Ciprofloxacin Prophylaxis in High Risk Neutropenic Patients
Ciprofloxacin Prophylaxis in High Risk Neutropenic Patients
We analyzed 220 patients (141 in the ciprofloxacin and 79 in the control group) who developed 329 episodes of neutropenia, 219 receiving ciprofloxacin prophylaxis (ciprofloxacin group) and 110 without quinolone prophylaxis (control group). Patients in the ciprofloxacin and control group had similar ages (mean 40 years, range 14 – 82 and 41 years, range 12 – 66, respectively, p=0.56) and gender (60% and 65% of males, respectively, p = 0.28). Ciprofloxacin prophylaxis was given for a mean of 11 days (range 1 – 30, SD ± 4.44), and was started before neutropenia in 94% of episodes, at a mean of 7 days before neutropenia (8 – 23, SD ± 3.49).
Table 1 shows the characteristics and outcomes of the episodes of neutropenia in the two groups. The duration of neutropenia was slightly shorter in the ciprofloxacin group (9 vs. 11 days, p = 0.02). In addition, mucositis (at any grade, but not grades 3 or 4) was less frequent in ciprofloxacin recipients (52% vs. 70%, p = 0.003). Febrile episodes were significantly less frequent in the ciprofloxacin group (73 vs. 93%, p < 0.001), and when present, occurred later in the course of neutropenia (median 4 vs. 2 days after the first day of neutropenia, p < 0.001). While the proportion of episodes classified as FUO and clinically documented infection was similar in the two groups, bacteremia was significantly less frequent in the ciprofloxacin group (22% vs. 33%, p = 0.04). In addition, the mean duration of hospitalization was shorter in the ciprofloxacin group (22 vs. 24 days, p = 0.002), as was the mean duration of antibiotic therapy (8 vs. 11 days, p < 0.001) (Additional file 1).
The rates of clinical or microbiological failure to the empirical treatment with cefepime were similar in the ciprofloxacin and control groups (12% vs. 8% for clinical failures, p = 0.33; and 8.5% and 6% for microbiological failures, p = 0.14; respectively). In addition, no differences were observed in the frequency of glycopeptide use between the two groups. However, carbapenems were given more frequently to ciprofloxacin recipients (36% vs. 14%, p < 0.001).
A total of 98 bacterial isolates were recovered from the 85 episodes of bacteremia. In the ciprofloxacin group, there were 19 episodes with documentation of a single Gram-negative, 22 episodes with a single Gram-positive, and 8 episodes of polymicrobial bacteremia, whereas in the control group there were 13 episodes with documentation of a single Gram-negative, 18 episodes of a single Gram-positive isolate, and 5 episodes of polymicrobial bacteremia (Table 1). Table 2 shows the species distribution of bloodstream isolates in both groups. The most frequent Gram-negative bacteria were E. coli and P. aeruginosa.
Table 3 shows the resistance rates (per 1,000 patients.day) in the two periods. The rate of quinolone-resistant bacteremia (both Gram-positive and Gram-negative) was significantly higher in patients receiving quinolone prophylaxis (6.77 vs. 3.02 per 1,000 patients.day, p = 0.03). In addition, quinolone-resistant enterobacteria were more frequently isolated in period 2 both in cohort patients and in the hematology unit overall (2.12 vs. 0.38 per 1,000 patients.day, p = 0.06 in cohort patients, and 2.54 vs. 0.53 per 1,000 patients.day in the hematology unit, p = 0.004), but remained stable in the hospital (0.76 in period 1 and 0.64 in period 2, p = 0.15). The rates of ESBL production among enterobacteria increased slightly both in cohort patients (0.38 in period vs.1.27 in period 2, p = 0.26) and in the hematology unit (0.52 in period 1 vs. 1.59 in period 2, p = 0.08), and remained stable in the hospital (0.56 in period 1 vs. 0.53 in period 2, p = 0.74). No changes in quinolone resistance among staphylococci were observed in cohort patients.
The genotypic analysis of the isolates from the cohort patients showed a great genetic diversity among isolates recovered from episodes of the cohort, with no similarity between isolates (Figure 1).
(Enlarge Image)
Figure 1.
Molecular analysis of Escherichia coli isolates from cohort patients. A. ERIC2-PCR profiles of Escherichia coli isolates. Lanes 1 and 23: 1 Kb plus molecular size marker; Lanes 2–20: clinical isolates; Lanes 21 and 22: control strains ST69 and ATCC25922. B. Dendrogram of ERIC-2 PCR profiles of Escherichia coli isolates. C: control isolates.
Results
We analyzed 220 patients (141 in the ciprofloxacin and 79 in the control group) who developed 329 episodes of neutropenia, 219 receiving ciprofloxacin prophylaxis (ciprofloxacin group) and 110 without quinolone prophylaxis (control group). Patients in the ciprofloxacin and control group had similar ages (mean 40 years, range 14 – 82 and 41 years, range 12 – 66, respectively, p=0.56) and gender (60% and 65% of males, respectively, p = 0.28). Ciprofloxacin prophylaxis was given for a mean of 11 days (range 1 – 30, SD ± 4.44), and was started before neutropenia in 94% of episodes, at a mean of 7 days before neutropenia (8 – 23, SD ± 3.49).
Table 1 shows the characteristics and outcomes of the episodes of neutropenia in the two groups. The duration of neutropenia was slightly shorter in the ciprofloxacin group (9 vs. 11 days, p = 0.02). In addition, mucositis (at any grade, but not grades 3 or 4) was less frequent in ciprofloxacin recipients (52% vs. 70%, p = 0.003). Febrile episodes were significantly less frequent in the ciprofloxacin group (73 vs. 93%, p < 0.001), and when present, occurred later in the course of neutropenia (median 4 vs. 2 days after the first day of neutropenia, p < 0.001). While the proportion of episodes classified as FUO and clinically documented infection was similar in the two groups, bacteremia was significantly less frequent in the ciprofloxacin group (22% vs. 33%, p = 0.04). In addition, the mean duration of hospitalization was shorter in the ciprofloxacin group (22 vs. 24 days, p = 0.002), as was the mean duration of antibiotic therapy (8 vs. 11 days, p < 0.001) (Additional file 1).
The rates of clinical or microbiological failure to the empirical treatment with cefepime were similar in the ciprofloxacin and control groups (12% vs. 8% for clinical failures, p = 0.33; and 8.5% and 6% for microbiological failures, p = 0.14; respectively). In addition, no differences were observed in the frequency of glycopeptide use between the two groups. However, carbapenems were given more frequently to ciprofloxacin recipients (36% vs. 14%, p < 0.001).
A total of 98 bacterial isolates were recovered from the 85 episodes of bacteremia. In the ciprofloxacin group, there were 19 episodes with documentation of a single Gram-negative, 22 episodes with a single Gram-positive, and 8 episodes of polymicrobial bacteremia, whereas in the control group there were 13 episodes with documentation of a single Gram-negative, 18 episodes of a single Gram-positive isolate, and 5 episodes of polymicrobial bacteremia (Table 1). Table 2 shows the species distribution of bloodstream isolates in both groups. The most frequent Gram-negative bacteria were E. coli and P. aeruginosa.
Table 3 shows the resistance rates (per 1,000 patients.day) in the two periods. The rate of quinolone-resistant bacteremia (both Gram-positive and Gram-negative) was significantly higher in patients receiving quinolone prophylaxis (6.77 vs. 3.02 per 1,000 patients.day, p = 0.03). In addition, quinolone-resistant enterobacteria were more frequently isolated in period 2 both in cohort patients and in the hematology unit overall (2.12 vs. 0.38 per 1,000 patients.day, p = 0.06 in cohort patients, and 2.54 vs. 0.53 per 1,000 patients.day in the hematology unit, p = 0.004), but remained stable in the hospital (0.76 in period 1 and 0.64 in period 2, p = 0.15). The rates of ESBL production among enterobacteria increased slightly both in cohort patients (0.38 in period vs.1.27 in period 2, p = 0.26) and in the hematology unit (0.52 in period 1 vs. 1.59 in period 2, p = 0.08), and remained stable in the hospital (0.56 in period 1 vs. 0.53 in period 2, p = 0.74). No changes in quinolone resistance among staphylococci were observed in cohort patients.
The genotypic analysis of the isolates from the cohort patients showed a great genetic diversity among isolates recovered from episodes of the cohort, with no similarity between isolates (Figure 1).
(Enlarge Image)
Figure 1.
Molecular analysis of Escherichia coli isolates from cohort patients. A. ERIC2-PCR profiles of Escherichia coli isolates. Lanes 1 and 23: 1 Kb plus molecular size marker; Lanes 2–20: clinical isolates; Lanes 21 and 22: control strains ST69 and ATCC25922. B. Dendrogram of ERIC-2 PCR profiles of Escherichia coli isolates. C: control isolates.