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Enterobacterales
E. coli, Klebsiella, Proteus, Enterobacter, Serratia, Citrobacter — Table 2A-1
| Antibiotic | Disk | Zone Diameter (mm) | MIC (µg/mL) | Notes | ||||
|---|---|---|---|---|---|---|---|---|
| S ≥ | I | R ≤ | S ≤ | I | R ≥ | |||
| Ampicillin | 10 µg | 17 | 14–16 | 13 | 8 | 16 | 32 | Predicts amoxicillin |
| Amoxicillin-clavulanate | 20/10 µg | 18 | 14–17 | 13 | 8/4 | 16/8 | 32/16 | |
| Ampicillin-sulbactam | 10/10 µg | 15 | 12–14 | 11 | 8/4 | 16/8 | 32/16 | |
| Piperacillin-tazobactam | 100/10 µg | 25 | SDD 21–24 | 20 | 8/4 | SDD 16/4 | 32/4 | |
| Cefazolin (systemic) | 30 µg | 23 | 20–22 | 19 | 2 | 4 | 8 | |
| Cefazolin ᵁ | 30 µg | 15 | — | 14 | 16 | — | 32 | Uncomplicated UTI only |
| Cefotaxime | 30 µg | 26 | 23–25 | 22 | 1 | 2 | 4 | |
| Ceftriaxone | 30 µg | 23 | 20–22 | 19 | 1 | 2 | 4 | |
| Cefuroxime (parenteral) | 30 µg | 18 | 15–17 | 14 | 8 | 16 | 32 | |
| Cefepime | 30 µg | 25 | 19–24 | 18 | 2 | 4–8 | 16 | SDD: dose-dependent |
| Ceftazidime | 30 µg | 21 | 18–20 | 17 | 4 | 8 | 16 | |
| Ceftazidime-avibactam | 30/20 µg | 21 | — | 20 | 8/4 | — | 16/4 | KPC/OXA-48 producers |
| Ertapenem | 10 µg | 22 | 19–21 | 18 | 0.5 | 1 | 2 | |
| Imipenem | 10 µg | 23 | 20–22 | 19 | 1 | 2 | 4 | |
| Meropenem | 10 µg | 23 | 20–22 | 19 | 1 | 2 | 4 | |
| Gentamicin | 10 µg | 18 | 15–17 | 14 | 2 | 4 | 8 | |
| Tobramycin | 10 µg | 17 | 13–16 | 12 | 2 | 4 | 8 | |
| Amikacin | 30 µg | 20 | 17–19 | 16 | 4 | 8 | 16 | |
| Ciprofloxacin | 5 µg | 26 | 22–25 | 21 | 0.25 | 0.5 | 1 | |
| Levofloxacin | 5 µg | 21 | 17–20 | 16 | 0.5 | 1 | 2 | |
| Trimethoprim-sulfamethoxazole | 1.25/23.75 µg | 16 | 11–15 | 10 | 2/38 | — | 4/76 | |
| Tetracycline | 30 µg | 15 | 12–14 | 11 | 4 | 8 | 16 | |
| Nitrofurantoin ᵁ | 300 µg | 17 | 15–16 | 14 | 32 | 64 | 128 | Urine only |
| Chloramphenicol | 30 µg | 18 | 13–17 | 12 | 8 | 16 | 32 | |
Salmonella & Shigella spp.
Table 2A-2 — Specific breakpoints differ from other Enterobacterales
| Antibiotic | Disk | Zone Diameter (mm) | MIC (µg/mL) | Notes | ||||
|---|---|---|---|---|---|---|---|---|
| S ≥ | I | R ≤ | S ≤ | I | R ≥ | |||
| Ampicillin | 10 µg | 17 | 14–16 | 13 | 8 | 16 | 32 | |
| Cefotaxime | 30 µg | 26 | 23–25 | 22 | 1 | 2 | 4 | |
| Ceftriaxone | 30 µg | 23 | 20–22 | 19 | 1 | 2 | 4 | |
| Ciprofloxacin (Salmonella) | 5 µg | 31 | 21–30 | 20 | 0.06 | 0.12–0.5 | 1 | ⚠ Stricter cutoff than Enterobacterales |
| Ciprofloxacin (Shigella) | 5 µg | 26 | 22–25 | 21 | 0.25 | 0.5 | 1 | |
| Levofloxacin (Shigella) | 5 µg | 21 | 17–20 | 16 | 0.5 | 1 | 2 | Shigella only |
| Azithromycin (S. Typhi) | 15 µg | 13 | — | 12 | 16 | — | 32 | S. Typhi only |
| Azithromycin (Shigella) | 15 µg | 16 | 11–15 | 10 | 8 | 16 | 32 | Shigella only |
| Trimethoprim-sulfamethoxazole | 1.25/23.75 µg | 16 | 11–15 | 10 | 2/38 | — | 4/76 | |
| Ertapenem | 10 µg | 22 | 19–21 | 18 | 0.5 | 1 | 2 | After resistance to Tier 1 |
| Tetracycline | 30 µg | 15 | 12–14 | 11 | 4 | 8 | 16 | |
Pseudomonas aeruginosa
Table 2B-1
| Antibiotic | Disk | Zone Diameter (mm) | MIC (µg/mL) | Notes | ||||
|---|---|---|---|---|---|---|---|---|
| S ≥ | I | R ≤ | S ≤ | I | R ≥ | |||
| Piperacillin-tazobactam | 100/10 µg | 22 | 18–21 | 17 | 16/4 | 32/4 | 64/4 | |
| Ceftazidime | 30 µg | 18 | 15–17 | 14 | 8 | 16 | 32 | |
| Cefepime | 30 µg | 18 | 15–17 | 14 | 8 | 16 | 32 | |
| Ceftazidime-avibactam | 30/20 µg | 21 | — | 20 | 8/4 | — | 16/4 | |
| Ceftolozane-tazobactam | 30/10 µg | 21 | 17–20 | 16 | 4/4 | 8/4 | 16/4 | |
| Imipenem-relebactam | 10/25 µg | 23 | 20–22 | 19 | 2/4 | 4/4 | 8/4 | |
| Aztreonam | 30 µg | 22 | 16–21 | 15 | 8 | 16 | 32 | |
| Imipenem | 10 µg | 19 | 16–18 | 15 | 2 | 4 | 8 | |
| Meropenem | 10 µg | 19 | 16–18 | 15 | 2 | 4 | 8 | |
| Tobramycin | 10 µg | 19 | 13–18 | 12 | 1 | 2 | 4 | |
| Amikacin ᵁ | 30 µg | 17 | 15–16 | 14 | 16 | 32 | 64 | Urine only |
| Ciprofloxacin | 5 µg | 25 | 19–24 | 18 | 0.5 | 1 | 2 | |
| Levofloxacin | 5 µg | 22 | 15–21 | 14 | 1 | 2 | 4 | |
| Cefiderocol | 30 µg | 18 | 13–17 | 12 | 4 | 8 | 16 | Iron-depleted CAMHB required |
| Colistin / Polymyxin B | MIC only | — | — | — | 2 | — | 4 | ⚠ Disk diffusion unreliable — use MIC only |
Staphylococcus spp.
Table 2C — Including MRSA-specific breakpoints
| Antibiotic | Disk | Zone Diameter (mm) | MIC (µg/mL) | Notes | ||||
|---|---|---|---|---|---|---|---|---|
| S ≥ | I | R ≤ | S ≤ | I | R ≥ | |||
| Penicillin | 10 units | 29 | — | 28 | 0.12 | — | 0.25 | Confirm susceptible results |
| Oxacillin / MRSA screen | Cefoxitin 30 µg | 22 | — | 21 | ≤2 | — | ≥4 | Cefoxitin is surrogate; MIC for oxacillin |
| Ceftaroline (MRSA) | 30 µg | 25 | 20–24 | 19 | 1 | 2–4 | 8 | S. aureus incl. MRSA |
| Vancomycin (S. aureus) | MIC only | — | — | — | 2 | 4–8 | 16 | ⚠ Disk diffusion unreliable — use MIC only |
| Daptomycin | MIC only | — | — | — | 1 | — | — | ⚠ Disk diffusion unreliable |
| Erythromycin | 15 µg | 23 | 14–22 | 13 | 0.5 | 1–4 | 8 | Predicts azithromycin/clarithromycin |
| Clindamycin | 2 µg | 21 | 15–20 | 14 | 0.5 | 1–2 | 4 | Check D-zone if ery-R, clin-S |
| Tetracycline | 30 µg | 19 | 15–18 | 14 | 4 | 8 | 16 | |
| Doxycycline | 30 µg | 16 | 13–15 | 12 | 4 | 8 | 16 | |
| Ciprofloxacin | 5 µg | 21 | 16–20 | 15 | 1 | 2 | 4 | |
| Levofloxacin | 5 µg | 19 | 16–18 | 15 | 1 | 2 | 4 | |
| Trimethoprim-sulfamethoxazole | 1.25/23.75 µg | 16 | 11–15 | 10 | 2/38 | — | 4/76 | |
| Linezolid | 30 µg | 26 | 23–25 | 22 | 4 | — | 8 | Any growth = resistant |
| Rifampin | 5 µg | 20 | 17–19 | 16 | 1 | 2 | 4 | Never use alone |
| Gentamicin | 10 µg | 15 | 13–14 | 12 | 4 | 8 | 16 | Use only in combination |
| Chloramphenicol | 30 µg | 18 | 13–17 | 12 | 8 | 16 | 32 | |
Enterococcus spp.
Table 2D — E. faecalis, E. faecium
| Antibiotic | Disk | Zone Diameter (mm) | MIC (µg/mL) | Notes | ||||
|---|---|---|---|---|---|---|---|---|
| S ≥ | I | R ≤ | S ≤ | I | R ≥ | |||
| Ampicillin | 10 µg | 17 | — | — | 8 | — | — | No resistant breakpoint |
| Penicillin | 10 units | 15 | — | — | 8 | — | — | No resistant breakpoint |
| Vancomycin | 30 µg | 17 | 15–16 | 14 | 4 | 8–16 | 32 | VRE screening critical |
| Linezolid | 30 µg | 23 | 21–22 | 20 | 2 | 4 | 8 | |
| Daptomycin (E. faecalis) | MIC only | — | — | — | 4 | — | — | MIC only |
| Tetracycline | 30 µg | 19 | 15–18 | 14 | 4 | 8 | 16 | |
| Erythromycin | 15 µg | 23 | 14–22 | 13 | 0.5 | 1–4 | 8 | Predictive value limited |
| Rifampin | 5 µg | 20 | 17–19 | 16 | 1 | 2 | 4 | Combination therapy only |
Haemophilus influenzae
Table 2E — Tested on Haemophilus Test Medium (HTM)
| Antibiotic | Disk | Zone Diameter (mm) | MIC (µg/mL) | Notes | ||||
|---|---|---|---|---|---|---|---|---|
| S ≥ | I | R ≤ | S ≤ | I | R ≥ | |||
| Ampicillin | 10 µg | 22 | 19–21 | 18 | 1 | 2 | 4 | β-lactamase testing recommended |
| Amoxicillin-clavulanate | 20/10 µg | 20 | 17–19 | 16 | 4/2 | 8/4 | 16/8 | |
| Ceftriaxone | 30 µg | 26 | — | — | 2 | — | — | No resistant breakpoint |
| Azithromycin | 15 µg | 12 | — | — | 4 | — | — | No resistant breakpoint |
| Ciprofloxacin | 5 µg | 21 | — | — | 1 | — | — | No resistant breakpoint |
| Levofloxacin | 5 µg | 17 | — | — | 2 | — | — | |
| Trimethoprim-sulfamethoxazole | 1.25/23.75 µg | 16 | 11–15 | 10 | 0.5/9.5 | 1/19–2/38 | 4/76 | |
| Tetracycline | 30 µg | 29 | 26–28 | 25 | 2 | 4 | 8 | |
| Chloramphenicol | 30 µg | 29 | 26–28 | 25 | 2 | 4 | 8 | CSF isolates: always report |
| Rifampin | 5 µg | 20 | 17–19 | 16 | 1 | 2 | 4 | Prophylaxis contacts only |
Streptococcus pneumoniae
Table 2G — Tested on MHA + 5% defibrinated sheep blood
| Antibiotic | Disk | Zone Diameter (mm) | MIC (µg/mL) | Notes | ||||
|---|---|---|---|---|---|---|---|---|
| S ≥ | I | R ≤ | S ≤ | I | R ≥ | |||
| Penicillin (non-meningitis) | Oxacillin screen | ≥20 | — | — | 0.06 | 0.12–1 | 2 | ⚠ If oxacillin ≤19mm, perform MIC |
| Penicillin (meningitis/CSF) | MIC only | — | — | — | 0.06 | — | 0.12 | Meningitis breakpoints only |
| Erythromycin | 15 µg | 21 | 16–20 | 15 | 0.25 | 0.5 | 1 | Predicts azithromycin/clarithromycin |
| Clindamycin | 2 µg | 19 | 16–18 | 15 | 0.25 | 0.5 | 1 | ICR test if Ery-R |
| Levofloxacin | 5 µg | 17 | 14–16 | 13 | 2 | 4 | 8 | S predicts moxifloxacin |
| Vancomycin | 30 µg | 17 | — | — | 1 | — | — | No resistant breakpoint |
| Trimethoprim-sulfamethoxazole | 1.25/23.75 µg | 19 | 16–18 | 15 | 0.5/9.5 | 1/19–2/38 | 4/76 | |
| Doxycycline | 30 µg | 28 | 25–27 | 24 | 0.25 | 0.5 | 1 | |
| Chloramphenicol | 30 µg | 21 | 19–20 | 18 | 4 | 8 | 16 | |
| Linezolid | 30 µg | 21 | — | — | 2 | — | — | No resistant breakpoint |
Streptococcus spp. — β-Hemolytic Groups
Table 2H-1 — Group A, B, C, G — Tested on MHA + 5% sheep blood
| Antibiotic | Disk | Zone Diameter (mm) | MIC (µg/mL) | Notes | ||||
|---|---|---|---|---|---|---|---|---|
| S ≥ | I | R ≤ | S ≤ | I | R ≥ | |||
| Penicillin or Ampicillin | — | — | — | — | 0.12/0.25 | — | — | ⚠ Resistance extremely rare; never report R without confirmation |
| Erythromycin | 15 µg | 21 | 16–20 | 15 | 0.25 | 0.5 | 1 | Predicts azithromycin/clarithromycin |
| Clindamycin | 2 µg | 19 | 16–18 | 15 | 0.25 | 0.5 | 1 | D-zone test required if Ery-R |
| Vancomycin | 30 µg | 17 | — | — | 1 | — | — | No resistant breakpoint |
| Levofloxacin | 5 µg | 17 | 14–16 | 13 | 2 | 4 | 8 | |
| Tetracycline | 30 µg | 23 | 19–22 | 18 | 2 | 4 | 8 | |
| Linezolid | 30 µg | 21 | — | — | 2 | — | — | No resistant breakpoint |
| Chloramphenicol | 30 µg | 21 | 19–20 | 18 | 4 | 8 | 16 | |
🛡️ Resistance Reference Lists
Intrinsic & Acquired Resistance — CLSI M100 Ed36 Table 1A
Intrinsic Resistance = natural/inherent resistance present in all strains of that species — encoded in the organism's chromosome; not transferable. Do not test or report as susceptible.
Acquired/Common Resistance = resistance patterns frequently encountered clinically; warrant selective testing or confirmatory methods. Source: CLSI M100 Ed36 Table 1A & genus-specific notes.
Acquired/Common Resistance = resistance patterns frequently encountered clinically; warrant selective testing or confirmatory methods. Source: CLSI M100 Ed36 Table 1A & genus-specific notes.
Enterobacterales (E. coli, Klebsiella, Proteus, Enterobacter, Serratia, Citrobacter)
Family Enterobacteriaceae — includes many clinically significant nosocomial pathogens
Intrinsic Resistance
- Vancomycin (all Enterobacterales — Gram-negative outer membrane barrier)
- Linezolid (Enterobacterales intrinsically resistant)
- Daptomycin (requires Ca²⁺-binding; Gram-negative outer membrane prevents access)
- Fusidic acid (outer membrane impermeability)
- Glycopeptides (vancomycin, teicoplanin) — all Gram-negatives
- Klebsiella spp. — intrinsically resistant to Ampicillin (chromosomal SHV β-lactamase)
- Enterobacter, Serratia, Citrobacter — AmpC β-lactamase (inducible); may appear susceptible but can de-repress on treatment
- Proteus mirabilis — intrinsically resistant to Nitrofurantoin, Polymyxins (colistin), Tetracycline
- Proteus vulgaris — resistant to Ampicillin, Cephalothin
- Morganella morganii — resistant to Ampicillin, Amoxicillin-clavulanate, Cephalothin, Colistin, Nitrofurantoin
- Providencia spp. — resistant to Colistin, Nitrofurantoin, Tetracycline
⚠ Gram-negative organisms are intrinsically resistant to glycopeptides (vancomycin, teicoplanin) due to the outer membrane lipopolysaccharide barrier preventing drug access to cell wall target.
Frequently Acquired Resistance
- ESBL (Extended-Spectrum β-Lactamases) — CTX-M, SHV, TEM variants; resistance to all penicillins, cephalosporins, aztreonam
- Carbapenem resistance via KPC, NDM, OXA-48, VIM, IMP carbapenemases (CRE)
- Plasmid-mediated AmpC (CMY-2) — cephalosporin resistance
- Fluoroquinolone resistance (PMQR, gyrA/parC mutations)
- Aminoglycoside resistance (AMEs — AAC, ANT, APH enzymes)
- Colistin resistance (mcr-1 plasmid; LPS modification)
- Trimethoprim-sulfamethoxazole resistance (dhfr, sul genes)
ESBL-producing strains: treat cephalosporins, penicillins, aztreonam as resistant regardless of in-vitro results. Confirm with double-disk synergy test or automated ID system.
Pseudomonas aeruginosa
Non-fermenting Gram-negative rod — significant nosocomial pathogen with multiple resistance mechanisms
Intrinsic Resistance
- Vancomycin (Gram-negative outer membrane)
- Ampicillin, Amoxicillin, Amoxicillin-clavulanate (chromosomal AmpC + low outer membrane permeability)
- 1st and 2nd generation cephalosporins (e.g., cefazolin, cefuroxime)
- Trimethoprim (intrinsic insensitivity)
- Ertapenem (intrinsic resistance; OprD efflux)
- Linezolid, Daptomycin, Glycopeptides
- Chloramphenicol (MexAB-OprM efflux pump)
- Tetracyclines (MexAB-OprM efflux; reduced porin uptake)
- Nitrofurantoin
Frequently Acquired Resistance
- Carbapenem resistance: OprD porin loss, overexpression of MexAB-OprM, VIM/IMP/NDM/SPM metallo-β-lactamases
- ESBL / overexpressed AmpC (cephalosporin resistance)
- Fluoroquinolone resistance (GyrA/ParC mutations + efflux upregulation)
- Aminoglycoside resistance (AMEs, 16S rRNA methylases, efflux)
- Colistin resistance (LPS modification, PmrAB/PhoPQ mutations)
- Multi-drug resistant (MDR) / Extensively drug resistant (XDR) strains — common in ICU patients, CF lung
MDR P. aeruginosa: consider newer agents — ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, cefiderocol.
Staphylococcus spp. (S. aureus, CoNS)
Gram-positive cocci; MRSA and VRSA are critical resistance phenotypes
Intrinsic Resistance
- Aztreonam (Gram-positive outer wall; target absent)
- Nalidixic acid (intrinsically resistant)
- Polymyxins / Colistin (Gram-positive cell wall; no LPS target)
- Trimethoprim — S. aureus has low intrinsic susceptibility; always use TMP-SMX combination
- S. saprophyticus: intrinsically resistant to Novobiocin (disc test used for species ID)
Frequently Acquired Resistance
- MRSA (methicillin-resistant): mecA or mecC gene (PBP2a) — resistant to ALL β-lactams except ceftaroline, ceftobiprole
- VRSA/VISA (vancomycin intermediate/resistant): vanA gene acquisition or cell wall thickening
- Penicillinase (β-lactamase TEM/SHV): penicillin resistance in >90% isolates
- Macrolide resistance: erm genes (erythromycin-clindamycin cross-resistance); efflux (mefA)
- Inducible clindamycin resistance (iMLSB): screen with D-zone test (erythromycin + clindamycin disks)
- Fluoroquinolone resistance (GyrA/GrlA mutations)
- Tetracycline/doxycycline resistance (tetK, tetM genes)
- Linezolid resistance (cfr gene, 23S rRNA mutations) — rare
- Fusidic acid resistance (fusA mutations)
- Mupirocin resistance: high-level (ileS2 gene, MIC >512 µg/mL) — MRSA decolonization concern
MRSA detection: Cefoxitin disk (30 µg) is the CLSI-preferred surrogate marker. Zone ≥22 mm = oxacillin-susceptible (MSSA); ≤21 mm = MRSA. mecA PCR is gold standard.
Enterococcus spp. (E. faecalis, E. faecium)
Gram-positive cocci; VRE is a major infection control concern
Intrinsic Resistance
- Cephalosporins — all generations (low PBP affinity)
- Clindamycin (efflux pump, reduced target affinity)
- Aminoglycosides at low levels (cell wall/membrane barrier reduces uptake); high-level synergy testing required
- Trimethoprim (some folate scavenging; clinical outcomes poor)
- Aztreonam and monobactams
- Polymyxins / Colistin
- Nafcillin, Oxacillin (low PBP2 affinity)
- E. faecium: intrinsically resistant to Ampicillin at higher MICs than E. faecalis
Frequently Acquired Resistance
- VRE — Vancomycin-resistant Enterococci: vanA (high-level resistance, ≥64 µg/mL), vanB (variable), vanC (E. gallinarum, E. casseliflavus — intrinsic low-level)
- High-level aminoglycoside resistance (HLAR): gentamicin MIC ≥500; synergy lost — bifurcated treatment needed
- Ampicillin resistance (E. faecium): PBP5 alteration; common in nosocomial E. faecium
- Linezolid resistance: cfr, optrA, poxtA genes; 23S rRNA mutations
- Daptomycin resistance: LiaFSR pathway mutations; cell membrane remodeling
- Fluoroquinolone resistance (GyrA/ParC mutations)
VRE screening: Use vancomycin disk (30 µg). Zone ≤14 mm requires MIC confirmation. VanA/vanB gene detection by PCR is definitive. Isolate VRE patients for infection control.
Haemophilus influenzae & H. parainfluenzae
Fastidious Gram-negative coccobacillus — requires HTM for testing
Intrinsic Resistance
- Vancomycin (Gram-negative outer membrane)
- Clindamycin (outer membrane impermeability)
- Daptomycin, Linezolid (not clinically active)
- Oxacillin (not tested/reported for Haemophilus)
- Cefazolin (poor activity against Haemophilus spp.)
Frequently Acquired Resistance
- β-lactamase-positive strains: ampicillin/amoxicillin resistance (TEM-1 β-lactamase) — ~30–40% of isolates
- BLNAR (β-lactamase-negative, ampicillin-resistant): ftsI (PBP3) mutations — low penicillin-binding affinity
- BLPACR (β-lactamase-positive, amoxicillin-clavulanate-resistant)
- Trimethoprim-sulfamethoxazole resistance (dhfr, sul genes)
- Tetracycline resistance (tetB gene)
- Chloramphenicol resistance (CAT enzyme) — less common
β-lactamase detection is mandatory for all significant H. influenzae isolates. Use nitrocefin disk or chromogenic test. BLNAR strains require MIC testing — disk diffusion may overestimate susceptibility.
Streptococcus pneumoniae
Gram-positive diplococci; α-hemolytic; site-specific breakpoints (meningitis vs. non-meningitis)
Intrinsic Resistance
- Aztreonam (no β-lactamase; no target for monobactams)
- Aminoglycosides (intrinsically low susceptibility; not clinically used alone)
- Trimethoprim alone (low intrinsic activity)
- Colistin / Polymyxins (Gram-positive cell wall structure)
- Metronidazole (obligate anaerobe target; not applicable)
Frequently Acquired Resistance
- Penicillin resistance: PBP2b/2x/1a mutations — PSSP (sensitive), PISP (intermediate), PRSP (resistant)
- Macrolide resistance: erm(B) gene (methylase — cross-resistance with clindamycin) or mefA (efflux)
- Fluoroquinolone resistance: ParC/GyrA mutations (levofloxacin-resistant strains emerging)
- Tetracycline resistance: tetM (ribosomal protection)
- TMP-SMX resistance: dhfr, sul mutations (high resistance rates in many regions)
- Multidrug-resistant S. pneumoniae (MDRSP): resistant to ≥3 drug classes
Penicillin susceptibility: Use 1 µg oxacillin disk screen. Zone ≥20 mm = likely susceptible (MIC ≤0.06 µg/mL). Zone ≤19 mm: perform MIC by broth microdilution with site-specific (meningitis vs. non-meningitis) breakpoints.
Streptococcus spp. — β-Hemolytic Groups (A, B, C, G)
Group A = S. pyogenes; Group B = S. agalactiae; Groups C, G = S. dysgalactiae
Intrinsic Resistance
- Aminoglycosides (intrinsic low-level; use synergy testing for serious infections)
- Nalidixic acid (no target activity in Gram-positive)
- Aztreonam
- Colistin / Polymyxins
- Metronidazole (obligate aerobe; not applicable)
Frequently Acquired Resistance
- Macrolide resistance: erm(B)/erm(TR) — constitutive or inducible MLSB; mefA efflux
- Inducible clindamycin resistance (iMLSB): D-zone test mandatory when ery-R, clin-S
- Tetracycline resistance (tetM, tetO)
- Fluoroquinolone resistance: less common, but increasing in GAS
- TMP-SMX — not clinically reliable for streptococcal infections
- Penicillin resistance in GAS (S. pyogenes) — never reported in >80 years; always report as susceptible without testing
Group A Streptococcus (GAS): Penicillin/ampicillin resistance has NEVER been documented. Never report GAS as penicillin-resistant. D-zone test is mandatory for iMLSB detection before reporting clindamycin as susceptible.
Acinetobacter baumannii complex (CRAB)
Non-fermenting Gram-negative coccobacillus — critical WHO priority pathogen
Intrinsic Resistance
- Vancomycin (Gram-negative outer membrane)
- Linezolid, Daptomycin
- Ertapenem (chromosomal PBP + intrinsic OXA-51-like carbapenemase)
- Penicillin (low affinity + intrinsic β-lactamase)
- Fusidic acid
- Trimethoprim alone
Frequently Acquired Resistance
- Carbapenem resistance: OXA-23, OXA-24/40, OXA-58 (acquired OXA carbapenemases); NDM metallo-β-lactamase
- Pandrug resistance (PDR) — resistant to ALL available antibiotics in some strains
- Aminoglycoside resistance (AMEs + 16S rRNA methylases)
- Fluoroquinolone resistance (GyrA/ParC mutations + AdeABC efflux)
- Tigecycline resistance (AdeABC/AdeIJK efflux pump overexpression)
- Colistin resistance (LPS modification: lpxA/C/D mutations, mcr genes)
CRAB (Carbapenem-Resistant Acinetobacter baumannii): WHO Critical Priority. Active agents — sulbactam-durlobactam, cefiderocol. Colistin + carbapenems (PD dosing) for limited options. Always request MIC testing.
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