ppi-0903 and Pneumococcal-Infections

Ceftaroline is one of latest additions to the armamentarium for treating community-acquired pneumonia (CAP). This study aimed to describe the outcome of severe CAP (SCAP) in a cohort of hospitalised patients treated with ceftaroline.. A retrospective, observational study of patients with SCAP treated with ceftaroline in two hospitals in Spain and Italy. The primary objective was to explore 30-day mortality after diagnosis of SCAP.. During the study period the following were observed: there were 89 cases of SCAP treated with ceftaroline and 53 cases used in combination with other antibiotics (60%). Overall, 30-day mortality and clinical failure were 20% (18 of 89) and 36% (32 of 89), respectively. Independent predictors of 30-day mortality were: increasing age (OR for 1 year increase 1.0, 95% CI 1.0-1.1, P 0.043), presence of solid neoplasm (OR 4.0, 95% CI 1.0-15.1, P 0.044) and concomitant therapy with oseltamivir (OR 8.5, 95% CI 1.2°57.3, P 0.029). The only independent predictor of clinical failure was the time elapsing from SCAP diagnosis to ceftaroline therapy (OR for each passing day 1.5, 95% CI 1.1-1.9, P 0.003). The clinical success rate was 64% (57 of 89). In the subgroups of patients with proven Streptococcus pneumoniae, methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) infection, clinical success was 83% (10 of 12), 75% (three of four) and 56% (five of nine), respectively.. Considering its spectrum of activity, ceftaroline could represent an important therapeutic option for SCAP. Further studies are needed to identify the precise clinical success rate against MRSA in a larger cohort of patients with SCAP.

Topics: Aged; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Community-Acquired Infections; Female; Humans; Italy; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Oseltamivir; Pneumococcal Infections; Pneumonia; Retrospective Studies; Spain; Staphylococcal Infections; Streptococcus pneumoniae

Totals of 8.7% (103/1,190) and 21.0% (249/1,190) of the Streptococcus pneumoniae isolates recovered from specimens collected in the United States during the 2011-2012 AWARE (Assessing Worldwide Antimicrobial Resistance Evaluation) Surveillance Program were ceftriaxone nonsusceptible according to the CLSI (≤ 1 μg/ml for susceptible) and EUCAST (≤ 0.5 μg/ml for susceptible) criteria, respectively. Decreased susceptibility to ceftriaxone (MIC, 1 μg/ml) was frequently observed among serotypes 19 A (51.4%; 128/249) and 35 B (29.7%; 74/249), which were most often observed in the East South Central and South Atlantic U.S. Census regions. Ceftaroline (MIC50/90, 0.12/0.25 μg/ml) remained active (≥ 96.8% susceptible) when tested against these less susceptible isolates.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Ceftaroline; Ceftriaxone; Cephalosporins; Humans; Microbial Sensitivity Tests; Molecular Epidemiology; Pneumococcal Infections; Serogroup; Serotyping; Streptococcus pneumoniae; United States

Ongoing surveillance for Streptococcus pneumoniae is needed to assess the impact of the pneumococcal conjugate vaccine introduced in 2010 (PCV13). Forty-two U.S. centers submitted S. pneumoniae isolates between 1 October 2012 and 31 March 2013. Susceptibility testing was performed by use of a broth dilution method as recommended by the Clinical and Laboratory Standards Institute. Serotyping was performed by multiplex PCR and the Quellung reaction. Multidrug resistance (MDR) was defined as nonsusceptibility to penicillin (PNSP; MIC ≥ 0.12 μg/ml) combined with resistance to ≥2 non-β-lactam antimicrobials. Penicillin-resistant S. pneumoniae (PRSP) was defined as a penicillin MIC of ≥2 μg/ml. For the 1,498 isolates collected during 2012-13, the PRSP and MDR rates were 14.2 and 21.0%, respectively. These percentages were lower than rates obtained in a surveillance study conducted 4 years earlier in 2008-09 (17.0 and 26.6%, respectively). The most common serotypes identified in 2012-13 were 3, 35B, and 19A, each representing 9 to 10% of all isolates. The largest percentage of PNSP in 2012-13 were found in serotypes 35B (24.8%), 19A (23.5%), and 15A (10.3%). Predominant PRSP serotypes were 19A (54.5%), 35B (28.2%), and 19F (7.0%). Major MDR serotypes were 19A (38.5%), 15A (16.9%), 6C (8.3%), and 35B (6.4%). The change in prevalence of PCV13 serotypes (43.4 to 27.1%) was primarily due to a decrease in serotype 19A strains, i.e., 22% of all strains in 2008-09 to 10% of all strains in 2012-13. Among the PNSP subset, serotypes showing a proportional increase were 35B, 15B, and 23B. Among MDR strains, the largest proportional increases were observed in serotypes 35B, 15B, and 23A.

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Drug Resistance, Multiple, Bacterial; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Serotyping; Streptococcus pneumoniae; United States; Vaccines, Conjugate

A 14-year longitudinal survey of Streptococcus pneumoniae (18,911) strains by the SENTRY Antimicrobial Surveillance Program shows significant increases in resistance to amoxicillin/clavulanate (18.9%), penicillin at a MIC of ≥ 4 μg/mL (14.8%), and ceftriaxone (11.7%) among 2011 isolates. Fluoroquinolones (levofloxacin; 98.8% susceptible) and ceftaroline (99.1-100.0% susceptible depending on breakpoint criteria) exhibited high levels of potency, as did linezolid, tigecycline, and vancomycin (100.0%). In summary, resistance rates to several antimicrobials continue to rise after introductions of both pneumococcal conjugate vaccines, as noted from these results for 1998 through 2011.

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Longitudinal Studies; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae; United States

This study assessed the pharmacodynamics of ceftaroline against penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae with elevated MICs of ceftaroline using an in vitro pharmacodynamic model.. Nine isolates of S. pneumoniae, including one penicillin-susceptible isolate, one penicillin-intermediate isolate and seven penicillin-resistant isolates, were tested. The pharmacodynamic model was inoculated with a concentration of 1 × 10(6) cfu/mL and ceftaroline was dosed twice daily (at 0 and 12 h) to simulate the fC(max) (maximum free concentration in serum) and t(1/2) (half-life in serum) obtained after 600 mg intravenous doses every 12 h (fC(max), 16 mg/L; t(1/2), 2.6 h). Ceftaroline was compared with ceftriaxone dosed once daily to simulate the fC(max) and t(1/2) obtained after a 1 g dose (fC(max), 18 mg/L; t(1/2), 8.0 h). Samples were collected over 24 h to assess viable growth and possible changes in ceftaroline MICs over time.. Ceftaroline fT(>MIC) (time of free serum concentration over the MIC) of 100% (ceftaroline MICs, ≤ 0.5 mg/L) was bactericidal (≥ 3 log(10) killing) against all isolates at 6 h and completely eradicated all organisms at 12 and 24 h. No bacterial regrowth occurred over the study period and no changes in ceftaroline MICs were observed. Upon ceftriaxone exposure, S. pneumoniae isolates with ceftriaxone MICs of 0.12 and 0.25 mg/L were eradicated, but isolates with ceftriaxone MICs of 1-8 mg/L resulted in initial bacterial reduction at 6 h with organism regrowth at 12 h and no reduction in organism concentration, relative to the starting inoculum, at 24 h.. Ceftaroline fT(>MIC) of 100% (ceftaroline MICs, ≤ 0.5 mg/L) was bactericidal (≥ 3 log(10) killing) and eradicated all S. pneumoniae at 12 and 24 h with no regrowth.

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Microbial Viability; Models, Theoretical; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae

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.

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Communicable Diseases, Emerging; Drug Resistance, Multiple, Bacterial; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; United States

Increasing pneumococcal resistance to extended-spectrum cephalosporins warrants the search for novel agents with activity against such resistant strains. Ceftaroline, a parenteral cephalosporin currently in phase 3 clinical development, has demonstrated potent in vitro activity against resistant gram-positive organisms, including penicillin-resistant Streptococcus pneumoniae. In this study, the activity of ceftaroline was evaluated against highly cefotaxime-resistant isolates of pneumococci from the Active Bacterial Core surveillance program of the Centers for Disease Control and Prevention and against laboratory-derived cephalosporin-resistant mutants of S. pneumoniae. The MICs of ceftaroline and comparators were determined by broth microdilution. In total, 120 U.S. isolates of cefotaxime-resistant (MIC > or = 4 microg/ml) S. pneumoniae were tested along with 18 laboratory-derived R6 strains with known penicillin-binding protein (PBP) mutations. Clinical isolates were characterized by multilocus sequence typing, and the DNAs of selected isolates were sequenced to identify mutations affecting pbp genes. Ceftaroline (MIC(90) = 0.5 microg/ml) had greater in vitro activity than penicillin, cefotaxime, or ceftriaxone (MIC(90) = 8 microg/ml for all comparators) against the set of highly cephalosporin-resistant clinical isolates of S. pneumoniae. Ceftaroline was also more active against the defined R6 PBP mutant strains, which suggests that ceftaroline can overcome common mechanisms of PBP-mediated cephalosporin resistance. These data indicate that ceftaroline has significant potency against S. pneumoniae strains resistant to existing parenteral cephalosporins and support its continued development for the treatment of infections caused by resistant S. pneumoniae strains.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Typing Techniques; Ceftaroline; Cephalosporins; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Penicillin-Binding Proteins; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Amoxicillin; Anti-Bacterial Agents; Cefotaxime; Ceftaroline; Cephalosporin Resistance; Cephalosporins; Drug Resistance, Multiple, Bacterial; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae