Oral ciprofloxacin plus colistin: prophylaxis against bacterial infection in neutropenic patients. A strategy for the prevention of emergence of antimicrobial resistance

Abstract

Summary. Following a 2-year study, the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance. During a 2-year period (1987±1989), we compared ciprofloxacin 1 colistin (CIP 1 COL) with neomycin 1 colistin (NEO 1 -COL) in a randomized trial ± combinations chosen because of the potential for prophylaxis of Gram-negative infection by ciprofloxacin, with colistin given to reduce the risk of emergence of resistance. Sixty-four patients with similar demographics in each arm were evaluable for efficacy analysis. Patients on CIP 1 COL had a significantly lower proportion of neutropenic days with fever (P , 0´001) and neutropenic days on intravenous antibiotics (P , 0´001) than patients on NEO 1 COL. A total of 54 (15 bacteriologically documented) pyrexial episodes occurred in patients on CIP 1 COL and 77 (41 bacteriologically documented) in patients on NEO 1 COL. Only two Gramnegative bacterial infections occurred in the CIP 1 COL arm compared with 16 in the NEO 1 COL arm. No Staphylococcus aureus infections occurred in the CIP 1 COL group compared with 10 in the other patients. Two CIP-resistant Gram-negative bacilli were isolated from patients on CIP 1 COL compared with 13 NEO-resistant Gram-negative bacilli from patients on NEO 1 COL. Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients, a 2-year follow-up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 350±400 neutropenic episodes. Eight of the 111 (7´2%) isolates were with ciprofloxacin-resistant organisms, involving 2% of the neutropenic episodes, indicating that the strategy of combining colistin with ciprofloxacin has been effective in the prevention of Gram-negative sepsis in neutropenic patients without the emergence of significant resistance despite widespread concurrent hospital and community use of the quinolones.

Antibiotic prophylaxis in neutropenic patients

“…38 Long-term surveillance for the development of ciprofloxacin resistance was conducted after a randomized controlled trial of antibiotic prophylaxis in hematologic patients. 39 After 10 years of continued prophylaxis with ciprofloxacin plus colistin, only 5 ciprofloxacin-resistant, gram-negative bacteria were isolated from 66 episodes of microbiologically documented infection among 47 patients during approximately 700 neutropenic episodes. None of those infections were fatal.…”

The role of antibiotic stewardship in limiting antibacterial resistance among hematology patients

“…A clinical example of de-escalation strategy is shown in the Appendix and illustrates how de-escalation works in an individual patient. For details and background of the prophylaxis strategy in this example, see the method section of the publication by Slobbe et al 17,18 Experience in the Netherlands has shown that broadspectrum empirical therapy in neutropenic fever can also be replaced by narrower-spectrum oral agents, mitigating selection for resistance. De Marie et al and Cornelissen et al reported that intravenous (i.v.)…”

Pharmacokinetics and effects on bowel and throat microflora of oral levofloxacin as antibacterial prophylaxis in neutropenic patients with haematological malignancies

“…However, the systematic use of ciprofloxacin prophylaxis in neutropenic subjects has been clearly associated with the emergence of quinolone-resistant E. coli. [17][18][19][20] Our observation indicates that levofloxacin may be expected to induce resistance in Gram-negative microorganisms to a comparable extent as ciprofloxacin. We used additional prophylaxis with oral colistin in these patients.…”

“…In a recent publication, the addition of colistin to ciprofloxacin appeared to reduce the emergence of quinolone-resistant Gram-negative bacteria and to prevent Gram-negative sepsis in neutropenic patients. 18 In our patients no systemic infections with Gram-negative bacteria occurred.…”