During the study period, 201 patients with K. pneumoniae bacteremia were enrolled based on the patient selection criteria (Fig. 1). The patient demographic data were presented in Table 1. The age of patients ranged from 21 to 100 years, with a median age of 69. The majority of patients were male (n = 124, 61.69%). The most prevalent comorbidities included diabetes mellitus (n = 77, 38.31%), impaired liver function (n = 61, 30.35%), and impaired renal function (n = 41, 20.40%). The primary cause of bacteremia was intra-abdominal infection (n = 65, 32.34%), followed by primary bacteremia (n = 64, 31.84%), respiratory tract infection (n = 33, 16.42%), and urinary tract infections (n = 28, 13.93%). Antimicrobial susceptibility results for K. pneumoniae are detailed in Table 2.
Table 1
Demographic and clinical characteristics of patients with Klebsiella pneumoniae bacteremia receiving cefoperazone/sulbactam treatment.*
| All | Agar dilution (1:1) MIC | p value |
MIC ≤ 16 | MIC > 16 |
Number | 201 | 180 | 21 | |
Sex | | | | 0.99 |
Male | 124 (61.69) | 111 (61.67) | 13 (61.90) | |
Female | 77 (38.31) | 69 (38.33) | 8 (38.10) | |
Age (median, range) | 69, 21–100 | 70.78, 22–102 | 74.48, 58–86 | 0.06 |
APACHE II score (Mean ± SD) | 13.98 ± 6.94 | 13.42 ± 6.88 | 18.76 ± 5.80 | 0.001 |
Charlson Comorbidity score > 3 | 156 (77.61) | 137 (76.11) | 19 (90.48) | 0.17 |
Comorbidities | | | | |
Liver function impairment | 61 (30.35) | 56 (31.11) | 5 (23.81) | 0.62 |
Renal function impairment | 41 (20.40) | 31 (17.22) | 10 (47.62) | 0.003 |
Heart failure | 15 (7.46) | 15 (8.33) | 0 (0.00) | 0.38 |
Diabetes mellitus | 77 (38.31) | 65 (36.11) | 12 (57.14) | 0.10 |
Neutropenia | 8 (3.98) | 8 (4.44) | 0 (0.00) | 0.99 |
Immunosuppressant therapy | 14 (6.97) | 10 (5.56) | 4 (19.05) | 0.04 |
Metastatic tumor | 35 (17.41) | 33 (18.33) | 2 (9.52) | 0.54 |
Infection sources | | | | 0.48 |
Respiratory tract | 33 (16.42) | 27 (15.00) | 6 (28.57) | |
Urinary tract | 28 (13.93) | 25 (13.89) | 3 (14.29) | |
Intra-abdomen | 65 (32.34) | 60 (33.33) | 5 (23.81) | |
Primary bacteremia | 64 (31.84) | 57 (31.67) | 7 (33.33) | |
Others | 11 (5.47) | 11 (6.11) | 0 (0.00) | |
Outcomes | | | | 0.001 |
Favorable | 156 (77.61) | 146 (81.11) | 10 (47.62) | |
Cure | 62 (30.84) | 59 (32.78) | 3 (14.29) | |
Improvement | 94 (46.77) | 87 (48.33) | 7 (33.33) | |
Unfavorable | 45 (22.39) | 34 (18.89) | 11 (52.38) | |
Lack of efficacy | 21 (10.45) | 16 (8.89) | 5 (23.81) | |
Death | 24 (11.94) | 18 (10.00) | 6 (28.57) | |
MIC, mimimal inhibitory concentration. |
*Data are n (%) unless otherwise stated. |
Table 2
The antimicrobial susceptibilities of 201 Klebsiella pneumoniae isolates.
Antimicrobial agents | Susceptibility (n/N) % |
S | I | R |
Amikacin | 95.02 | 1.49 | 3.48 |
Gentamicin | 76.12 | 5.97 | 17.91 |
Ampicillin | 0.00 | 0.00 | 100.00 |
Piperacillin/Tazobactam | 74.63 | 7.46 | 17.91 |
Cefazolin | 34.33 | 27.36 | 38.31 |
Ceftriaxone | 68.66 | 0.99 | 30.35 |
Ceftazidime | 65.67 | 4.48 | 29.85 |
Cefepime | 83.08 | 1.00 | 15.92 |
Ciprofloxacin | 67.66 | 6.47 | 25.87 |
Levofloxacin | 73.13 | 3.48 | 23.38 |
Imipenem | 90.05 | 1.99 | 7.96 |
Ertapenem | 90.05 | 2.99 | 6.96 |
Tigecycline | 89.55 | 5.97 | 4.48 |
Trimethoprim/sulfamethoxazole | 58.71 | 0.00 | 41.29 |
The MIC of CPZ alone and the 1:1 combination of CPZ/SUL against K. pneumoniae are shown in Table 3. The MIC ranges and MIC50 values for CPZ and CPZ/SUL were similar. However, the MIC90 values were lower for CPZ/SUL than for CPZ alone. Among the 201 isolates, 180 (89.55%) were susceptible, six (2.99%) were intermediate, and 15 (7.46%) were resistant to CPZ/SUL. K. pneumoniae isolates were more susceptible to CPZ/SUL than to CPZ. For isolates that were not susceptible to CPZ, the addition of SUL restored the susceptibility rate from 0 to 53.33% and reduced the resistance rate from 82.22–33.33% (Table 3). Distribution of the cefoperazone/sulbactam MIC values among those K. pneumoniae isolates were showed in Fig. 2. Most of those K. pneumoniae isolates in this study exhibited MIC values of less than 8 µg/ml (Fig. 2).
Table 3
The minimal inhibitory concentrations and the susceptibilities of cefoperazone alone and in combination with sulbactam (1:1) against Klebsiella pneumoniae isolates.
K. pneumoniae (n = 201) | MIC (ug/ml) | | Susceptibility [%(n)]a |
MIC50 | MIC90 | MIC range | | S | I | R |
CPZ | 0.25 | > 64 | 0.0625 ~ > 64 | | 77.61% (156) | 3.98% (8) | 18.41% (37) |
CPZ/SUL | 0.25 | 32 | 0.0625 ~ > 64 | | 89.55% (180) | 2.99% (6) | 7.46% (15) |
CPZnS K. pneumoniae (n = 45) | MIC (ug/ml) | | Susceptibility [%(n)]a |
MIC50 | MIC90 | MIC range | | S | I | R |
CPZ | > 64 | > 64 | 32 ~ > 64 | | 0.00% (0) | 17.78% (8) | 82.22% (37) |
CPZ/SUL | 16 | > 64 | 2 ~ > 64 | | 53.33% (24) | 13.33% (6) | 33.33% (15) |
aThe susceptibility breakpoints were adapted from Clinical and Laboratory Standards Institute 2019 for cefoperzaone against Enterobacterales: S, MIC ≤ 16 mg/L; I, MIC = 32 mg/L; R, MIC ≥ 64 mg |
CPZnS, cefoperazone-non-susceptible; CPZ, cefoperazone; SUL, sulbactam; CPZ/SUL, cefoperazone/sulbactam; MIC, minimal inhibitory concentration. |
Outcome evaluations revealed that 156 patients (77.61%) exhibited favorable outcomes (cure and improvement) and 45 patients (22.39%) showed unfavorable outcomes. Unfavorable outcomes included death (n = 24, 11.94%) and lack of treatment efficacy (n = 21, 10.45%) (Table 1). The clinical outcomes correlated with CPZ/SUL MIC values were showed in Fig. 3. As the MIC value increased, the rate of favorable outcomes decreased, and the 30-days mortality rate increased.
Comparing the patient characteristics and outcomes in causative K. pneumoniae isolates with CPZ/SUL MIC ≤ 16 µg/ml (n = 180) and > 16 µg/ml (n = 21) in Table 1, we observed that unfavorable outcomes were more frequent in those with MIC > 16 µg/ml than those with MIC ≤ 16 µg/ml (n = 34, 18.89% vs. n = 11, 52.38%, p = 0.001). Those infected by isolates with MIC > 16 µg/ml had a higher APACHE II scores (13.42 ± 6.88 vs. 18.76 ± 5.80 points, p = 0.001) and higher prevalence of impaired renal function (n = 31, 17.22% vs. n = 10, 47.62%, p = 0.003). There were no significant differences in sex, age, or source of infection between the two groups.
Logistic regression analysis of the prognostic factors for unfavorable outcomes was shown in Table 4. Comparing the two groups, patients with higher APACHE II score (mean ± standard deviation, 12.74 ± 6.35 vs. 18.27 ± 7.18 points; p < 0.001), metastatic tumors (n = 19, 12.18% vs. n = 16, 35.56%; p < 0.001), and infection by K. pneumoniae isolates with CPZ/SUL MIC > 16 µg/ml (n = 10, 6.41% vs. n = 11, 24.44%; p = 0.001) were associated with a higher risk of unfavorable outcomes in univariate analysis. In multivariate analysis, patients with a higher APACHE II score (OR, 1.14; 95% CI, 1.07–1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31–14.40; p < 0.001), and infection by K. pneumoniae isolates with CPZ/SUL MIC > 16 µg/ml (OR, 4.30; CI, 1.50–12.27; p = 0.006) were independently associated with unfavorable outcomes.
Table 4
Logistic regression analyses of prognostic factors associated with unfavorable outcomes in patients with Klebsiella pneumoniae bacteremia.*
| Univariant analysis | | Multivariant analysis |
| Favorable outcomes | Unfavorable outcomes | p value | | OR (95%CI) | p value |
Number | 156 | 45 | | | | |
Sex | | | 0.93 | | 0.97 (0.43–2.16) | 0.93 |
Male | 96 (61.54) | 28 (62.22) | | | | |
Female (n, %) | 60 (38.46) | 17 (37.78) | | | | |
Age (median, range) | 68, 21–100 | 71, 32–98 | 0.64 | | 0.99 (0.96–1.02) | 0.32 |
APACHE II score (Mean ± SD) | 12.74 ± 6.35 | 18.27 ± 7.18 | < 0.001 | | 1.14 (1.07–1.21) | < 0.001 |
Charlson Comorbidities score > 3 | 117 (75.00) | 39 (86.67) | 0.10 | | | |
Co-morbidities | | | | | | |
Liver function impairment | 45 (28.85) | 16 (35.56) | 0.39 | | | |
Renal function impairment | 33 (21.15) | 8 (17.78) | 0.62 | | | |
Heart failure | 12 (7.69) | 3 (6.67) | 0.82 | | | |
Diabetes mellitus | 55 (35.26) | 22 (48.89) | 0.10 | | | |
Neutropenia | 7 (4.49) | 1 (2.22) | 0.50 | | | |
Immunosuppressant therapy | 12 (7.69) | 2 (4.44) | 0.46 | | | |
Metastatic tumor | 19 (12.18) | 16 (35.56) | < 0.001 | | 5.76 (2.31–14.40) | < 0.001 |
Infection sources | | | 0.10 | | | |
Respiratory tract | 18 (11.54) | 15 (33.33) | | | | |
Urinary tract | 23 (14.74) | 5 (11.11) | | | | |
Intra-abdomen | 58 (37.18) | 7 (15.56) | | | | |
Primary bacteremia | 50 (32.05) | 14 (31.11) | | | | |
Others | 7 (4.49) | 4 (8.89) | | | | |
MIC > 16 ug/ml | 10 (6.41) | 11 (24.44) | 0.001 | | 4.30 (1.50-12.27) | 0.006 |
*Data are n (%) unless otherwise stated. |
MIC, minimal inhibitory concentration. |