Activity of ceftaroline against recent emerging serotypes of Streptococcus pneumoniae in the United States.

The in vitro activity of ceftaroline against 891 pneumococci collected in 2008 from 22 centers in the United States was investigated. Ceftaroline was the most potent agent tested, with the MICs being <0.008 to 0.5 microg/ml and the MIC(90)s being <0.008 to 0.25 microg/ml against 11 prevailing serotypes. The overall rates of susceptibility were as follows: penicillin G, 86.2%; ceftriaxone, 90.7%; cefuroxime, 70.1%; erythromycin, 61.6%; clindamycin, 79.2%; levofloxacin, 99.4%; and vancomycin, 100%. Serotype 19A isolates were the least susceptible. These results support the use of ceftaroline for the treatment of pneumococcal infections, including those caused by pneumococci resistant to other agents.

Validation of factor 6d antiserum for serotyping Streptococcus pneumoniae serotype 6C.

Factor 6d antiserum reacts with the new Streptococcus pneumoniae serotype 6C. Serogroup 6 isolates, consisting of 49 6A, 42 6B and 98 6C strains from the United States and Israel, serotyped in parallel by PCR and capsular swelling methods, were all identified correctly. The new factor 6d antiserum accurately identifies serotype 6C.

Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced carbapenem susceptibility.

We studied the accuracy of various susceptibility testing methods, including the 2009, 2010, and updated 2010 CLSI recommendations, to identify Klebsiella pneumoniae isolates with reduced susceptibility to carbapenems associated with different mechanisms of resistance. Forty-three wild-type (WT) strains, 42 extended-spectrum ß-lactamase (ESBL) producers, 18 ESBL producers with outer membrane porin protein loss (ESBL/Omp strains), and 42 blaKPC-possessing K. pneumoniae (KPC-Kp) isolates were evaluated. Imipenem (IPM), meropenem (MEM), ertapenem (ERT), and doripenem (DOR) were tested by broth microdilution (BMD), Etest, and disk diffusion (DD), and the modified Hodge test (MHT) was performed using IPM and MEM disks. Results were interpreted according to original as well as recently updated interpretative criteria. MHT was positive for all 42 KPC-Kp isolates and 10 of 18 ESBL/Omp strains and therefore had poor specificity in differentiating between KPC-Kp and ESBL/Omp isolates. Based on the updated CLSI standards, phenotypic susceptibility testing by BMD and DD differentiated most carbapenem-susceptible from carbapenem-nonsusceptible K. pneumoniae isolates without the need for MHT, while the Etest method characterized many KPC-Kp isolates as susceptible, and breakpoints may need to be lowered for this method. However, both the original and updated CLSI criteria do not adequately differentiate between isolates in the KPC-Kp group, which are unlikely to respond to carbapenem therapy, and those in the ESBL/Omp group, which are likely to respond to carbapenem therapy if MICs are within pharmacokinetic/pharmacodynamic targets. Further studies are required to determine if there is a clinical need to differentiate between KPC-Kp and ESBL/Omp groups.

Occurrence, distribution, and origins of Streptococcus pneumoniae Serotype 6C, a recently recognized serotype.

The prevalence of Streptococcus pneumoniae serotype 6C, a recently recognized serotype that cross-reacts serologically with serotype 6A, was investigated. Isolates of serotype 6A in various collections were recovered, and serotype 6C was differentiated from 6A by multiplex PCR of DNA extracts by using appropriate primers. Antimicrobial susceptibility was performed by Clinical and Laboratory Standards Institute broth microdilution, and selected isolates were typed by pulsed-field gel electrophoresis, repetitive sequence-based PCR typing, and rapid multilocus sequence typing (MLST) by electrospray ionization mass spectrometry of PCR products. A total of 60 serotype 6C isolates were found: 30 of 122 Cleveland isolates collected from 1979 to 2007, 19 of 39 pediatric isolates collected nationwide in 2005 and 2006, and 11 pediatric isolates from Massachusetts collected in 2006 and 2007. Only four isolates were recovered prior to introduction of the conjugate pneumococcal vaccine in 2000; the earliest isolate was recovered in 1989. The sources of the isolates included blood (n = 5), the lower respiratory tract (n = 27), the sinus (n = 5), the ear (n = 2), and the nasopharynx (n = 18); isolates were recovered from 49 children and 11 adults. Pediatric isolates were found in all six major U.S. geographic regions. Antimicrobial susceptibility showed that 22 isolates were nonsusceptible to penicillin, macrolides, and trimethoprim-sulfamethoxazole, 8 had other resistance patterns, and 30 were fully susceptible. The three typing methods used showed similar clusters of up to eight isolates per cluster. MLST showed five clusters related to serotype 6A, two clusters related to serotype 6B, one cluster related to serotype 3, and one cluster related to serotype 34. This study documents the occurrence, nationwide distribution, diversity, likely origins, and increasing incidence after 2001 of this recently recognized serotype. Serotype 6C warrants consideration for addition to future conjugate pneumococcal vaccines.

Emergence of Streptococcus pneumoniae serotypes 19A, 6C, and 22F and serogroup 15 in Cleveland, Ohio, in relation to introduction of the protein-conjugated pneumococcal vaccine.

BACKGROUND: A 7-valent conjugate pneumococcal vaccine (PCV7) was introduced in 2000. METHODS: We determined serotypes and assessed antimicrobial susceptibility of 1235 invasive and noninvasive isolates of Streptococcus pneumoniae recovered from children and adults at University Hospitals Case Medical Center (Cleveland, OH) during the period 1999-2007. RESULTS: The annual number of cases of S. pneumoniae infection decreased from 218 in 2000 to 86-130 during the period 2002-2007, with the number of cases involving invasive strains decreasing from 96 to 18-35. For 1999 versus 2005-2007, the annual incidence of vaccine serotypes decreased by 92% (95% confidence interval [CI], -96.3% to -87.0%), whereas that of vaccine-related and nonvaccine serotypes increased 207.4% (95% CI, 135.0%-297.7%) and 18.4% (95% CI, -10.0% to 52.3%), respectively. Serotypes 19A, 6C, and 22F and serogroup 15 accounted for most of these increases. For the period 2005-2007, antimicrobial susceptibility testing revealed that ceftriaxone was the most active parenteral beta-lactam for both meningeal and nonmeningeal infections (72% and 88% of isolates, respectively, were susceptible to this agent); only 52% were susceptible to penicillin G at the meningeal breakpoint, whereas 77% were susceptible at the new nonmeningeal breakpoint of 2 microg/mL. Amoxicillin was the most active oral beta-lactam (72% of isolates were susceptible), whereas 53% of isolates were susceptible to azithromycin, 69% to clindamycin, 63% to trimethoprim-sulfamethoxazole, and 100% to levofloxacin. CONCLUSIONS: This study documents decreases in the incidence of infections involving vaccine serotypes, increases in infections involving other serotypes, and decreases in the activity of macrolides and clindamycin after conjugate vaccine introduction.

Changes in serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae strains in Cleveland: a quarter century of experience.

The serotypes and susceptibilities to penicillin, macrolides, and clindamycin of 1,655 invasive isolates of Streptococcus pneumoniae recovered between 1979 and 2004 were determined. A precipitous decrease of 61% in the number of isolates was found following 2000, the year of 7-valent protein-conjugated pneumococcal vaccine (PCV7) introduction (139 versus 55 per 2-year period prior to versus after 2000; P < 0.001). This decrease was 84% in children <5 years old (80 versus 13 per 2-year period; P < 0.001) and 18 to 23% in other age groups (P, not significant). PCV7 serotypes decreased by 76% overall (103 versus 25 per 2-year period; P < 0.001) and by 92% in children <5 years old (65 versus 5 per 2-year period; P < 0.001), with significant decreases in six of the seven PCV serotypes. Other serotypes, except for type 19A, decreased from 32 to 22 per 2-year period, while type 19A increased from 4 to 8 per 2-year period, although none of these changes reached significance. Drug resistance emerged slowly, with the first penicillin-intermediate strain isolated in 1980 and the first macrolide/lincosamide-resistant strain isolated in 1984. The first penicillin-resistant strain was isolated in 1993. Resistance increased steadily thereafter until 2003-2004, when 51.1% of isolates were penicillin nonsusceptible and 53.3% were macrolide resistant. Clindamycin resistance remained low until 2003-2004, when 26.7% of strains were resistant; this was associated with the emergence of multidrug-resistant type 19A strains. This study documents the emergence of resistance over a quarter century among invasive pneumococci in the Cleveland area, as well as the reduction in disease caused by PCV7 serotypes following the introduction of PCV7 in 2000.