Table 1.
Susceptibility of Klebsiella pneumoniae to all available antibiotics according to the CLSIa and EUCASTb guideline.
| Antibiotics | Clinical breakpoints (μg/mL) | MIC (μg/mL) | Interpretation | Comment: Type of resistance |
|---|---|---|---|---|
| Amikacin | ≤ 16, 32, ≥ 64 | > 16 | Resistant | Pandrug-resistant |
| Cefepime | ≤ 2, 4-8, ≥ 16 | > 16 | Resistant | |
| Cefixime | ≤ 1, 2, ≥ 4 | > 2 | Resistant | |
| Ceftazidime/Avibactam | ≤ 8/4, ≥ 16/4 | > 8/4 | Resistant | |
| Ceftriaxone | ≤ 1, 2, ≥ 4 | > 4 | Resistant | |
| Cefuroxime | ≤ 4, 8-16, ≥ 32 | > 8 | Resistant | |
| Ciprofloxacin | ≤ 1, 2, ≥ 4 | > 1 | Resistant | |
| Colistin | ≤ 2, ≥ 4 | > 2 | Resistant | |
| Gentamicin | ≤ 4, 8, ≥ 16 | > 4 | Resistant | |
| Imipenem | ≤ 1, 2, ≥ 4 | > 4 | Resistant | |
| Levofloxacin | ≤ 2, 4, ≥ 8 | > 2 | Resistant | |
| Meropenem | ≤ 1, 2, ≥ 4 | > 8 | Resistant | |
| Piperacillin/Tazobactam | ≤ 16/4, ≥ 28/4 | > 64/4 | Resistant | |
| Polymyxin B | ≤ 2, ≥ 4 | > 2 | Resistant | |
| Tigecycline | ≤ 1, 2, ≥ 2 | > 2 | Resistant |
Table 2.
Baseline demographic information, comorbidity and laboratory findings in patients.
| Variable | PMB group (N=106) | CLN group (N=116) | P value |
|---|---|---|---|
| Male/female, n (%) | 78/28 (74/26) | 62/54 (53/47) | |
| Age (year), median (IQR) | 56 (44.5-68) | 55 (46-65) | 0.091 |
| Fever (°F), median (IQR) | 100.5 (100-101) | 101 (100-101) | 0.559 |
| Diabetes, n (%) | 89 (83.95) | 97 (83.62) | 0.022 |
| Hypertension, n (%) | 72 (67.93) | 80 (68.96) | 0.421 |
| CVD, n (%) | 61 (57.52) | 53 (45.68) | 0.542 |
| Bronchial asthma, n (%) | 27 (25.51) | 30 (25.86) | 0.031 |
| CKD, n (%) | 25 (23.63) | 31 (26.72) | 0.011 |
| COPD, n (%) | 25 (23.6) | 27 (23.27) | 0.058 |
| Obesity, n (%) | 22 (20.82) | 18 (15.51) | 0.316 |
| PUD, n (%) | 19 (17.94) | 8 (6.89) | 0.644 |
| CLD, n (%) | 9 (8.55) | 12 (10.34) | 0.021 |
| PD, n (%) | 4 (3.86) | 9 (7.75) | 0.465 |
| SpO2 (%), median (IQR) | 96 (93-98) | 96 (94-98) | 0.249 |
| FiO2, median (IQR) | 50 (40-65) | 45 (40-65) | 0.939 |
| Respiratory rate, (breaths/min), median (IQR) | 19 (16-24) | 21 (18.29-24.7) | 0.487 |
| Heart rate (beat/min), median (IQR) | 87 (83-97.37) | 85 (78-90) | 0.487 |
| PaO2/FiO2 (mmHg) , median (IQR) | 240 (193-255) | 243 (206.72-256) | 0.517 |
| CRP (mg/L), median (IQR) | 158 (136-268.3) | 152.5 (125-243.81) | 0.282 |
| Procalcitonin (ng/mL), median (IQR) | 5 (3.35-8) | 6 (4.81-9) | 0.114 |
| WBC (K/μL), median (IQR) | 18 (16.52-21) | 16.46 (13.2-24) | 0.001 |
| Neutrophils (%), median (IQR) | 65 (55.77-75) | 75 (65-85) | 0.454 |
| Platelet (K/μL), median (IQR) | 186 (151-263) | 162 (125-242.5) | 0.132 |
| D-dimer (mg /L FEU), median (IQR) | 0.96 (0.36-1.74) | 0.57 (0.35-1.4) | 0.005 |
| LDH ((U/L), median (IQR) | 419 (314-522) | 425 (356.5-500.25) | 0.117 |
| Serum creatinine (mg/dL), median (IQR) | 0.9 (0.7-1.2) | 1 (0.8-1.6) | 0.097 |
| ALT (U/L), median (IQR) | 56 (45-76) | 57 (45-75) | 0.597 |
| AST (U/L), median (IQR) | 48 (39-58) | 46 (34-59) | 0.813 |
| Bilirubin (mg/dL), median (IQR) | 0.8 (0.47-0.9) | 0.8 (0.6-0.92) | 0.737 |
| MEWS, median (IQR) | 4 (3-4) | 4 (3-4) | 0.032 |
| APACHE II (score range: 0-71) , median (IQR) | 20 (20-24) | 20 (18-24) | 0.171 |
[i] IQR = interquartile range; n = number; % = percentage; °F = grade Fahrenheit; CVD = cardiovascular disease; CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease; PUD = peptic ulcer disease; CLD = chronic liver disease; PD = parkinson’s disease; SpO2 = oxygen saturation in blood; ; FiO2 = fraction of inspired oxygen; min = minute; PaO2/FiO2 = ratio of arterial oxygen partial pressure to fractional inspired oxygen; CRP = C-reactive protein; mg = milligram; L = liter; FEU = fibrinogen equivalent units; ng = nanogram; WBC = white blood cells; K/μL = thousand cells per micro liter; IL = interleukin; pg/mL = picograms per milliliter; LDH = lactate dehydrogenase; U/L = units per liter; dL = deciliter; ALT = alanine aminotransferase; AST = aspartate aminotransferase; MEWS = Modified Early Warning Score; APACHE II = Acute Physiology and Chronic Health Evaluation.
Table 3.
Clinical outcomes in patients treated with intravenous and aerosolized polymyxin B or colistin
| Parameters | PMB group (N=106) | CLN group (N=116) | P value |
|---|---|---|---|
| Microbial eradication, n (%) | 88 (83) | 79 (68.1) | 0.001 |
| 21-day secondary bacterial infection, n (%) | 24 (22.64) | 28 (27.58) | 0.013 |
| Length-of-intubation (day), median (IQR) | 10 (9-12.25) | 14 (11-19) | 0.001 |
| Length-of-ICU stay (day), median (IQR) | 12 (10-14) | 15 (9-18.5) | 0.072 |
| Adverse drug event, n (%) | |||
| Bronchospasm | 39 (36.79) | 8 (6.89) | 0.001 |
| Nephrotoxicity | 12 (11.32) | 33 (28.44) | 0.002 |
Fig. 1.
Kaplan-Meier survival curve for PMB group (aerosolized plus intravenous polymyxin B) (blue line) and CLN group (aerosolized plus intravenous colistin) (green line). Analysis run using Group (PMB vs CLN) as factor; death as event and time to death as time variable. Multivariate Hazard Ratio (H.R. for death: 0.035; 95% CI=0.007-0.168, P<0.001) is adjusted for baseline characteristics.
Table 4.
Results from the Cox Proportional Hazard model. GROUP=main variable (polymyxin B versus colistin).
| Variable | HR | 95% CI | P value | |
|---|---|---|---|---|
| Lower | Upper | |||
| Group | 0.035 | 0.007 | 0.168 | <0.001 |
| Age | 1.028 | 1.001 | 1.055 | 0.045 |
| PaO2/FiO2 ratio | 1.005 | 0.994 | 1.015 | 0.379 |
| APACHE II | 0.958 | 0.862 | 1.063 | 0.415 |
| Microbial non-eradication | 1.148 | 0.484 | 2.721 | 0.038 |
| Length of intubation | 0.965 | 0.882 | 1.057 | 0.044 |
| Length of ICU stay | 1.043 | 0.99 | 1.099 | 0.117 |