Risk Factors for Drug-Resistant Streptococcus pneumoniae (DRSP)
The most important risk factors for drug-resistant pneumococcus include age ≥65 years, recent β-lactam antibiotic use within 3 months, alcoholism, multiple medical comorbidities, immunosuppressive conditions, and exposure to children in daycare settings. 1
Primary Risk Factors with Quantified Risk
The American Thoracic Society guidelines identify the following risk factors with associated odds ratios:
- Age ≥65 years: OR 3.8, though one study showed more modest effect with OR 1.2 (95% CI 1.0-1.5), corresponding to 24% DRSP incidence versus 19% in younger adults 1
- Alcoholism: OR 5.2, representing one of the strongest independent predictors 1
- β-lactam antibiotic therapy within 3 months: OR 2.8 1
- Noninvasive disease: OR 4.5 (suggesting possibly reduced virulence of resistant organisms) 1
Additional Established Risk Factors
Multiple medical comorbidities significantly increase DRSP risk and include: 1
- Chronic obstructive pulmonary disease (COPD)
- Congestive heart failure
- Chronic liver disease
- Chronic renal failure or nephrotic syndrome 1
- Diabetes mellitus
- Malignancies (including multiple myeloma, Hodgkin's disease, generalized malignancy) 1
Immunosuppressive conditions represent critical risk factors: 1
- HIV infection/AIDS (annual attack rate as high as 1% or 940 cases per 100,000 population among AIDS patients) 1
- Organ or bone marrow transplantation 1
- Therapy with alkylating agents, antimetabolites, or systemic corticosteroids 1
- Asplenia 1
Environmental and Social Risk Factors
- Exposure to children in daycare centers: Particularly significant for children <2 years (36-fold increased risk), though less clear for adults 1
- Nursing home residence: Associated with higher rates of resistant organisms 1
Clinical Context and Geographic Considerations
Not all patients in areas with high geographic rates of DRSP are equally likely to be infected with resistant organisms. Even in high-resistance areas, organisms isolated from sputum and blood cultures are less commonly resistant than expected based on surveillance data alone. 1
The 2007 IDSA/ATS guidelines recommend considering alternative agents when local macrolide resistance exceeds 25%, as this threshold indicates substantial community resistance burden. 1
Important Clinical Implications
Recent antibiotic exposure within 90 days mandates selection of a different antibiotic class to reduce resistance risk, not just for DRSP but for all potential pathogens. 1, 2
The presence of any DRSP risk factor should prompt empiric therapy with either:
- Respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 mg), OR
- β-lactam plus macrolide combination (high-dose amoxicillin 1g three times daily or amoxicillin-clavulanate 2g twice daily plus azithromycin or clarithromycin) 1, 2
Common Pitfalls to Avoid
Do not assume that age alone without comorbidities substantially changes bacterial etiology for most pathogens—DRSP is unique in that age ≥65 years is an independent risk factor specifically for this organism. 1
Do not use macrolide monotherapy in patients with any DRSP risk factors, as breakthrough pneumococcal bacteremia with macrolide-resistant strains is significantly more common in this population. 1, 2, 3