Antibiotic resistance and serotypes of at Birmingham public health laboratory, 1989–94

Semin Respir Crit Care Med

Zhanel²

2009

113

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 > or = 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.

Section: Macrolide Resistancementioning

confidence: 99%

Streptococcus pneumoniae: Does Antimicrobial Resistance Matter?

Semin Respir Crit Care Med

Zhanel²

2009

113

“…In South Africa, where MDR was detected in the late 1970s, 5 macrolide resistance remained below 3% by the mid-1990s. 170 Even in the mid-1990s, rates of erythromycin resistance among pneumococci remained low (0-7%) in Denmark, 20 Norway, 321 Finland, 64,297,322,323 Germany, 313,324 Austria, 325 England, 326,327 Wales, 327 and Israel. 71,328 However, recent studies in Germany from 2000-01 cited rates of macrolide resistance of 14.1% 45 and 17.4%, 200 respectively.…”

Section: Concomitant Resistance To Other Antibiotic Classesmentioning

confidence: 99%

Escalation of Antimicrobial Resistance amongStreptococcus pneumoniae: Implications for Therapy

Seminars in Respiratory and Critical Care Medicine

Zhanel

2005

109

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.

“…By the mid1990s, the rate of macrolide resistance remained !3% in South Africa [75]. Similarly, recent surveillance studies cited low rates of erythromycin resistance (0%-7%) among pneumococci in Denmark [129], Norway [130], Finland [131,132], Germany [95,133], Austria [134], England [135,136], Portugal [137], and Israel [106,138].…”

Section: Global Trendsmentioning

confidence: 99%

Clinical Relevance of Macrolide-Resistant Streptococcus pneumoniae for Community-Acquired Pneumonia

Clinical Infectious Diseases

Martínez

2002

117

101

Macrolides are often the first choice for empirical treatment of community-acquired pneumonia. However, macrolide resistance among Streptococcus pneumoniae has escalated at alarming rates in North America and worldwide. Macrolide resistance among pneumococci is primarily due to genetic mutations affecting the ribosomal target site (ermAM) or active drug efflux (mefE). Prior antibiotic exposure is the major risk factor for amplification and perpetuation of resistance. Clonal spread facilitates dissemination of drug-resistant strains. Data assessing the impact of macrolide resistance on clinical outcomes are spare. Many experts believe that the clinical impact is limited. Ribosomal mutations confer high-grade resistance, whereas efflux mutations can likely be overridden in vivo. Favorable pharmacokinetics and pharmacodynamics, high concentrations at sites of infections, and additional properties of macrolides may enhance their efficacy. In this article, we discuss the prevalence of macrolide resistance among S. pneumoniae, risk factors and mechanisms responsible for resistance, therapeutic strategies, and implications for the future.