Table 1: Breakpoints Used to Determine Susceptible, Intermediate, and Resistant Categories for H. influenzae
Based on PK/PD, BSAC, and CLSI Interpretative Breakpoints.
|
Antimicrobial |
Breakpoint (µg/ml) based ona |
|||||||
|
PK/PD |
BSAC |
CLSI |
||||||
|
S |
R |
S |
I |
R |
S |
I |
R |
|
|
Parenteral agents |
||||||||
|
Ampicillin |
£2 |
³4 |
£1 |
-- |
³2 |
£1 |
2 |
³4b |
|
Ampicillin-sulbactan |
£2 |
³4 |
-- |
-- |
-- |
£2 |
-- |
³2 |
|
Piperacillin-tazobactan |
£8 |
³16 |
-- |
-- |
-- |
£1 |
-- |
³2 |
|
Cefuroxime sodium |
£4 |
³4 |
³4 |
-- |
³2 |
£4 |
8 |
³16 |
|
Cefotaxime |
£2 |
³4 |
£1 |
-- |
³2 |
£2 |
-- |
-- |
|
Ceftriaxone |
£2 |
³4 |
£1 |
-- |
³2 |
£2 |
-- |
-- |
|
Cefepime |
£4 |
³8 |
-- |
-- |
-- |
£2 |
-- |
-- |
|
Ceftazidime |
£8 |
³16 |
£2 |
-- |
³4 |
£2 |
-- |
-- |
|
Meropenem |
£4 |
³8 |
£4 |
-- |
³8 |
£0.5 |
-- |
-- |
|
Imipenem |
£4 |
³8 |
£4 |
-- |
³8 |
£4 |
-- |
-- |
|
Ertapenem |
£1 |
³2 |
£2 |
-- |
³4 |
£0.5 |
-- |
-- |
|
Parenteral and oral agents |
||||||||
|
Erythromycin |
£0.25 |
³0.5 |
£0,5 |
1-8 |
³16 |
-- |
-- |
-- |
|
Clarithromycin |
£0.25 |
³0.5 |
£0.5 |
1-16 |
³32 |
£8 |
16 |
³32 |
|
Azithromycin |
£0.12 |
³0.25 |
£0.25 |
0.5-4 |
³8 |
£4 |
-- |
-- |
|
Doxycyclin |
£0.25 |
³0.5 |
-- |
-- |
-- |
-- |
-- |
-- |
|
Trimethoprim-sulfamethoxazolee |
£0.5/9.5 |
³1/19 |
£1.6/30.4 |
-- |
³32-60.8 |
£0.5/9.5 |
1/19-2/38 |
³4/76 |
|
Ciprofloxacin |
£1 |
³2 |
£0.5 |
-- |
³1 |
£1 |
-- |
-- |
|
Ofloxacin |
£2 |
³4 |
£0.5 |
-- |
³1 |
£2 |
-- |
-- |
|
Gemifloxacin |
£0.25 |
³0.5 |
£0.25 |
-- |
³0.5 |
-- |
-- |
-- |
|
Levofloxacin |
£2 |
³4 |
£1 |
-- |
³2 |
£2 |
-- |
-- |
|
Gatifloxacin |
£1 |
³2 |
£1 |
-- |
³2 |
£1 |
-- |
-- |
|
Moxifloxacin |
£1 |
³2 |
£0,5 |
-- |
³1 |
£1 |
-- |
-- |
|
Rifampicin |
ND |
ND |
-- |
-- |
-- |
£1 |
2 |
³4 |
|
Chloramphenicol |
£4 |
³8 |
£2 |
-- |
³4 |
£2 |
4 |
³8 |
|
Oral Agents |
||||||||
|
Amoxicillin (1,5g/d; 45 mg/kg/d |
£2 |
³4 |
£1 |
-- |
³2 |
-- |
-- |
-- |
|
Amoxicillin (3-4g/d; 90 mg/kg/d |
£4c |
³8c |
-- |
-- |
-- |
-- |
-- |
-- |
|
Amoxicillin-clavulanate (1,5g-250mg/d; 45-6,4mg/kg/d |
£2c |
³4c |
£1 |
-- |
³2 |
£4 |
-- |
³8d |
|
Amoxicillin-clavulanate (4g-6,4mg/d; 45mg/kg/d |
£4c |
³8c |
-- |
-- |
-- |
-- |
-- |
-- |
|
Cafaclor |
£0.5 |
³1 |
£1 |
-- |
³2 |
£8 |
16 |
³32 |
|
Cefuroxime axetil |
£1 |
³2 |
£1 |
-- |
³2 |
£4 |
8 |
³16 |
|
Cefixime |
£1 |
³2 |
-- |
-- |
-- |
£1 |
-- |
-- |
|
Cefprozil |
£1 |
³2 |
-- |
-- |
-- |
£8 |
16 |
³32 |
|
Cefdinir |
£0.5 |
³1 |
-- |
-- |
-- |
£1 |
-- |
-- |
|
Cefpodoxime |
£0.5 |
³1 |
-- |
-- |
-- |
£2 |
-- |
-- |
|
Telithromycin |
£0.5f |
³1f |
£0.5 |
1-2 |
³4 |
£4 |
8 |
³16 |
|
Tetracycline |
£2g |
³4g |
£1 |
-- |
³2 |
£2 |
4 |
³8 |
aS, susceptible; I, intermediate;; R, resistant; ND, Not defined; --, no breakpoint available
bCLSI breakpoint used to define beta-lactamase negative ampicillin susceptible (BLNAS)
cBreakpoints are expressed as amoxicillin component; testing breakpoints are expressed as amoxicillin component; testing was performed using 2:1 ratio of amoxicillin/clavulanic acid
dBreakpoints used to defined beta-lactamase positive amoxicillin-clavulanate-resistant (BLPACR)
eBreakpoints are expressed as trimethoprim component; testing was performed using a 1:19 ratio of trimethoprim/sulfamethoxqazole.
fLimited information is currently available to determine PK/PD breakpoints
gThe
microbiological breakpoint was used in absence of PK/PD studies
Table 2: Susceptibility of Worldwide Isolates of H. influenzae (n=8,523) to 23 Antimicrobials and MIC50s and MIC90sa
|
Antimicrobial |
MIC50s (µg/ml) |
MIC90sa (µg/ml) |
%S by PK/PD |
CLSI |
|
|
%S |
%R |
||||
|
Ampicillin |
0.25 |
>16 |
NA |
81.9 |
17.0 |
|
Amoxicillin |
0.5 |
>16 |
81.6 |
83.2 |
16.8 |
|
Amoxicillin-clavulanate lower dose |
0.5 |
1 |
98.1 |
99.6 |
0.4 |
|
Amoxicillin-clavulanate higher dose |
0.5 |
1 |
99.6 |
NA |
NA |
|
Cafaclor |
4 |
16 |
1.4 |
89.7 |
3.6 |
|
Cefuroxime axetil |
1 |
2 |
83.6 |
98.1 |
0.7 |
|
Cefixime |
0.03 |
0.06 |
99.8 |
99.8 |
NA |
|
Ceftriaxone |
£0.004 |
0.008 |
100 |
100 |
NA |
|
Cefprozil |
2 |
8 |
22.3 |
92.5 |
2.6 |
|
Cefdinir |
0.25 |
0.5 |
92.0 |
97.6 |
NA |
|
Erythromycin |
4 |
8 |
<0.5 |
NA |
NA |
|
Clarithromycin |
8 |
16 |
<0.” |
79.6 |
0.9 |
|
Azithromycin |
1 |
2 |
<1.2 |
99.5 |
NA |
|
Chloramphenicol |
0.5 |
1 |
98.1 |
97.9 |
1.9 |
|
Doxycycline |
0.5 |
1 |
28.9 |
NA |
NA |
|
Trimethoprim-sulfamethoxazole |
0.12 |
>4 |
78.3 |
78.3 |
17.0 |
|
Ciprofloxacin |
0.015 |
0.03 |
99.9 |
99.9 |
NA |
|
Ofloxacin |
0.03 |
0.06 |
99.9 |
99.9 |
NA |
|
Gemifloxacin |
0.004 |
0.015 |
99.9 |
NA |
NA |
|
Levofloxacin |
0.015 |
0.015 |
99.9 |
99.9 |
NA |
|
Gatifloxacin |
0.008 |
0.015 |
99.9 |
99.9 |
NA |
|
Moxifloxacin |
0.015 |
0.03 |
99.8 |
99.8 |
NA |
AData
are from the Alexander Project 1998 to 2000 (
Table
3: Some Reported Drug Concentrations in Body Compartments
Following Therapeutic
Doses of Antibiotics (ug/ml)
|
Drug |
Cerebrospinal fluid |
Respiratory tract |
Middle ear fluid |
|
Penicillin V |
|
|
6 |
|
Ampicillin |
03 |
025-06 |
02-22 |
|
Amoxicillin |
2 |
09-72 |
18-23 |
|
Clavulanate |
|
1-16 |
|
|
Sulbactam |
42 |
03 |
|
|
Erythromycin |
|
|
06 |
|
Sulfisoxazole |
|
|
37 |
|
Trimethoprim |
|
|
19 |
|
Sulfamethoxazole |
|
|
17 |
|
Chloramphenicol |
57 |
|
|
|
Ciprofloxacin |
035-056 |
|
|
|
Rifampicin |
027 |
|
|
|
Cephradine |
<15 |
13 |
|
|
Cephalexin |
|
03 |
|
|
Cefuroxime |
03-217 |
24 |
|
|
Cefotaxime |
1-15 |
06 |
|
|
Ceftriaxone |
1-135* |
19-27 |
|
|
Ceftazidime |
1-30 |
56-7 |
|
|
Cefpodoxime |
|
11 |
|
|
Cefpriome |
|
72 |
|
|
Cefamandole |
094 |
|
|
|
Cefixime |
02-117 |
<02-24 |
|
|
Azithromycin |
|
9 |
|
|
Clarithromycin |
|
9-17 |
|
|
Aztreonam |
3 |
|
|
|
Imipenem |
21** |
|
|
|
Meropenem |
28 |
|
|
*(up to 58)
**(up to 86 in early phase of acute bacterial meningitis)
Adapted from references:
Table 4: Recommended Drug Dosages for Meningitis [Download PDF]
|
|
Adults - total daily dose (dosing interval; hours) |
Children - mg/kg/day (dosing interval; hours) |
|
Ampicillin |
12 (4) |
200-400 (3-6) |
|
Chloramphenicol |
4 -6 (6) |
75-100 (6-8) |
|
Cefotaxime |
8-12 (6-8) |
200 (6) |
|
Ceftazidime |
6 (8) |
125-200 (6-8) |
|
Ceftriaxone |
4 (12-24) |
100 (12-24) |
|
Meropenem |
|
120 (8) |
|
Rifampicin |
06 (24) |
10-20 (12-24) |
|
Dexamethasone |
|
06 (6) |
Adapted from references:
Table 5: Dosages of Antibiotics Used in H influenzae Pneumonia and Otitis Media [Download PDF]
|
|
Total Daily Dose (mg/kg/day) |
|
|
Drug |
Adults (dosing interval; hours) |
Children (dosing interval; hours) |
|
Ampicillin |
4g (6) |
50-200 (6) |
|
Amoxicillin |
15g (8) |
30-60 (8) |
|
Trimethoprim-sulfamethoxazole |
288g (12) |
8 (12) |
|
Cefaclor |
15g (8) |
40 (8) |
|
Cefuroxime |
500 (12) |
30 (12) |
|
Third-generation cephalosporins |
as for meningitis |
as for meningitis |
|
Cefixime |
200-400 (12-24) |
8 (12-24) |
|
Ceftibuten |
400 (24) |
9 (24) |
|
Cefpodoxime |
200-400 (12) |
8 (12) |
|
Azithromycin |
500 (24) |
200-400mg/day (24) |
|
Clarithromycin |
500 (12) |
15 (12) |
|
Ciprofloxacin |
05-15(12) |
0-20 (12) |