جداول میکروارگانیسم های بیماریزای اولویت دار و آنتی بیوتیک های تعیین شده برای آزمایش تعیین حساسیت ضد میکروبی در برنامه مهار مقاومت میکروبی

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جداول میکروارگانیسم های بیماریزای اولویت دار و آنتی بیوتیک های تعیین شده برای آزمایش تعیین حساسیت ضد میکروبی در برنامه مهار مقاومت میکروبی ویرایش دوم بر اساس ed., 2017 CLSI M100 27 th تابستان ۶۹۳۱ تهیه شده توسط کمیته تخصصی میکروب شناسی آزمایشگاه مرجع سالمت وزارت بهداشت درمان و آموزش پزشکی Page 1 of 18

Escherichia coli Zone Diameter Interpretive Criteria (nearest whole mm) PENICILLINS Ampicillin 10 µg 17 14 16 13 CEPHEMS Cefazolin(PARENTERAL) 30 µg 23 20 22 19 Breakpoints when cefazolin is used for therapy of infections other than uncomplicated UTIs due to E.coli, K. pneumoniae & P.mirabilis. Breakpoints are based on a dosage regimen of 2 g every 8 h. Cefazolin(PARENTERAL) (urine) Cefazolin(ORAL) (surrogate test for oral cephalosporins & uncomplicated UTI) (urine) 30 µg 15-14 Breakpoints when cefazolin is used for therapy of uncomplicated UTIs due to E.coli, K pneumoniae & P.mirabilis. Breakpoints are based on a dosage regimen of 1 g every 12 h. 30 µg 15-14 Breakpoints are for cefazolin when cefazolin results are used to predict results for the oral agents cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime, cephalexin, and loracarbef when used for therapy of uncomplicated UTIs due to E. coli, K. pneumoniae, and P. mirabilis. Cefpodoxime, cefdinir, and cefuroxime may be tested individually because some isolates may be susceptible to these agents while testing resistant to cefazolin. Cefepime 30 μg 25 19 24 18 The Breakpoint for susceptible is based on a dosage regimen of 1 g every 12 h. The Breakpoint for SDD is based on dosing regimens that result in higher cefepime exposure, either higher doses or more frequent doses or both, up to approved maximum dosing regimens. SDD:Susceptible-Dose Dependent Cefotaxime 30 μg 26 23 25 22 Breakpoints are based on a dosage regimen of 1 g every 24 h for ceftriaxone and 1 g every 8 h for cefotaxime. Page 2 of 18

Escherichia coli(continued) Ceftriaxone 30 μg 23 20 22 19 Breakpoints are based on a dosage regimen of 1 g every 24 h for ceftriaxone and 1 g every 8 h for cefotaxime. Ceftazidime 30 μg 21 18 20 17 Breakpoints are based on a dosage regimen of 1 g every 8 h. CARBAPENEMS Imipenem or/and Meropenem 10 μg 10 μg 23 23 20 22 20 22 19 19 AMINOGLYCOSIDES Gentamicin 10 μg 15 13-14 12 Amikacin 30 μg 17 15 16 14 FLUOROQUINOLONES Ciprofloxacin 5 μg 21 16 20 15 Breakpoints are based on a dosage regimen of 500 mg every 6 h or 1 g every 8 h. Interpretive criteria are based on a dosage regimen of 1 g every 8 h. FOLATE PATHWAY INHIBITORS Trimethoprim- sulfamethoxazole 1.25/ 23.75 16 11 15 10 μg NITROFURANS Nitrofurantoin 300 μg 17 15 16 14 For testing and reporting urinary tract isolates only. Tests for confirmation of ESBL-producing Escherichia coli Results Ceftazidime-clavulanate Cefotaxime-clavulanate 30/10 μg 30/10 μg A 5mm increase in a zone diameter for either antimicrobial agent tested in combination with clavulanate vs the zone diameter of the agent when tested alone = ESBL (eg, ceftazidime zone = 16; ceftazidime-clavulanate zone = 21). Page 3 of 18

Klebsiella pneumoniae Zone Diameter Interpretive Criteria (nearest whole mm) CEPHEMS Cefazolin(PARENTERAL) 30 µg 23 20 22 19 Breakpoints when cefazolin is used for therapy of infections other than uncomplicated UTIs due to E.coli, K pneumoniae & P.mirabilis. Breakpoints are based on a dosage regimen of 2 g every 8 h. Cefazolin(PARENTERAL) (urine) Cefazolin(ORAL) (surrogate test for oral cephalosporins & uncomplicated UTI) (urine) 30 µg 15-14 Breakpoints when cefazolin is used for therapy of uncomplicated UTIs due to E.coli, K pneumoniae & P.mirabilis. Breakpoints are based on a dosage regimen of 1 g every 12 h. 30 µg 15-14 Breakpoints are for cefazolin when cefazolin results are used to predict results for the oral agents cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime, cephalexin, and loracarbef when used for therapy of uncomplicated UTIs due to E. coli, K. pneumoniae, and P. mirabilis. Cefpodoxime, cefdinir, and cefuroxime may be tested individually because some isolates may be susceptible to these agents while testing resistant to cefazolin. Cefepime 30 μg 25 19 24 18 The Breakpoint for susceptible is based on a dosage regimen of 1 g every 12 h. The Breakpoint for SDD is based on dosing regimens that result in higher cefepime exposure, either higher doses or more frequent doses or both, up to approved maximum dosing regimens. SDD:Susceptible-Dose Dependent Cefotaxime 30 μg 26 23 25 22 Breakpoints are based on a dosage regimen of 1 g every 24 h for ceftriaxone and 1 g every 8 h for cefotaxime. Page 4 of 18

Klebsiella pneumoniae(continued) Ceftriaxone 30 μg 23 20 22 19 Breakpoints are based on a dosage regimen of 1 g every 24 h for ceftriaxone and 1 g every 8 h for cefotaxime. Ceftazidime 30 μg 21 18 20 17 Breakpoints are based on a dosage regimen of 1 g every 8 h. CARBAPENEMS Imipenem or/and Meropenem 10 μg 10 μg 23 23 20 22 20 22 19 19 AMINOGLYCOSIDES Gentamicin 10 μg 15 13-14 12 Amikacin 30 μg 17 15 16 14 FLUOROQUINOLONES Ciprofloxacin 5 μg 21 16 20 15 FOLATE PATHWAY INHIBITORS Trimethoprim- 1.25/ 23.75 16 11 15 10 sulfamethoxazole μg NITROFURANS Nitrofurantoin 300 μg 17 15 16 14 For testing and reporting urinary tract isolates only. Tests for confirmation of ESBL-producing Klebsiella pneumoniae Results Ceftazidime-clavulanate Cefotaxime-clavulanate 30/10 μg 30/10 μg A 5mm increase in a zone diameter for either antimicrobial agent tested in combination with clavulanate vs the zone diameter of the agent when tested alone = ESBL (eg, ceftazidime zone = 16; ceftazidime-clavulanate zone = 21). Page 5 of 18

When fecal isolates of Salmonella are tested, only ampicillin, a fluoroquinolone, and trimethoprimsulfamethoxazole should be reported routinely. In addition, for extraintestinal isolates of Salmonella spp., a third-generation cephalosporin and chloramphenicol should be tested and reported. Salmonella spp. Zone Diameter Interpretive Criteria (nearest whole mm) PENICILLINS Ampicillin 10 µg 17 14 16 13 CEPHEMS Ceftriaxone (For extraintestinai isolate) 30 μg 23 20 22 19 Breakpoints are based on a dosage regimen of 1 g every 24 h for ceftriaxone Ceftazidime (For extraintestinai isolate) FLUOROQUINOLONES Ciprofloxacin 5 μg 31 21-30 20 30 μg 21 18 20 17 Breakpoints are based on a dosage regimen of 1 g every 8 h. FOLATE PATHWAY INHIBITORS Trimethoprim- 1.25/ 23.75 16 11 15 10 sulfamethoxazole μg PHENICOLS Chloramphenicol 30 μg 18 13 17 12 Tests for confirmation of ESBL-producing Salmonella spp. (Optional) Results Ceftazidime-clavulanate Cefotaxime-clavulanate 30/10 μg 30/10 μg A 5mm increase in a zone diameter for either antimicrobial agent tested in combination with clavulanate vs the zone diameter of the agent when tested alone = ESBL (eg, ceftazidime zone = 16; ceftazidime-clavulanate zone = 21). Page 6 of 18

When fecal isolates of Shigella spp. are tested, only ampicillin, a fluoroquinolone, and trimethoprim-sulfamethoxazole should be reported routinely. Shigella spp. Zone Diameter Interpretive Criteria (nearest whole mm) PENICILLINS Ampicillin 10 µg 17 14 16 13 CEPHEMS Ceftriaxone 30 μg 23 20 22 19 (Only for ciprofloxacin resistant strain) Ceftazidime 30 μg 21 18 20 17 (Only for ciprofloxacin resistant strain) FLUOROQUINOLONES Ciprofloxacin 5 μg 21 16 20 15 FOLATE PATHWAY INHIBITORS Trimethoprim- 1.25/ 23.75 sulfamethoxazole μg 16 11 15 10 Tests for confirmation of ESBL-producing Shigella spp. (Optional) Results Ceftazidime-clavulanate Cefotaxime-clavulanate 30/10 μg 30/10 μg A 5mm increase in a zone diameter for either antimicrobial agent tested in combination with clavulanate vs the zone diameter of the agent when tested alone = ESBL (eg, ceftazidime zone = 16; ceftazidime-clavulanate zone = 21). Page 7 of 18

Pseudomonas aeruginosa Zone Diameter Interpretive Criteria (nearest whole mm) β-lactam/β-lactamase INHIBITOR COMBINATIONS Piperacillin-tazobactam 100/10 µg 21 15 20 14 Breakpoints for piperacillin (alone or with tazobactam) are based on a piperacillin dosage regimen of at least 3 g every 6 h. CEPHEMS Cefepime 30 μg 18 15-17 14 Breakpoints are based on a dosage regimen of 1 g every 8 h or 2 g every 12 h. Ceftazidime 30 μg 18 15-17 14 Breakpoints are based on a dosage regimen of 1 g every 6 h or 2 g every 8 h. CARBAPENEMS Imipenem 10 μg 19 16-18 15 Breakpoints for imipenem are based on a dosage regimen of 1 g every 8 h or 500 mg every 6 h. Meropenem 10 μg 19 16-18 15 Breakpoints for meropenem are based on a dosage regimen of 1 g every 8 h. AMINOGLYCOSIDES Gentamicin 10 μg 15 13-14 12 Tobramycin 10 μg 15 13-14 12 Amikacin 30 μg 17 15 16 14 LIPOPEPTID Colistin - - - - Colistin (methanesulfonate) should generally be administered with a loading dose and at the maximum recommended doses, in combination with other agents. MIC Interpretive Criteria (μg/ml) FLUOROQUINOLONES Ciprofloxacin 5 μg 21 16 20 15 2-4 Page 8 of 18

Acinetobacter spp. Zone Diameter Interpretive Criteria (nearest whole mm) β-lactam/β-lactamase INHIBITOR COMBINATIONS Ampicillin-sulbactam 10/10 µg 15 12-14 11 Piperacillin-tazobactam 100/10 µg 21 18 20 17 CEPHEMS Cefepime 30 μg 18 15-17 14 Ceftazidime 30 μg 18 15-17 14 CARBAPENEMS Imipenem 10 μg 22 19-21 18 Breakpoints for imipenem are based on a dosage regimen of 500 mg every 6 h. Meropenem 10 μg 18 15-17 14 Breakpoints for meropenem are based on a dosage regimen of 1 g every 8 h or 500 mg every 6 h. AMINOGLYCOSIDES Gentamicin 10 μg 15 13-14 12 Tobramycin 10 μg 15 13-14 12 Amikacin 30 μg 17 15 16 14 TETRACYCLINES Minocycline 30 μg 16 13 15 12 LIPOPEPTID Colistin - - - - Colistin (methanesulfonate) should generally be administered with a loading dose and at the maximum recommended doses, in combination with other agents. MIC Interpretive Criteria (μg/ml) 2-4 FLUOROQUINOLONES Ciprofloxacin 5 μg 21 16 20 15 Page 9 of 18

Acinetobacter spp. (continued) FOLATE PATHWAY INHIBITORS Trimethoprim- 1.25/ 23.75 sulfamethoxazole μg 16 11 15 10 Page 10 of 18

Staphylococcus aureus Zone Diameter Interpretive Criteria (nearest whole mm) PENICILLINASE-LABILE PENICILLINS Penicillin 10 units 29-28 *Penicillin should be used to test the susceptibility of all staphylococci to all penicillinaselabile penicillins. Penicillinresistant strains of staphylococci produce β-lactamase. Perform test(s) to detect β-lactamase production on staphylococci for which the penicillin MICs are 0.12 μg/ml or zone diameters 29 mm before reporting the isolate as penicillin susceptible. Rare isolates of staphylococci that contain genes for β-lactamase production may appear negative by β-lactamase tests. Consequently, for serious infections requiring penicillin therapy, laboratories should perform MIC tests and β-lactamase testing on all subsequent isolates from the same patient. PCR testing of the isolate for the blaz β- lactamase gene may be considered. See Tables 3E and 3F. *For oxacillin-resistant staphylococci report penicillin as resistant or do not report. Page 11 of 18

Staphylococcus aureus (continued) PENICILLINASE-STABLE PENICILLINS Cefoxitin 30 μg 22-21 Cefoxitin is tested as a surrogate for oxacillin; report oxacillin susceptible or resistant based on the cefoxitin result. Cefoxitin MIC and disk diffusion tests performed on media other than CAMHB or unsupplemented MHA do not reliably detect meca-mediated resistance in isolates of S.aureus that do not grow on these media (eg, small colony variants). Testing for PBP2a using induced growth (ie, growth taken from the zone margin surrounding a cefoxitin disk on either BMHA or a blood agar plate after 24 hours incubation in 5% CO2) or meca should be done. Isolates that test either meca negative or PBP2a negative or cefoxitin susceptible should be reported as oxacillin susceptible. Page 12 of 18

Staphylococcus aureus (continued) GLYCOPEPTIDES Vancomycin - - - - For S. aureus, vancomycinsusceptible isolates may become vancomycin intermediate during the course of prolonged therapy. MIC tests should be performed to determine the susceptibility of all isolates of staphylococci to Teicoplanin (Optional) (Investigation) TETRACYCLINES Doxycycline 30 μg 16 13-15 12 vancomycin. The disk test does not differentiate vancomycinsusceptible isolates of S. aureus from vancomycin-intermediate isolates, nor does the test differentiate among vancomycin susceptible, -intermediate, and -resistant isolates of CoNS, all of which give similar size zones of inhibition. Send any S. aureus for which the vancomycin is 8 μg/ml to a reference laboratory. MIC Interpretive Criteria (μg/ml) 2 4-8 16 - - - - MIC Interpretive Criteria (μg/ml) 8 16 32 MACROLIDES Erythromycin 15 μg 23 14-22 13 Not routinely reported on organisms isolated from the urinary tract. FLUOROQUINOLONES Ciprofloxacin 5 μg 21 16 20 15 Staphylococcus spp. may develop resistance during prolonged therapy with quinolones. Therefore, isolates that are initially susceptible may become resistant within three to four days after initiation of therapy. Testing of repeat isolates may be warranted. Page 13 of 18

Staphylococcus aureus (continued) NITROFURANTOINS Nitrofurantoin 300 μg 17 15-16 14 FOLATE PATHWAY INHIBITORS Trimethoprim- 1.25/ 23.75 16 11-15 10 sulfamethoxazole μg LINCOSAMIDES Clindamycin 2 μg 21 15-20 14 Inducible clindamycin resistance can be detected by disk diffusion using the D-zone test or by broth microdilution.15-μg erythromycin and 2-μg clindamycin disks spaced 15 26 mm apart. ANSAMYCINS Rifampin 5 μg 20 17-19 16 Rifampin should be used but not reported. Page 14 of 18

Enterococcus spp. Zone Diameter Interpretive Criteria (nearest whole mm) PENICILLINS Ampicillin 10 μg 17-16 The results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin. Ampicillin results may be used to predict susceptibility to amoxicillin-clavulanate, ampicillinsulbactam, and piperacillintazobactam among non βlactamase producing enterococci. Ampicillin susceptibility can be used to predict imipenem susceptibility, providing the species is confirmed to be E. faecalis. GLYCOPEPTIDES Vancomycin 30 μg 17 15-16 14 When testing vancomycin against enterococci, plates should be held a full 24 hours for accurate detection of resistance. Zones should be examined using transmitted light; the presence of a haze or any growth within the zone of inhibition indicates resistance. Organisms with intermediate zones should be tested by an MIC method as described in M07-A10. For isolates for which the vancomycin MICs are 8 to 16 μg/ml, perform biochemical tests for identification as listed under the Vancomycin MIC 8 μg/ml test found in Table 3F. FLUOROQUINOLONES Ciprofloxacin 5 μg 21 16 20 15 NITROFURANTOINS Nitrofurantoin 300 μg 17 15-16 14 OXAZOLIDINONES Linezolid 30 μg 23 21-22 20 Page 15 of 18

HIGH-LEVEL AMINOGLYCOSIDES for Enterococcus spp. Zone Diameter Interpretive Criteria (nearest whole mm) S Inconclusive R Gentamicin 120 μg 10 7-9 = 6 Page 16 of 18

For disk diffusion, test a maximum of 9 disks on a 150-mm plate and 4 disks on a 100-mm plate. Streptococcus pneumonia Zone Diameter Interpretive Criteria (nearest whole mm) PENICILLINS Penicillin (nonmeningitis) Penicillin parenteral (nonmeningitis) (optional) Oxacillin 1 μg 20 - - Isolates of pneumococci with oxacillin zone sizes of 20 mm are susceptible (MIC 0.06 μg/ml) to penicillin. Penicillin and cefotaxime, ceftriaxone, or meropenem MICs should be determined for those isolates with oxacillin zone diameters of 19 mm, because zones of 19 mm occur with penicillin-resistant, -intermediate, or certain -susceptible strains. For isolates with oxacillin zones 19 mm, do not report penicillin as resistant without performing a penicillin MIC test. - - - - MIC Interpretive Criteria (μg/ml) 2 4 8 Doses of intravenous penicillin of at least 2 million units every 4 hours in adults with normal renal function (12 million units per day) can be used to treat nonmeningeal pneumococcal infections due to strains with penicillin MICs 2 μg/ml. Strains with an intermediate MIC of 4 μg/ml may require penicillin doses of 18 to 24 million units per day. CEPHEMS Ceftriaxone (nonmeningitis) TETRACYCLINES Doxycycline 30 μg 28 25-27 24 - - - - MIC Interpretive Criteria (μg/ml) 1 2 4 Page 17 of 18

Streptococcus pneumonia(continued) MACROLIDES Erythromycin 15 μg 21 16-20 15 Not routinely reported on organisms isolated from the urinary tract. FLUOROQUINOLONES Levofloxacin 5 μg 17 14-16 13 FOLATE PATHWAY INHIBITORS Trimethoprim- 1.25/ 23.75 19 16-18 15 sulfamethoxazole μg LINCOSAMIDES Clindamycin 2 μg 19 16-18 15 Inducible clindamycin resistance can be detected by disk diffusion using the D-zone test or by broth microdilution.15μg erythromycin and 2μg clindamycin disks spaced 15 26 mm apart. Page 18 of 18