Robertino M. Mera

Serotype Replacement and Multiple Resistance in Streptococcus pneumoniae After the Introduction of the Conjugate Pneumococcal Vaccine

BACKGROUND The pneumococcal conjugate vaccine (PCV7), introduced in February 2000, covered 82% of the U.S. pediatric population in 2005. Changes over time in serogroup prevalence and multidrug-resistance (MR) to antimicrobials were evaluated using the U.S. SENTRY surveillance program. METHODS The study included 704 U.S. isolates, with equal numbers before (1998-1999) and after the introduction of the vaccine (2003-2004). Demographic data, serotype, and resistance profiles for five antimicrobial classes were analyzed. Strains displaying resistance to >or=2 classes were considered MR. Statistical analysis was performed using logistic regression. RESULTS Prevalence of PCV7 serotypes was 68.5% in the prevaccine years, dropping to 29.3% in the postvaccine period. Among PCV7 serotypes, only 19F persisted, with nonvaccine (NV) serotype 19nonF strains increasing from 3% to 20% of total p<0.001. NV serotypes were 1.9 times (95% confidence interval [CI] 1.1-3.1) more likely to acquire MR over time. Although PCV7 serotypes constituted 84% of all MR isolates in the prevaccine era, MR was unchanged in the postvaccine period due to increased prevalence and acquisition of resistance by NV serotypes. MR among invasive isolates did not change over time, but increased among noninvasive NV isolates by 17% (95% CI 12-22%). CONCLUSIONS The complete switch in prevalence of PCV7 by NV serotypes has been aided by a herd effect in adults and older children. NV serotypes have acquired MR at a rate that is proportional to the replacement process.

Risk Factors for Development of Multiple-Class Resistance to Streptococcus pneumoniae Strains in Belgium over a 10-Year Period: Antimicrobial Consumption, Population Density, and Geographic Location

ABSTRACT We investigated the impact of the usage of antibiotics in ambulatory patients in Belgium in 147 defined geographical circumscriptions and at the individual isolate level. The study included 14,448 Streptococcus pneumoniae strains collected by the Belgium national reference lab from 1994 to 2004. Additional risk factors for resistance, such as population density/structure and day care attendance, were investigated for the same time-space window. A statistical model that included resistance to two or more antimicrobial classes offered the best fit for measuring the changes in nonsusceptibility to penicillin, macrolides, and tetracycline over time and place in Belgium. Analysis at the geographic level identified antimicrobial consumption with a 1-year lag (0.5% increase per additional defined daily dose) and population density as independent predictors of multiple resistance. Independent risk factors at the isolate level were age (odds ratio [OR], 1.55 for children aged <5 years), population density (7% increase in multiple resistance per 100 inhabitants/km2), conjugate 7-valent vaccine serotype (OR, 14.3), location (OR, 1.55 for regions bordering high-resistance France), and isolate source (OR, 1.54 for ear isolates). The expansion of multiple-resistant strains explains most of the overall twofold increase and subsequent decrease in single antimicrobial resistance between 1994 and 2004. We conclude that factors in addition to antibiotic use, such as high population density and proximity to high-resistance regions, favor multiple resistance. Regional resistance rates are not linearly related to actual antibiotic use but are linked to past antibiotic use plus a combination of demographic and geographic factors.

Prevalence and Sequence Variation of Panton-Valentine Leukocidin in Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Strains in the United States

ABSTRACT Panton-Valentine leukocidin (PVL), encoded by the lukSF-PV genes, is a putative virulence factor and marker for community-associated methicillin-resistant Staphylococcus aureus. Here we report the prevalence of PVL among a representative sample of 1,055 S. aureus infection isolates from the United States and describe the sequence variation of the lukSF-PV genes. We performed multilocus sequence typing (MLST) on all isolates and sequenced fragments of the lukSF-PV genes from a sample of 86 isolates. We assigned isolates to a PVL R or H sequence type based on a polymorphism that results in an amino acid change from arginine (R) to histidine (H). Overall, we found that 36% of S. aureus isolates were positive for lukSF-PV. Among the 86 we typed, we identified 72 R variants and 14 H variants. Among the 47 methicillin-resistance S. aureus (MRSA) isolates, 43 harbored the R variant, and among the 39 methicillin-susceptible S. aureus (MSSA) isolates, 29 harbored the R variant. Almost all (97%) of the R variants were found in MLST clonal complex 8 (CC8), while the H variant was broadly distributed among 6 CCs. Within CC8, all 38 MRSA (USA300) and all 28 MSSA isolates harbored the R variant. Of the 20 isolates from blood and the lower respiratory tract, 19 (95%) harbored the R variant. While the R variant had been linked primarily to USA300 MRSA, we found that all CC8 MSSA isolates also contained the R variant, suggesting that some strains of USA300 may have lost methicillin resistance as an adaptation in the community.

Effect of Eradication of Helicobacter Pylori and Iron Supplementation on the Iron Status of Children with Iron Deficiency

BACKGROUND AND AIMS We undertook this study to evaluate the effect of Helicobacter pylori eradication and iron supplementation on the iron nutritional status in children with iron deficiency. METHODS Seven hundred and one children from four public schools in Mexico City were screened to evaluate their iron status. Of them, 72 children with iron deficiency or with anemia were included in this study and were tested for H. pylori infection. Those infected were given eradication treatment and were randomly assigned to daily supplementation for 3 months with ferrous sulfate or placebo. Noninfected children received ferrous sulfate. At the end of the interventions, blood samples were drawn to evaluate their effects on the nutritional status of iron. RESULTS Thirty eight children with iron deficiency or anemia were infected by H. pylori at baseline. The eradication rate was 86.8%. Children in whom H. pylori eradication was achieved showed an increase of 0.37g/dL (95% CI -0.02, 0.75) on the hemoglobin mean concentration compared to the noninfected children. Children who achieved H. pylori eradication and received ferrous sulfate supplementation showed an increase of 0.47g/dL (95% CI 0.01-0.93) on the hemoglobin mean concentration compared to the noninfected children who received iron supplementation. Noninfected children supplemented with ferrous sulfate showed an increase in ferritin concentration of 11.26 ng/mL (95% CI 1.86-20.65) compared to those who were given the placebo. CONCLUSIONS Our results suggest that the eradication of H. pylori plus iron supplementation increases the pool of functional iron. Iron supplementation increases the storage of iron in school-age children with iron deficiency.

Temporal and Spatial Distribution of Clonal Complexes of Streptococcus pneumoniae Isolates Resistant to Multiple Classes of Antibiotics in Belgium, 1997 to 2004

ABSTRACT We performed multilocus sequence typing on 203 invasive disease isolates of Streptococcus pneumoniae to assess the clonal compositions of isolates from two provinces in Belgium and to determine the relationship between clones and antibiotic nonsusceptibility, particularly nonsusceptibility to two or more classes of antibiotics. The frequency of multiclass nonsusceptibility (MCNS) was higher in the province of West Flanders (38%) than in Limburg (21%). This difference was largely attributable to five clonal complexes (CC156, CC81, CC143, CC193, and CC1848), which contained high proportions of isolates with MCNS (>47%) and which were circulating at higher frequencies in West Flanders. The S. pneumoniae population changed over time, as CC156 and CC81 declined in frequency from 1997 to 1999 to 2001 to 2004. Over the same time period, the frequency of pneumococcal conjugate vaccine 7 (PCV7) serotypes dropped from 69% to 41%. In contrast, the nonvaccine serotype 19A increased in frequency from 2.1% to 6.6%. None of these changes can be attributed to PCV7 vaccine, as it was not in use in Belgium during the time period studied. There was evidence that MCNS clones flowed from West Flanders to Limburg.

Semi-automated risk estimation using large databases: quinolones and clostridium difficile associated diarrhea†

The availability of large databases with person time information and appropriate statistical methods allow for relatively rapid pharmacovigilance analyses. A semi‐automated method was used to investigate the effect of fluoroquinolones on the incidence of C. difficile associated diarrhea (CDAD).