The MAINSTAY for the empirical treatment of serious nosocomial infection
- Extends antibacterial activity against aerobic and anaerobic Gram-positive and Gram-negative bacteria
- A single agent for the treatment of
- – Complicated Intra-Abdominal Infections
- – Nosocomial Pneumonia, including Ventilator-associated Pneumonia
- – Complicated Urinary Tract Infections, Including Pyelonephritis
Doripenem vs meropenem against Pseudomonas and Acinetobacter
Recently, doripenem has been approved for the treatment of nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP). The E-test was performed to determine the MICs of doripenem and meropenem in 203 endotracheal aspirate isolates that consisted of 140 Acinetobacter calcoaceticus-Acinetobacter baumannii complexes and 63 Pseudomonas aeruginosa. Doripenem showed minimum concentration necessary for inhibition of 50% (MIC 50 ) of P. aeruginosa isolates at 0.38 mg/L which is several times (84.2 times) lower than the corresponding MIC 50 value of >32 mg/L for meropenem. The MIC 50 and MIC 90 were similar for both the drugs against A. baumannii. Thus, P. aeruginosa was consistently more susceptible than the A. baumannii.
Keywords: Acinetobacter, doripenem, meropenem, MIC, Pseudomonas
|How to cite this article:
Goyal K, Gautam V, Ray P. Doripenem vs meropenem against Pseudomonas and Acinetobacter. Indian J Med Microbiol 2012;30:350-1
|How to cite this URL:
Goyal K, Gautam V, Ray P. Doripenem vs meropenem against Pseudomonas and Acinetobacter. Indian J Med Microbiol [serial online] 2012 [cited 2017 Oct 22];30:350-1. Available from: http://www.ijmm.org/text.asp?2012/30/3/350/99502
Doripenem is a new parenteral antibiotic from the carbapenem class.  Its antimicrobial spectrum more closely resembles those of meropenem and imipenem than that of ertapenem.  Thus, it has significant in vitro activity against streptococci, methicillin-susceptible staphylococci, Enterobacteriaceae (including extended-spectrum beta- lactamase-producing strains), Pseudomonas aeruginosa, Acinetobacter species, and Bacteroides fragilis. Doripenem has been approved by FDA in 2007 for the treatment of complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI). In Europe and several Asia-Pacific countries such as Thailand, Philippines, Malaysia, Australia and Indonesia, it is also approved for treatment of nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP); a final approval for these indications was obtained in 2008.
|~ Materials and Methods|
We performed the E-test to determine minimum inhibitory concentration (MIC) of doripenem and meropenem in consecutive endotracheal aspirate isolates collected over a period of 6 months from July to Dec 2010 from different patients admitted in ten different intensive care units at Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Pseudomonas aeruginosa and Acinetobacter calcoaceticus–Acinetobacter baumannii complex were selected as these are the two most common multi-drug resistant isolates obtained from VAP patients in PGIMER. For determination of MIC of doripenem and meropenem, E-test strips (bioMerieux India Pvt. Ltd) were used as per the instructions of the manufacturer. The cut-off points for determining MICs were followed according to European Committee on Antimicrobial Susceptibility testing (EUCAST).  Escherichia More Details coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested for quality control, and MICs obtained for these organisms were within the ranges recommended by the EUCAST. An isolate of P. aeruginosa or A. baumannii is susceptible or resistant if its MIC is ≤1 mg/L and ≥4 mg/L respectively for doripenem with no intermediate category defined, and for meropenem breakpoints are susceptible ≤2 mg/L, resistant ≥8 mg/L.
In a previous study, AmpC-β-lactamases and metallo-β-lactamases were produced by 64%, 31% of P. aeruginosa and 47%, 15%, of A. calcoaceticus–A. baumannii complex PGIMER isolates, respectively.  A total of 203 isolates, consisted of 140 (140/203 = 68.9%) A. calcoaceticus–A. baumannii complex and 63 (63/203 = (31%) P. aeruginosa. The majority of A. calcoaceticus–A. baumannii complex isolates were found to be resistant to the majority of other antibiotics as determined by the disk diffusion method (CLSI guidelines, 2010)  i.e. cefotaxime (95%), gentamicin (92%), cefepime (92%), amikacin (88%), ciprofloxacin (87%), ceftazidime (87%), cefoperazone-sulbactam (50%), cefoperazone (45%) and piperacillin-tazobactam (12%). P. aeruginosa showed 100% resistance to cefotaxime, cefoperazone-sulbactam (91%), cefepime (64%), ciprofloxacin (64%), amikacin (62%), ceftazidime (60%), gentamicin (59%), cefoperazone (48%) and piperacillin-tazobactam (18%). Doripenem showed minimum concentration necessary for inhibition of 50% (MIC 50 ) of P. aeruginosa isolates at 0.38 mg/L which is several times (84.2 times) lower than the corresponding MIC 50 value of >32 mg/L for meropenem as shown in [Figure 1]. P. aeruginosa showed sensitivity of 60.3% for doripenem and 44.8% for meropenem. However, doripenem and meropenem were sensitive among 6.4% and 6.3% of A. baumannii isolates, respectively.
|Figure 1: Cumulative distributions of minimum inhibitory concentrations (MICs) for doripenem and meropenem among endotracheal aspirate isolates of Pseudomonas aeruginosa and Acinetobacter calcoaceticus-Acinetobacter baumannii complex|
Doripenem was more effective as compared to meropenem against P. aeruginosa. John et al.  had shown a similar activity of doripenem as compared to meropenem against P. aeruginosa. However, MIC 50 and MIC 90 were same for both the drugs against A. baumannii as shown in [Figure 1]. There were four isolates of A. baumannii and two isolates of P. aeruginosa which were resistant to meropenem and sensitive to doripenem. P. aeruginosa showed sensitivity of 60.3% for doripenem and 44.8% for meropenem. However, doripenem and meropenem were effective against 6.4% and 6.3% of A. baumannii isolates, respectively. Thus, P. aeruginosa were consistently more susceptible than the A. baumannii. Although meropenem is often considered more active in vitro against A. baumannii strains than imipenem or doripenem; , however, in our study, both doripenem and meropenem showed higher rates of resistance among A. baumannii strains. This is the first report from a tertiary care referral hospital on high level of resistance against doripenem in A. baumannii and therefore limits its empirical use in a hospital with high prevalence of MDR A. baumannii. Thus doripenem showed good activity against P. aeruginosa isolates whereas A. baumannii isolates were found to be highly resistant against both the carbapenems. The limitations in this study include the small number of isolates and only in vitro testing has been conducted without clinical correlation. To determine whether these in vitro data translate into superior clinical efficacy, prospectively controlled clinical trials are needed. 
We acknowledge the pharmaceuticals that have provided us E-strips -doripenem (Ranbaxy Intensiva, India); meropenem (Astra Zeneca Pvt. Ltd., India).
This work was supported by Ranbaxy Intensiva, India and Astra Zeneca Pvt. Ltd., India.
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SAFEST in Sensitive Situations
- SAFE with NO treatment-emergent seizures
- Negligible neurotoxic effects