Staphylococcus & Streptococcus
OVERVIEW
Macrolides (erythromycin, azithromycin, and clarithromycin) and clindamycin are widely used in healthcare settings, including clinics, dental offices, acute and post-acute care, and surgical centers. Empiric use of these antibiotics is heavily concentrated on the treatment of suspected Staphylococcal and Streptococcal infections, especially in penicillin allergic patients. Empiric use often surpasses directed therapy based upon known culture and susceptibility.
- Macrolides and clindamycin are included in national guideline recommendations for empiric treatment (SSTI’s, Oral-maxillofacial infections, respiratory tract infections), and the prevention of infection (intrapartum prophylaxis, surgical prophylaxis, dental prophylaxis).
- Azithromycin is commonly prescribed for empiric treatment of upper and lower respiratory tract infections by primary care, urgent care and emergency care centers and hospitals.
- Clindamycin is a commonly used as empiric treatment and surgical prophylaxis in PCN-allergic patients. An estimated 7-16% of the population report PCN allergy.
Empirical use of an anti-infective agent requires knowledge of local susceptibility patterns to ensure effective prophylaxis or treatment. However, overuse of azithromycin in the U.S., particularly for respiratory infections, along with unfavorable pharmacokinetic properties (e.g. long half-life), can drive not only macrolide resistance but also induce clindamycin resistance in streptococci and staphylococci with the ERM gene (target site modification). Exposure to both can then lead to constitutive (stable) resistance in both classes of antibiotics. Macrolide and clindamycin resistance in Staphylococcus aureus, Group A and B Streptococcus, Streptococcus pneumoniae, and other pathogenic alpha-hemolytic streptococci has been increasing nationally for decades. High resistance levels would render these antibiotics unreliable for empiric therapy and peri-operative prophylaxis. In Indiana, thousands are treated with azithromycin and clindamycin annually. Over 1M procedures requiring antibiotic prophylaxis are performed each year, with 7-16% of patients reporting a penicillin allergy.
DATA
Current NHSN data is inadequate to allow for accurate assessment of this resistance in Indiana. A collaborative was established with several Indiana healthcare systems and facilities to obtain sufficient data to assess the extent of this resistance in the state. The data is alarming, especially with high levels of empiric use of azithromycin and clindamycin and prevailing use of clindamycin for surgical, dental, and peripartum prophylaxis in penicillin allergic patients. This suggests many patients, especially those with stated penicillin/ß-lactam allergy are receiving inadequate empiric therapy and peri-operative, dental, and Group B intrapartum prophylaxis. The continued unnecessary high use of azithromycin in Indiana serves to exacerbate the problem.
Current CDC/NHSN national and state level data as well as our ARS collaborative with multiple facilities & systems throughout Indiana indicate a concerning level of macrolide and clindamycin resistance in Staphylococcus & Streptococcus.
Overall Indiana Resistance
*Group A and Group B Streptococcus: a portion of isolates may also be included in ß-hemolytic Streptococcus isolates data.
Macrolide Outpatient Prescriptions – Indiana
Source: IQVIA Data from CDC Antimicrobial Resistance & Patient Safety Portal
RESISTANCE MECHANISM & INDUCTION
Macrolide resistance and cross-resistance to clindamycin is widespread in Staphylococcus & Streptococcus species and clinically significant in multiple areas of use. The high utilization of macrolides and specifically azithromycin can drive this resistance to both antibiotic classes.
Azithromycin’s prolonged half-life (~68hrs) results in extended exposure of organisms to sub-inhibitory tissue levels creating an environment that promotes the development of resistance. These properties along with high use of azithromycin contribute to the development of significant macrolide and clindamycin resistance in Streptococcus & Staphylococcus.
Types of Macrolide Resistance:
- Efflux pumps – Reduces effective antibiotic concentrations, typically causing lower-level resistance.
- Target site modifications (erm gene) – Alteration of 50s ribosomal subunit (antibiotic target site), preventing macrolides and clindamycin binding, leading to high-level resistance.
Staphylococcus and Streptococcus isolates may appear susceptible to clindamycin in vitro but if they possess an inducible erm gene, will become resistant during clindamycin therapy. Antibiotic exposure can also lead to a rise in constitutive (stable) resistance to both classes of antimicrobials.
Risk Factors
- Frequent or prolonged macrolide/clindamycin courses
- Patients with reported penicillin allergy (often receive non-ß-lactam antibiotics like macrolides)
- Living in areas with high macrolide/clindamycin resistance rates
DISEASE STATES
Staphylococcus & Streptococcus related resources for the following disease states were developed to build awareness and provide educational resources.
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APPROACH TO ALLERGY
Reported antibiotic allergy can deleteriously impact antibiotic choice. A reported allergy can trigger use of less effective antibiotics leading to worse outcomes, adverse events and increased resistance. A systematic approach to verifying and managing reported allergies is advised. Interventions range from simple to more complex solutions, but can enable more effective treatment and prophylaxis.
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The information provided on this webpage is intended as general overview and background information. It is not intended to be, and should not be considered to be, medical advice or used in any way for the diagnosis or treatment of any specific medical condition. As to any specific medical condition, you should always seek the advice of a physician or other qualified health care provider. You also should not disregard professional medical advice given directly to you based on information contained on this webpage.