Streptococcus Pneumoniae: Does Antimicrobial Resistance Matter?

Joseph P. Lynch, III, M.D.; George G. Zhanel, Ph.D.


Semin Respir Crit Care Med. 2009;30(2):210-238. 

In This Article

Abstract and Introduction


Over the past 3 decades, antimicrobial resistance among Streptococcus pneumoniae, the most common cause of community-acquired pneumonia (CAP), has escalated dramatically worldwide. In the late 1970s, strains of pneumococci displaying resistance to penicillin were described in South Africa and Spain. By the early 1990s, penicillin-resistant clones of S. pneumoniae spread rapidly across Europe and globally. Additionally, resistance to macrolides and other antibiotic classes escalated in tandem with penicillin resistance. Six international clones (serotypes 6A, 6B, 9V, 14, 19F, 23F) were responsible for most of these resistant isolates. Currently, 15 to 30% of S. pneumoniae worldwide are multidrug-resistant (MDR) (i.e., resistant to ≥ 3 classes of antibiotics). Despite the dramatic escalation in the rate of antimicrobial resistance among pneumococci worldwide, the clinical impact of antimicrobial resistance is difficult to define. Treatment failures due to antibiotic-resistant pneumococci have been reported with meningitis, otitis media, and lower respiratory tract infections, but the relation between drug resistance and treatment failures has not been convincingly established. Clinical failures often reflect factors independent of antimicrobial susceptibility of the infecting organisms. Host factors (e.g., extremes of age; underlying immunosuppressive or debilitating disease; comorbidities), or factors that affect intrinsic virulence of the organisms (e.g., capsular subtype) strongly influence prognosis. Mortality rates are higher in the presence of: multilobar involvement, renal insufficiency, need for intensive care unit (ICU) care, hypoxemia, severe derangement in physiological parameters, and comorbidities. Given these confounding factors, dissecting out the impact of antimicrobial resistance on clinical outcomes is difficult, if not impossible. Prospective, randomized trials designed to assess the clinical significance of antimicrobial resistance among pneumococci are lacking, and for logistical reasons, will never be done. Does in vitro resistance translate into clinical failures? Should changing resistance patterns modify our choice of therapy for CAP or for suspected pneumococcal pneumonia? In this review, we discuss several facets, including mechanisms of antimicrobial resistance among specific antibiotic classes, epidemiology and spread of antimicrobial resistance determinants regionally and worldwide, risk factors for acquisition and dissemination of resistance, the impact of key international clones displaying multidrug resistance, the clinical impact of antimicrobial resistance, and strategies to limit or curtail antimicrobial resistance among this key respiratory tract pathogen.


Within the past 3 decades, in vitro resistance of S. pneumoniae to β-lactams, macrolides, and other antibiotic classes escalated dramatically throughout the world.[1–4] In a previous article published in this journal, we discussed the issue of heightened resistance to pneumococci worldwide and implications for therapy.[4] The present study includes much of what was contained in that article but incorporates new data published since 2005 and summarizes current trends and recommendations. Following the initial detection of penicillin-nonsusceptible S. pneumoniae (PNSP) in a few geographic regions (e.g., South Africa, Australia, Spain) in the 1970s,[1,5] resistance spread rapidly worldwide.[4,6,7] The dramatic escalation of antimicrobial resistance globally is due to dissemination of a few international (pandemic) clones.[8] The Pneumococcal Molecular Epidemiology Network classifies international clones according to the country where the strain was first identified, the serotype of the initial clone, and the clone number assigned by the network (e.g., Spain23F-1, Spain6B-2, France9V-3, Tennessee23F-4, England14-9, Taiwan19F-14, Sweden15A-25, Greece21-30, Netherlands15B-37, etc.).[4,8,9] Six serotypes (i.e., 6A, 6B, 9V, 14, 19F, 23F) account for > 80% of penicillin- or macrolide-resistant S. pneumoniae worldwide.[4] The prevalence of specific clones is variable among regions/countries and changes over time.[4,8,10] Spread of resistant strains is facilitated by selection pressure from antibiotic use.[4,11] Clonal spread is an important mechanism for dissemination of resistance to β-lactam and macrolide antibiotics,[4,12–15] whereas resistance to fluoroquinolones (FQs) is usually due to spontaneous de novo mutations rather than clonal dissemination.[4,16–20] However, clonal spread of FQ-resistant pneumococci has been noted.[21–23] Some clones spread rapidly and may persist in a country for years.[24,25] In Sweden, reduction in antibiotic consumption is credited for halting the spread of PNSP in southern Sweden.[24]