Extrapolating antibiotic susceptibility for streptococci including the pneumococcus

This posting concerns betahaemolytic species of streptococci including S. pyogenes (Lancefield group A strep), S. agalactiae ((group B strep), S. dysgalactiae group (betahaemolytic large colony, groups C or G) (several species included) which are usually associated with pyogenic infection, especially of skin and soft tissue.   S. pneumoniae (the pneumococcus ) is also considered. 

A key misunderstanding about Streptococcus pneumoniae is the significance of penicillin ‘resistance’ and how it is detected.  Oxacillin is used because it provides the best sensitivity for detection of minor elevation of the penicillin minimal inhibitory concentration (MIC) that may be associated with failure of meningitis treatment. Note that benzylpenicillin, ampicillin or amoxycillin remain highly effective therapy for non-meningeal infection (e.g. pneumonia) caused by strains with lowered susceptibility (raised MIC), unless the MIC is (unusually) >=4mg/L when an alternative agent should be selected.   For a useful review of the situation in regards betalactam and macrolide resistance see this 2007 review by Keith Klugman and the paper by Schentag et al referenced below.

Indicator antibiotic tested Result Extrapolates to Notes


Groups A, B, C & G betahaemolytic species of streptococci only






ampicillin/ amoxycillin








Clinically significant penicillin resistance has NOT been recorded in these species.

Betalactamases are NOT found in any Streptococcus species; hence betalactamase inhibitors (e.g. clavulanate or tazobactam) offer no advantages.






Oxacillin screen (disc)

Streptococcus pneumoniae only


Both EUCAST and CLSI rely on this screening test.



(Equates to penicillin MIC of <=0.06mg/L)

as above


All types of oxacillin susceptible pneumococcal infections can be treated with benzylpenicillin.



(Resistance is due to altered penicillin binding proteins derived from genes uploaded by process of transformation from related oral Streptococcal species.)

Meningitis – test MIC by E-test to detect raised ceftriaxone MIC (>0.5mg/L)


Non-meningeal infections e.g. pneumonia – do

MIC by E-test to benzylpenicillin1 and report as below2

Do NOT use phenoxymethylpenicillin, cephalexin, cefazolin3, flucloxacillin, ceftazidime, ticarcillin – the MICs will usually be in the resistant range for all oxacillin-resistant strains.



Erythromycin Susceptible Azithromycin




Inducible clindamycin screen (D-Test) can distinguish a subset of clindamycin susceptible, erythromycin resistant strains. However, most labs do not bother with this!
Tetracycline Susceptible Doxycycline



Some strains resistant to tetracycline may be susceptible to doxy or minocycline; however most labs will not test these separately.
Trimethoprim+ sulfamethoxazole Susceptible Nil S. pyogenes (Group A) strains may only test susceptible if low-concentration thymidine agar is used for testing4.


Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group. Arch Intern Med. 2000 May 22;160(10):1399-408

Streptococcus pneumoniae bacteraemia: pharmacodynamic correlations with outcome and macrolideresistance–a controlled study. Schentag JJ et al,Int J Antimicrob Agents. 2007 Sep;30(3):264-9. 

Clinical impact of antibiotic resistance in respiratory tract infections Keith P. Klugman, International Journal of Antimicrobial Agents 29 Suppl. 1 (2007) S6–S10. 

1 If ampicillin IV to be used, then infer susceptibility from ampicillin MIC rather than benzylpenicillin (EUCAST advice).

2  Comment in use at Pathology North derived from EUCAST: In pneumonia, benzylpenicillin 1.2 g IV every 6 hours is adequate treatment for isolates with MIC <=0.5mg/L. Use 1.2 g every 4 hours for isolates with MIC <=1 mg/L. Use 2.4 g every 4 hours for isolates with MIC <=2 mg/L. Alternative therapy should be selected for isolates with MIC >=4 mg/L – please discuss with the on-call clinical microbiologist.

3 This is the reason that phenoxymethylpenicillin and first generation cephalosporins are NOT generally recommended for use in acute community acquired respiratory infections (sinusitis, otitis media or pneumonia).

4 Bowen-AC et al. Is Streptococcus pyogenes resistant or susceptible to trimethoprim-sulfamethoxazole? J Clin Microbiol. 2012 Dec; 50(12):4067-72 (free full text).


  1. […] is NOT recommended for pneumonia even when the penicillin MIC is elevated (MIC < 4 mg/L). This posting provides detailed clinical and lab […]




  3. […] is NOT recommended for pneumonia even when the penicillin MIC is elevated (MIC < 4 mg/L). This posting provides detailed clinical and lab […]


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