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Combined colistin and rifampicin therapy for carbapenem-resistant Acinetobacter baumannii infections: clinical outcome and adverse events

2005; Elsevier BV; Volume: 11; Issue: 8 Linguagem: Inglês

10.1111/j.1469-0691.2005.01198.x

1469-0691

Nicola Petrosillo, M.F. Proietti, Luca Cecchini, M.V. Masala, C. Franchi, Mario Venditti, Silvano Esposito, Emanuele Nicastri, Pierangelo Chinello,

Pneumonia and Respiratory Infections

In the February 2005 issue of Clinical Microbiology and Infection, Michalopoulos et al. [1Michalopoulos AS Tsiodras S Rellos K Mentzelopoulos S Falagas ME Colistin treatment in patients with ICU-acquired infections caused by multi-resistant Gram-negative bacteria: the renaissance of an old antibiotic.Clin Microbiol Infect. 2005; 11: 115-121Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar] concluded that colistin should be considered as a treatment option for critically-ill patients in the intensive care unit with infections caused by multi-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. We have observed previously that rifampicin is active in vitro against A. baumannii, and this led us to investigate the potential therapeutic role of this antimicrobial agent in combination with polymixin B, ampicillin–sulbactam and colistin [2Tascini C Menichetti F Bozza S Del Favero A Bistoni F Evaluation of the activities of two-drug combinations of rifampicin, polymixin B and ampicillin/sulbactam against Acinetobacter baumannii..J Antimicrob Chemother. 1998; 42: 270-271Crossref PubMed Google Scholar, 3Hogg GM Barr JG Webb CH In-vitro activity of the combination of colistin and rifampicin against multidrug-resistant strains of Acinetobacter baumannii..J Antimicrob Chemother. 1998; 41: 494-495Crossref PubMed Scopus (85) Google Scholar, 4Giamarellos-Bourboulis EJ Xirouchaki E Giamarellou H Interactions of colistin and rifampin on multidrug-resistant Acinetobacter baumannii..Diagn Microbiol Infect Dis. 2001; 40: 117-120Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar]. The in-vitro activity of colistin was increased significantly in the presence of rifampicin, and this combination has been proposed for administration in vivo [3Hogg GM Barr JG Webb CH In-vitro activity of the combination of colistin and rifampicin against multidrug-resistant strains of Acinetobacter baumannii..J Antimicrob Chemother. 1998; 41: 494-495Crossref PubMed Scopus (85) Google Scholar,4Giamarellos-Bourboulis EJ Xirouchaki E Giamarellou H Interactions of colistin and rifampin on multidrug-resistant Acinetobacter baumannii..Diagn Microbiol Infect Dis. 2001; 40: 117-120Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar]. However, no data are available on the in-vivo use of colistin–rifampicin against A. baumannii. We would therefore like to describe the clinical outcome of 14 patients infected with carbapenem-resistant A. baumannii who were treated with colistin–rifampicin, as well as the adverse events of this combination. Fourteen critically-ill patients (ten males) with carbapenem-resistant A. baumannii infections, mean age 49 years (median 47 years; range 22–89 years), in the intensive care units of three urban hospitals in Rome, Italy were studied (Table 1). All were receiving mechanical ventilation (mean length of ventilation 28 days; median 16 days; range 5–148 days) and had pneumonia. Carbapenem-resistant A. baumannii was isolated from quantitative cultures of tracheal aspirate from all 14 patients, and was also isolated from the surgical sites of two patients and from the blood of two other patients. All carbapenem-resistant A. baumannii isolates were susceptible to colistin according to the ATB TSE method (bioMérieux, Marcy l'Etoile, France). Intravenous colistin sulphomethate sodium, 2 MU threetimes-daily, adjusted for creatinine clearance, and intravenous rifampicin, 600 mg once-daily, were administered for a mean of 12 days (median 12 days; range 2–24 days). Five of ten patients with ampicillin–sulbactam-susceptible carbapenem-resistant A. baumannii also received intravenous ampicillin–sulbactam. Deterioration in renal function (creatininaemia of up to 2.8 mg/dL) was observed in only one patient, who did not need renal replacement therapy. No other adverse events occurred. Overall, seven (50%) of 14 patients died, five from the Acinetobacter infection, one from Pseudomonas ventilator-associated pneumonia, and one from methicillin-resistant Staphylococcus aureus bloodstream infection. Three patients experienced a relapse of their Acinetobacter infection, and received a second course of colistin–rifampicin; two of these patients died (one from carbapenem-resistant A. baumannii ventilator-associated pneumonia and candidaemia, and the other from Pseudomonas ventilator-associated pneumonia). Thus, therapy with colistin–rifampicin, and with ampicillin–sulbactam in case of susceptibility to this combination, resulted in microbiological clearance of carbapenem-resistant A. baumannii infection in nine (64%) of 14 critically-ill patients, with limited sideeffects. Although the limited number of patients, and the lack of a control group, in this series does not allow a definite conclusion, it seems that the combination of colistin and rifampicin may be an innovative therapeutic option for consideration in the treatment of severe infections caused by carbapenem-resistant A. baumannii.Table 1Acinetobacter baumannii infections in 14 critically-ill patientsPatient no.aPatients 1–3 had Acinetobacter resistant to carbapenems, aminoglycosides and ampicillin–sulbactam; patient 4 had Acinetobacter resistant to carbapenems and amikacin, intermediately resistant to ampicillin–sulbactam, and sensitive only to gentamicin; patients 5–8 had Acinetobacter resistant to carbapenems and amikacin, and sensitive to gentamicin and ampicillin–sulbactam; patients 9–14 had Acinetobacter resistant to carbapenems and aminoglycosides, and sensitive to ampicillin–sulbactam; all isolates were sensitive to colistin.Gender (M/F)Age (years)Acinetobacter infectionAntibiotic therapyOutcomeAntibiotic adverse events1M64VAPC + RRecoveredNone2F89VAPC + RAcinetobacter VAP and candidaemiabDied.None3M73VAPC + RPseudomonas VAPbDied. Cleared AcinetobacterIncrease of creatininaemia 2.8 mg/dL4M25VAP, BSIC + R +A/SRecoveredNone5F36VAPC + RRecoveredNone6M26VAPC + R +A/SRecoveredNone7F65VAPC + RRecoveredNone8M23VAPC + R +A/SRecoveredNone9M26VAP, BSIC + R +A/SAcinetobacter septic shockbDied.None10M83VAPC + RAcinetobacter septic shockbDied.None11M22VAPC + RRecoveredNone12M58VAP, SSIC + R +A/SMRSA BSIbDied. Cleared AcinetobacterNone13M65VAPC + RAcinetobacter VAPbDied.None14F30VAP, SSIC + R +A/SAcinetobacter VAPbDied.NoneBSI, bloodstream infection; VAP, ventilator-associated pneumonia; SSI, surgical site infection; C, colistin; R, rifampicin; A/S, ampicillin–sulbactam.a Patients 1–3 had Acinetobacter resistant to carbapenems, aminoglycosides and ampicillin–sulbactam; patient 4 had Acinetobacter resistant to carbapenems and amikacin, intermediately resistant to ampicillin–sulbactam, and sensitive only to gentamicin; patients 5–8 had Acinetobacter resistant to carbapenems and amikacin, and sensitive to gentamicin and ampicillin–sulbactam; patients 9–14 had Acinetobacter resistant to carbapenems and aminoglycosides, and sensitive to ampicillin–sulbactam; all isolates were sensitive to colistin.b Died. Open table in a new tab BSI, bloodstream infection; VAP, ventilator-associated pneumonia; SSI, surgical site infection; C, colistin; R, rifampicin; A/S, ampicillin–sulbactam.