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

Figures & data

Figure 1 Chemical structure of doripenem.

Table 1 In vitro susceptibility of common pathogens to doripenem^2,4,10

Gram-positive microorganisms

Streptococcus constellatus

Streptococcus intermedius

Streptococcus agalactiae Streptococcus pneumoniae

Streptococcus pyogenes

Methicillin-susceptible Staphylococcus aureus

Gram-negative microorganisms

Acinetobacter baumannii

Citrobacter freundii

Enterobacter aerogenes

Enterobacter cloacae

Escherichia coli (including ESBL confirmed spp.)

Haemophilus influenzae (including β-lactamase producing strains)

Klebsiella pneumoniae (including ESBL confirmed spp.)

Klebsiella oxytoca

Moraxella catarrhalis

Morganella morganii

Proteus mirabilis

Pseudomonas aeruginosa

Serratia marcescens

Anaerobic microorganisms

Bacteroides caccae

Bacteroides fragilis

Bacteroides thetaiotaomicron

Bacteroides uniformis

Bacteroides vulgatus

Peptostreptococcus micros

Abbreviation: ESBL, extended spectrum β-lactamase.

Table 2 Pharmacokinetic properties of doripenem following a single 1-hour intravenous infusion of a 500 mg dose administered to healthy participants (N = 24)¹⁰

Property	Value for doripenem
Mean Cmax	23 μg/mL
Mean AUC	36.3 μg·h/mL
Protein binding	8.1%
Volume of distribution	16.8 L
Metabolism	Dehydropeptidase-I
Half-life	∼1 hour

Abbreviations: C_max, maximum concentration; AUC, area under the curve.

Table 3 Manufacturer renal dosage adjustment recommendations¹⁰

Creatinine clearance	Dose
>50 mL/min	No dosage adjustment
≥30 to ≤50 mL/min	250 mg intravenously (over 1 hour) every 8 hours
>10 to <30 mL/min	250 mg intravenously (over 1 hour) every 12 hours
Dialysis	Insufficient information to make dosing recommendations

Table 4 Adverse events reported with doripenem 500 mg IV every 8 hours for treatment in complicated urinary tract infections and intra-abdominal infections in three Phase 3 clinical trials²⁰

Adverse event (N = 853)	Frequency range (%)
Headache	4–16
Nausea	4–12
Diarrhea	6–11
Anemia	2–10
Phlebitis	4–8
Rash	0–5
Pruritus	0–3
Hepatic enzyme elevation	1–2
Vulvomycotic infection	0–2
Oral candidiasis	0–1

FritscheTRStilwellMGJonesRNAntimicrobial activity of doripenem (S-4661): a global surveillance report (2003)Clin Microbiol Infect2005111297498416307551

 PubMed Web of Science ®Google Scholar

PoulakouGGiamarellouHDoripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogensExpert Opin Investig Drugs2008175749771

 PubMed Web of Science ®Google Scholar

Package insert. Doribax® (doripenem for injection)Raritan, NJOrtho-McNeil Pharmaceuticals, Inc2008 Available from www.doribax.com/doribax/shared/pi/doribax.pdf Accessed: January 1, 2009.

 Google Scholar

CadaDLevienTMistryBBakerDDoripenem for InjectionHospital Pharmacy2008432210218

 Google Scholar