Table 1. Susceptibility of K. pneumoniae to Antimicrobial Agents.
|
Antibiotic |
MIC50 (mg/L) |
MIC90 (mg/L) |
Range (mg/L) |
|
Penicillins Ticarcillin Piperacillin |
256 4 |
>512 >256 |
NS 0.5 - >12 |
|
Penicillins plus beta-lactamase inhibitors Amoxicillin-Clavulanate Ticarcillin-Clavulanate Ampicillin-Sulbactam Piperacillin-Tazobactam |
1 2 4 4 |
2 32 16 16 |
0.25 - 8 1 - 256 2 - >16 1 - 512 |
|
First generation cephalosporins Cefazolin Cephalexin Cefadroxil Cephradine |
2 16 8 8 |
4 32 16 64 |
1- 128 8 - 64 4 - 32 4 - 128 |
|
Second generation cephalosporins Cefamandole Cefprozil Cefaclor Loracarbef Cefuroxime Cefoxitin Cefotetan Cefmetazole |
2 1 1 0.5 2 2 0.25 1 |
2 8 4 1 16 8 0.5 2 |
2 - >32 0.5 - 128 0.5 - 64 0.12 - 32 1 - 32 1 - 16 0.12 - >32 0.5 - 16 |
|
Third generation cephalosporins Cefotaxime Ceftriaxone Cefixime Cefpodoxime Ceftazidime Cefpirome |
0.12 0.12 0.03 0.12 0.12 0.12 0.06 |
0.25 0.25 0.25 0.5 0.25 0.25 1 |
0.016 - >128 0.016 - >128 0.016 - 0.5 0.12 - 32 0.03 - >128 0.03 - >128 0.06 - 1 |
|
Other beta-lactams Ertapenem Imipenem Meropenem Aztreonam |
0.06 0.12 < 0.06 0.5 |
0.5 0.5 0.06 0.5 |
< 0.06 - 16 < 0.06 - 8 < 0.06 - 8 0.5 - >32 |
Table 1a. Susceptibility of K. pneumoniae to Antimicrobial Agents (continued)
|
Antibiotic |
MIC50 (mg/L) |
MIC90 (mg/L) |
Range (mg/L) |
|
|
|
|
|
|
Aminoglycosides Gentamicin Tobramycin Amikacin Netilmicin Streptomycin |
0.25 0.25 0.25 0.12 0.5 |
2 2 2 0.12 15.6 |
0.06 > 128 0.06 > 128 0.06 - 32 0.12 - 2 0.12 - .500 |
|
Quinolones Ciprofloxacin Clinafloxacin Enoxacin Gatifloxacin Gemifloxacin Levofloxacin Moxifloxacin Norfloxacin Ofloxacin Sparfloxacin Trovafloxacin BMS-284756 |
0.03 0.015 0.12 0.06 0.06 0.06 0.12 0.12 0.12 0.06 <0.03 0.12 |
0.25 0.03 0.25 0.25 1 0.12 1 0.25 0.12 0.12 0.5 2 |
0.016 - 16 0.008 - 0.03 0.06 - 2 0.03 - 2 0.03 - 2 0.016 - 2 0.03 - 2 0.06 - 2 0.03 - >32 0.016 - 1 <0.03 - >16 0.03 - >16 |
|
Other antibiotics Azithromycin Colistin Rifampin Chloramphenicol Trimethoprim (TMP) Sulfamethoxazole (SMX) TMP/SMX Nalidixic acid Tetracycline Tigecycline |
8 1 32 4 0.5 16 0.01/0.25 8 0.12 0.5 |
16 8 NS 8 8 NS 1.56/3.12 16 2 0.5 |
NS 0.5-16 NS 0.12-500 0.005 - >25 NS <0.01/0.25- 25/500 4 -64 0.12 - 500 0.125 - 16 |
NS = Not specified
Collated from the references 21, 26, 29, 30, 47, 91, 92, 99, 123, 143, 171, 235, 275
Table 2. Susceptibility of ESBL Producing K. pneumoniae to Antimicrobial Agents.
|
Antibiotic |
MIC50 (mg/L) |
MIC90 (mg/L) |
Range (mg/L) |
|
Penicillins Ticarcillin Piperacillin |
16384 256 |
32768 512 |
NS 16 – 256 |
|
Penicillins plus beta-lactamase inhibitors Amoxicillin - Clavulanate Ticarcillin - Clavulanate Ampicillin - Sulbactam Piperacillin - Tazobactam Cefotaxime - Clavulanate Ceftazidime - Clavulanate Cefotaxime - Sulbactam |
8 64 16 4 0.5 0.5 8 |
16 64 128 32 2 1 32 |
0.25-16 16 - >64 8 - >128 0.5 - >128 0.25 - 2 0.06 - 2 0.25 – 32 |
|
First generation cephalosporins Cefazolin |
128 |
512 |
16 – 512 |
|
Second generation cephalosporins Cefamandole Cefoxitin Cefotetan |
256 16 0.5 |
512 32 2 |
16 - 512 4 - 64 0.03 – 64 |
|
Third generation cephalosporins Cefotaxime Ceftriaxone Ceftazidime Cefepime Cefpirome |
32 32 256 8 16 |
64 64 512 >128 64 |
0.03 - 256 4 - 64 0.25 - 512 0.25 - >128 0.25 – 128 |
Table 2a. Susceptibility of ESBL Producing K. pneumoniae to Antimicrobial Agents (continued)
|
Antibiotic |
MIC50 (mg/L) |
MIC90 (mg/L) |
Range (mg/L) |
|
Other beta lactams Ertapenem Imipenem Meropenem Aztreonam |
0.06 0.5 0.03 32 |
0.5 1 0.03 128 |
0.03 - 16 0.03 - 2 0.03 - 0.12 0.25 - 512 |
|
Aminoglycosides Gentamicin Amikacin |
8 4 |
>16 16 |
0.05 - >16 NS |
|
Quinolones Ciprofloxacin |
0.12 |
4 |
0.12 - >8 |
|
Others Trimethoprim (TMP) Sulfamethoxazole |
>4 76 |
>4 76 |
1 - >4 38-76 |
NS = Not specified
Collated from references 122, 123, 139, 158, 196
Table 3: Mechanisms of Resistance of Klebsiella Pneumoniae to Commonly Used Antibiotics
|
Antibiotic |
Common mechanisms of resistance |
|
Penicillins |
SHV-1 beta-lactamase |
|
Penicillins plus beta-lactamase inhibitor |
Hyperproduction of SHV-1 or TEM-1 beta-lactamase Outer membrane protein loss Inhibitor resistant mutant (IRT) beta-lactamase Some extended-spectrum beta-lactamases Plasmid-mediate AmpC beta-lactamases |
|
Cephamycins |
Outer membrane protein loss Plasmid-mediated AmpC beta-lactamases |
|
Third generation cephalosporins |
Extended-spectrum beta-lactamases Plasmid-mediated AmpC beta-lactamases Hyperproduction of SHV-1 plus outer membrane protein loss |
|
Cefepime |
Extended-spectrum beta-lactamases Plasmid-mediated AmpC beta-lactamases Outer membrane protein loss |
|
Carbapenems |
Outer membrane protein loss plus extended-spectrum beta-lactamase or plasmid-mediated AmpC beta-lactamase Production of a carbapenemase |
|
Aminoglycosides |
Aminoglycosides modifying enzymes |
|
Quinolones |
Mutations in the chromosomal gyrA and parC genes Active efflux/outer membrane protein loss |
Table 4: Treatment and Clinical Outcome of Patients with Serious Infections Due to K. Ozaenae
|
Author |
Site |
Antibiotic |
Outcome |
|
Murray (178) |
Blood, CSF |
Gentamicin, Carbenicillin, Ampicillin |
Died |
|
Murray (178 |
Blood |
Ampicillin, Gentamicin, Doxycycline |
Survived |
|
Chowdhury (64) |
Blood, Liver |
Ampicillin-Sulbactam |
Survived |
|
Strampfer (246) |
Brain |
Chloramphenicol, Ceftazidime, Ampicillin |
Died |
|
Janda (121) |
Cornea |
Carbenicillin, Tobramycin (top) |
Abscess healed |
|
Tang (253) |
CSF |
Cefotaxime |
Survived |
Table 5: Empiric Antibiotic Therapy for Serious Infections Caused by Non-ESBL Producing K. pneumoniae Pending Knowledge of In Vitro Susceptibilities
|
Disease |
First-line therapy |
Alternative if previous anaphylactic reaction to cephalosporins or penicillin |
|
Bacteremia |
Cefotaxime |
Ciprofloxacin |
|
Pneumonia |
Cefotaxime |
Ciprofloxacin |
|
Urinary tract infection |
Ciprofloxacin |
Ciprofloxacin |
|
Meningitis |
Ceftriaxone |
Trimethoprim-sulfamethoxazole |
|
Endocarditis + Gentamicin |
Ceftriaxone + Gentamicin |
Ciprofloxacin |
|
Endophthalmitis + intravitreal amikacin |
Ceftazidime + intravitreal amikacin |
Ciprofloxacin |
|
Liver abscess |
Ceftriaxone |
Ciprofloxacin |
Table 6: Treatment Options for ESBL Producing K. pneumoniae Infections
|
Infection |
First-line |
Alternative if allergic to penicillin |
|
Bacteremia |
Carbapenem |
Quinolone |
|
Ventilator-associated pneumonia |
Carbapenem |
Quinolone |
|
Intra-abdominal abscess |
Carbapenem |
Quinolone |
|
Urinary tract infection |
Quinolone or amoxicillin/clavulanate |
Quinolone |
|
Meningitis |
Meropenem |
Quinolone +/- intraventricular polymyxin B |