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Inpatient care of community-acquired pneumonia: RESULTS (2)

Analysis by empirical antibiotic regimen

The most commonly-selected antibiotic regimens are shown in Figure 2. Quinolone monotherapy (levofloxacin in 98%) and cephalosporin monotherapy (cefuroxime in over 90%) were the two most common regimens in the recent and early cohorts, respectively. Baseline clinical characteristics and univariate outcome analyses classified by empirical antibiotics are presented in Tables 3 and 4. On average, patients receiving empirical cephalosporin plus a macrolide or anaerobic coverage had higher PSI scores, while patients treated with empirical macrolide monotherapy had lower PSI scores (Table 3). Univariate analyses of clinical outcomes were consistent with the differences in PSI scores. Patients receiving empirical cephalosporin plus a macrolide or anaerobic coverage had longer LOSs and higher mortality, while patients treated with empirical macrolide monotherapy had shorter LOSs and lower mortality (Table 4).

To assess the specific impact of different empirical antibiotic regimens, multivariable modelling of mortality, LOS, duration of IV therapy and antibiotic cost was performed (Table 5). Despite controlling for PSI, time to initial antibiotic dose and study site, patients receiving empirical cephalosporin plus a macrolide or coverage for anaerobes had significantly higher mortality. Both of these groups also had higher antibiotic costs. Patients treated with empirical macrolide monotherapy had a shorter LOS and duration of IV therapy, as well as lower antibiotic cost. Patients treated with quinolone monotherapy had a shorter duration of IV antibiotic therapy and lower antibiotic costs. Toxicities necessitating a change in therapy were uncommon. This occurred in two patients treated with levofloxacin and three patients treated with cephalosporin-based regimens.

Figure 2) Initial empirical antibiotics for all cases expressed
Figure 2) Initial empirical antibiotics for all cases expressed as the per cent of all patients receiving each empiric antibiotic regimen. Quinolone is quinolone monotherapy (levofloxacin in 98%); Ceph is cephalosporin monotherapy (second-generation cephalosporin [cefurox-ime] in over 90%o); Ceph + macrolide is cephalosporin plus macrolide therapy; Anaerobic is regimens that included agents with significant anaerobic activity; Macrolide is macrolide monotherapy

Table 3. Treatment and outcomes classified by empirical antibiotic therapy

Empirical antibiotic regimen
Characteristic Quinolonemonotherapy*(n=254) Cephalosporinmonotherapy”*(n=229) Cephalosporin plus macrolide (n=96) Macrolidemonotherapy(n=26) Anaerobicregiment(n=58)
Age in years (median [quartiles]) 77 78 80 64 82 <0.0001
Female sex (n [%]) 100 77 38 11 28 0.3
Long-term care residence (n [%]) 56 41 21 (22) 2 (8) 30 <0.0001
PSI score (mean ± SD)PSI class distribtuon (n [%]) 115±35 116±35 123±39 82±35 125±38 <0.0001
1-3 60 61 18 16 13 <0.0001
4 115 103 36 7 21
5 78 65 42 3 24
Time to first antibiotic dose (h) (median [quartiles]) 4 6 4 6 4 0.005

*Levofloxacin in 98% of cases; fSecond-generation cephalosporin (cefuroxime) in over 90% of cases; *Regimens that included agents with significant activity against anaerobic organisms; §Comparison across all groups. PSI Pneumonia severity index

Table 4. Baseline clinical characteristics classified by empirical antibiotic therapy

Characteristic Empirical antibiotic regimen
Quinolonemonotherapy*(n=254) Cephalosporinmonotherapy*(n=229) Cephalosporin plus macrolide (n=96) Macrolidemonotherapy(n=26) Anaerobicregiment(n=58)
Duration of intravenous therapy in days 1 (0, 2) 4 5 1 (0, 2) 5 <0.0001
(median [quartiles])
Antibiotic cost (median [range]) $49.65 $72.12 $156.96 $27.02 $176.56 <0.0001
($24.00 to $79.00) ($43.14 to $104.28) ($98.08 to $256.58) ($13.40 to $46.91) ($98.01 to $288.48)
Length of stay in days (median [quartiles]) 7 7 8 6 9 0.02
Mortality (n [%]) 17 12 17 1 14 <0.0001
Total number antibiotics (n [%])
1 175 159 0 10 0 <0.0001
2 58 50 42 10 21
>3 21 20 54 6 37

*Levofloxacin in 98% of cases; tSecond-generation cephalosporin (cefuroxime) in over 90% of cases; *Regimens that included agents with significant activity against anaerobic organisms; §Comparison across all groups

Table 5. Multivariable analysis classified by empirical antibiotic therapy

Empirical antibiotic regimen
Characteristic Quinolonemonotherapy*(n=254) Cephalosporinmonotherapy!(n=229) Cephalosporin plus macrolide (n=96) Macrolidemonotherapy(n=26) Anaerobicregiment(n=58)
Mortality (odds ratio [95% CI]) NS Reference 2.7 (1.2 to 6.4); P=0.02 NS 2.7 (1.2 to 6.5); P=0.001
Difference in length of stay in days (95% CI) NS Reference NS -2.4 (-0.6 to -3.8); P=0.01 NS
Difference in duration of intravenous therapy in days (95% CI) -2.3 (-2.0 to -2.5); P<0.0001 Reference 1.1 (0.3 to 2.0); P=0.005 -2.6 (-1.9 to -3.1); P<0.0001 NS
Difference in antibiotic cost (95% CI) -$19.19 (-$11.41 to -$25.85); P<0.0001 Reference $91.35 -$43.71 ($61.42 to $128.33); (-$32.58 to -$51.06); P<0.0001 P<0.0001 $64.76 ($34.58 to $104.06); P<0.0001

Outcomes compared with cephalosporin monotherapy cohort as reference group. *Levofloxacin in 98% of cases; fSecond-generation cephalosporin (cefuroxime) in over 90% of cases; *Regimens that included agents with significant activity against anaerobic organisms. NS Not significant