinical data from animal‐sparing in vitro studies and human PopPK produced clinically relevant dosage regimens similar to those developed empirically over many years for all three antibiotics. Taken together, these data provide significant insight into new therapeutic approaches incorporating ML to regimen design and treatment of resistant bacterial infections.

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Extended infusion versus intermittent infusion of imipenem in the treatment of ventilator-associated pneumonia

Cited by 12 publications

References 25 publications

Optimal infusion rate in antimicrobial therapy: explosion of evidence in the last five years

Optimal infusion rate in antimicrobial therapy: explosion of evidence in the last five years

Comparison of extended versus intermittent infusion of antipseudomonal beta-lactams for the treatment of critically ill patients with respiratory infections: A systematic review and meta-analysis

Machine Learning‐Led Optimization of Combination Therapy: Confronting the Public Health Threat of Extensively Drug Resistant Gram‐Negative Bacteria

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