Doripenem in hospital infections: a focus on nosocomial pneumonia, complicated intra-abdominal infections, and complicated urinary tract infections

Abstract

Doripenem is the latest carbapenem on the market to date. Although not an antibiotic in a new class, it offers a glimmer of hope in combating serious infections secondary to multidrug-resistant Gram-negative bacteria when we have not seen a new class of antibacterial, particularly for Gram-negative bacteria, for more than 10 years. In vitro, doripenem exhibits a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including extended-spectrum β-lactamase (ESBL) and Amp-C β-lactamase producing Enterobacteriaceae and anaerobes. Doripenem also exhibits better in vitro activity against Pseudomonas aeruginosa compared to other anti-pseudomonal carbapenems. It combines the desirable activities of both imipenem and meropenem. It has similar activity to imipenem against Gram-positive pathogens and has the antimicrobial spectrum of meropenem against Gram-negative organisms. Several randomized clinical trials have demonstrated that doripenem is non-inferior to meropenem, imipenem, piperacillin/tazobactam, or levofloxacin in its efficacy and safety profile in treating a wide range of serious bacterial infections including intra-abdominal infection, complicated urinary tract infection, and nosocomial pneumonia. Due to its wide spectrum of activity and good safety profile it is susceptible to misuse leading to increasing rates of resistance. Judicious use should be considered when using doripenem as a first-line agent or drug of choice for serious infections. Doripenem is a well-tolerated drug with common adverse effects including headache, nausea and diarrhea. Caution should be used in patients with hypersensitivity to carbapenems and adverse reactions to β-lactam agents. Dosage adjustment is needed for patients with renal impairment. Doripenem has demonstrated economic and clinical benefits. It has been shown to reduce hospital length of stay and duration of mechanical ventilation for intensive care unit (ICU) patients. Therefore, doripenem is a welcome addition to our limited armamentarium of antibiotics available to treat serious bacterial infections in hospitalized patients.

Clinical Experience of Patients Receiving Doripenem-Containing Regimens for the Treatment of Healthcare-Associated Infections

“…Additionally, the clinical success rate was 89.4% and ranged from 70.3% to 100.0%. Our findings are in line with the findings of a review [16] of several clinical trials conducted by Lo et al and a recent meta-analysis [17], both of which reported that doripenem was not inferior to the comparators, such as meropenem, imipenem, piperacillin/tazobactam, or levofloxacin, in its efficacy and safety profile in patients with a wide range of serious hospital-acquired infections. Thus, these results suggest that doripenem may serve as an effective treatment option in the armamentarium of antibiotics available to treat HCAIs.…”

“…The microbiological response to doripenem observed in the present work was similar to that reported in the study conducted by Vazquez et al in which favorable microbiological responses were achieved in 71.4% of the 35 microbiologically evaluable patients receiving imipenem treatment for complicated urinary tract infection in a hospitalized adult population [19]. Therefore, both our findings and those of previous reports [16,18] suggest that doripenem may be as useful as other carbapenems for the treatment of hospital-associated urinary tract infections.…”

A meta-analysis of efficacy and safety of doripenem for treating bacterial infections

“…This study suggests that doripenem use may be beneficial both economically and clinically to patients. 15 The current meta-analysis suggests that there is no significant difference between doripenem and comparator drugs on treatment efficacy and safety, but doripenem remains a valuable alternative as it has several advantages. First, a total daily dose of 1.5 g of doripenem is equivalent to 3 g of meropenem or 2-3 g of imipenem in terms of clinical and microbiological cure rates.…”

A Review of Doripenem for the Treatment of Serious Bacterial Infections

“…Doripenem-treated patients compared with imipenem-treated patients showed reductions in median LOS (24 vs. 37 days), median ICU LOS (15 vs. 17 days), and median time on mechanical ventilation (7 vs. 13 days). Lo and colleagues 132 confirm these findings, suggesting the broad spectrum of activity and efficacy of doripenem contribute to relative cost benefits (including significantly reduced LOS and time needed on mechanical ventilation) that may make it the drug of choice in the treatment of serious nosocomial infections. Further studies with larger samples are warranted to test the hypothesis that doripenem improves medical resource utilization in VAP patients with P. aeruginosa infection.…”