Escalation of Antimicrobial Resistance amongStreptococcus pneumoniae: Implications for Therapy

Abstract

Over the past 2 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, 20 to 30% of S. pneumoniae worldwide are multidrug resistant (MDR) (i.e., resistant to > or = 3 different 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, determining 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? This review discusses 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 MDR, the clinical impact of antimicrobial resistance, and strategies to limit or curtail antimicrobial resistance among this key respiratory tract pathogen.

A new serotype 14 variant of the pneumococcal Spain9V-3 international clone detected in the central region of Argentina

“…Penicillin-resistant isolates were first detected in the late 1960s, and their prevalence increased rapidly during the 1980s. Since 1989, the incidence of penicillin-resistant pneumococci has remained fairly constant at about 20-30 % of all isolates (Lynch & Zhanel, 2005). Molecular characterization of penicillinresistant strains from around the world has highlighted an important diversity among isolates, but has also identified a number of successful pneumococcal clones with a high level of penicillin resistance, some of which have spread globally (Crook & Spratt, 1998).…”

Transcriptional regulation, occurrence and putative role of the Pht family of Streptococcus pneumoniae

“…The emergence of antibiotic-resistant strains of this micro-organism has further underlined the need for providing effective prophylactic vaccination (Bridy-Pappas et al, 2005;Lynch & Zhanel, 2005).…”

Development of a Vaccine against Invasive Pneumococcal Disease Based on Combinations of Virulence Proteins of Streptococcus pneumoniae

“…In spite of the availability of antimicrobials, the capsular polysaccharide (PS) vaccine, and the 7-valent protein-PS conjugate vaccine, pneumococcal disease continues to cause high morbidity and mortality worldwide, especially in groups at high risk, such as children under 2 years of age, the elderly, and immunocompromised individuals (36). These continuing pneumococcal disease problems have arisen in part due to the increasing rates at which S. pneumoniae is acquiring resistance to multiple antimicrobials (27) but are largely due to the shortcomings associated with the current capsular-based vaccines, including high cost, serotype-specific protection, limited serotype coverage, and the likelihood of a concomitant increase in carriage, and subsequently disease, with nonvaccine serotypes. Consequently, concerted global efforts are currently focused on developing alternative pneumococcal-vaccine strategies that address these shortcomings, without compromising efficacy.…”