Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus metronidazole to imipenem/cilastatin for intra-abdominal infections. The Intra-Abdominal Infection Study Group.
OBJECTIVE
In a randomized, double-blind, multicenter trial, ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections. A secondary objective was to demonstrate the ability to switch responding patients from intravenous (IV) to oral (PO) therapy.


BACKGROUND
Intra-abdominal infections result in substantial morbidity, mortality, and cost. Antimicrobial therapy often includes a 7- to 10-day intravenous course. The use of oral antimicrobials is a recent advance due to the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity.


METHODS
Patients were randomized to either ciprofloxacin plus metronidazole intravenously (CIP/MTZ IV) or imipenem intravenously (IMI IV) throughout their treatment course, or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ IV/PO).


RESULTS
Among 671 patients who constituted the intent-to-treat population, overall success rates were as follows: 82% for the group treated with CIP/MTZ IV; 84% for the CIP/MTZ IV/PO group; and 82% for the IMI IV group. For 330 valid patients, treatment success occurred in 84% of patients treated with CIP/MTZ IV, 86% of those treated with CIP/MTZ IV/PO, and 81% of the patients treated with IMI IV. Analysis of microbiology in the 30 patients undergoing intervention after treatment failure suggested that persistence of gram-negative organisms was more common in the IMI IV-treated patients who subsequently failed. Of 46 CIP/MTZ IV/PO patients (active oral arm), treatment success occurred in 96%, compared with 89% for those treated with CIP/MTZ IV and 89% for those receiving IMI IV. Patients who received intravenous/oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment.


CONCLUSIONS
These results demonstrate statistical equivalence between CIP/MTZ IV and IMI IV in both the intent-to-treat and valid populations. Conversion to oral therapy with CIP/MTZ appears as effective as continued intravenous therapy in patients able to tolerate oral feedings.
Solomkin
J S
JS
Department of Surgery, University of Cincinnati College of Medicine, Ohio, 45267-0558, USA.
Reinhart
H H
HH
Dellinger
E P
EP
Bohnen
J M
JM
Rotstein
O D
OD
Vogel
S B
SB
Simms
H H
HH
Hill
C S
CS
Bjornson
H S
HS
Haverstock
D C
DC
Coulter
H O
HO
Echols
R M
RM
D000005:Abdomen; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D015377:Cilastatin / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D002939:Ciprofloxacin / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use; D007239:Infections / Q000188:drug therapy* / Q000382:microbiology; D007262:Infusions, Intravenous; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D004338:Drug Combinations; D008795:Metronidazole; D015377:Cilastatin; D002939:Ciprofloxacin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination