Lucia Stolzuoli

Antibiotic Usage and Risk of Colonization and Infection with Antibiotic-Resistant Bacteria: a Hospital Population-Based Study

ABSTRACT Accurate assessment of risk factors for nosocomial acquisition of colonization by antibiotic-resistant bacteria (ARB) is often confounded by scarce data on antibiotic use. A 12-month, nested, multicenter cohort study was conducted. Target ARB were methicillin (meticillin)-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and ciprofloxacin-resistant Pseudomonas aeruginosa (CR-PA). Nares and rectal swabs were obtained before and after starting antibiotics. Pulsed-field gel electrophoresis was done to define genetic relatedness of the strains. Primary outcomes were (i) the mean time, in days, for acquisition of target ARB colonization in patients previously not colonized; (ii) the rate of acquisition per 1,000 antibiotic-days according to different classes of antibiotics; (iii) the rate of infection caused by the same bacteria as those previously isolated in screening samples; and (iv) the risk factors for ARB acquisition. In total, 6,245 swabs from 864 inpatients were processed. The rate of acquisition was 3%, 2%, and 1% for MRSA, VRE, and CR-PA, respectively. The rate of acquisition of ARB per 1,000 antibiotic-days was 14 for carbapenems, 9 for glycopeptides, and 6 for broad-spectrum cephalosporins and quinolones. The highest rates of acquisition were observed for carbapenems in dialyzed and diabetic patients. Four risk factors were independently associated with acquisition of target ARB: use of carbapenems, age of >70 years, hospitalization for >16 days, and human immunodeficiency virus infection. During the 30-day follow-up, 4 among 42 patients newly colonized by ARB (9%) suffered from an infection due to the same bacteria as those isolated in a previous screening sample. Colonizing and infecting strains from single patients were genotypically identical. Identifying ARB colonization early during antibiotic therapy could target a high-risk hospitalized population that may benefit from intervention to decrease the risk of subsequent nosocomial infections.

Erythromycin Resistance in Streptococcus pyogenes and Macrolide Consumption in a Central Italian Region

AbstractBackground:The study investigated macrolide resistance in Streptococcus pyogenes in a central Italian area from 2001 to 2006 and the possible correlation between antibiotic consumption and fluctuations of resistance percentages.Materials and Methods:Macrolide and lincosamide susceptibility of 1,419 S. pyogenes isolates was tested by Kirby Bauer method. Macrolide consumption was valuated as defined daily dose/1,000 inhabitants per day (DID), according to the World Health Organization anatomic therapeutic chemical classification. Spearman’s correlation coefficient was used to assess the association between resistance and use of (1) all macrolides pooled, (2) once daily, (3) twice daily, and (4) three times daily dosage regimens.Results:In total, 320 strains (22.6%) were erythromycinresistant, 11.4% with the M phenotype and 11.2% with the MLS phenotype. There was a significant decrease in erythromycin resistance during the study period—from 28.1% in 2001 to 15.6% in 2006 (p < 0.01). No significant correlation was found between erythromycin resistance and local overall macrolide consumption, neither during the same year nor during the previous year. In contrast, a significant correlation was found between resistance rates and oncedaily macrolide use during the preceding 6 months in Siena r = 0.747, p = 0.008).Conclusion:The known greater selective effect of longacting agents could establish a pressure outcome, resulting in a specific local epidemiology during a relatively short time gap.

Pneumococcal disease in a paediatric population in a hospital of central Italy : A clinical and microbiological case series from 1992 to 2006

OBJECTIVES Streptococcus pneumoniae is frequently isolated from carrier children, but it also causes localized and invasive diseases. Increasing incidence of chemoresistance can affect the efficacy of empiric therapy and it motivates interest in primary prophylaxis. The study aims to investigate clinical and microbiological features of paediatric pneumococcal infections in an Italian province. METHODS Retrospective clinical analysis of 640 children, hospitalized from 1992 to 2006 with one culture positive for S. pneumoniae, was performed. Chemosusceptibility tests and serotyping were carried out on isolates; statistical analysis was applied to compare variables. RESULTS Overall, 47.8% were carriers, 49% and 3.2% had, respectively, a localized or invasive disease; S. pneumoniae aetiology accounted for 25% of meningitis and 16% of sepsis. On the total isolates, 10.2% were penicillin non-susceptible, 35.15% were erythromycin resistant, with increasing rates over years. Prevalent invasive serotypes were 1 (38.1%) and 7F (9.5%). CONCLUSIONS The study sustains pneumococcal disease relevance in children, on the strength of a 15 year observation. Long time period can represent a limit due to population characteristics changing; a selection bias could also be present due to hospitalized only patient analysis. However, we documented variable evolution of chemoresistance and a peculiar serotype spreading, offering microbiological basis for an appropriate clinical approach.

Clindamycin-resistant Streptococcus pneumoniae.

To the Editor: Antimicrobial medications classified as macrolides (e.g., erythromycin) and lincosamides (e.g., clindamycin) show strong activity against streptococci and are commonly used to treat community-acquired infections caused by Streptococcus pneumoniae. Moreover, these drugs are the recommended alternatives for patients who cannot tolerate β-lactams. Two main macrolide-resistant S. pneumoniae phenotypes have been reported (1). The first has a high level of resistance to all macrolides, lincosamides, ketolides, and streptogramins B due to ribosomal dimethylation, 23S rRNA mutations, or ribosomal protein mutations (MLSB, MSB, ML, MKSB, and K phenotypes). The second is characterized by a low-level resistance (e.g., MIC 2–4 mg/L) to only 14- and 15-member ring macrolides (M phenotype) because of mef gene–mediated active drug efflux mechanism. In January 2005, an erythromycin-susceptible but clindamycin-resistant pneumococcal strain was obtained from a conjunctival swab of a 10-month-old female outpatient attending the daycare center of the Clinic and Laboratory of Infectious Diseases, Siena University, Siena, Italy. To our knowledge, such a phenotype has not been reported in the international literature for S. pneumoniae, although a similar phenotype of Streptococcus agalactiae was described by Malbruny et al. (2). The S. pneumoniae isolate was identified by standard procedures (3) and confirmed by PCR for the common capsule gene cpsA (4). Serotyping, performed by Quellung reaction, showed a 35F serotype. Susceptibility testing was carried out by disk diffusion and confirmed with E-test according to Clinical and Laboratory Standards Institute standards (5,6) for penicillin, ceftriaxone, ciprofloxacin, erythromycin, clindamycin, linezolid, and quinupristin-dalfopristin. For telithromycin, because an E-test strip was unavailable, a microbroth diluiton method was used. The strain was susceptible to ceftriaxone (MIC 0.125 mg/L), ciprofloxacin (MIC 0.125 mg/L), erythromycin (MIC 0.125 mg/L), linezolid (MIC 1.5 mg/L), quinupristin/dalfopristin (MIC 0.5 mg/L), and telithromycin (MIC <0.0035 mg/L); it was not susceptible to penicillin (MIC 0.125 mg/L) and was resistant to clindamycin (MIC 1 mg/L). A triple disk–diffusion test with erythromycin, clindamycin, and josamycin was performed to test resistance inducibility. No inducible pattern was shown. To understand the possible resistance mechanism, MICs for 2 lincosamides (clindamycin and lincomycin) were determined by using a microbroth dilution method in the presence and absence of 10 mg/L of the efflux pump inhibitor reserpine (Sigma Chemicals, St Louis, MO, USA), as described (7); S. pneumoniae ATCC 49619 and S. mitis 21A29 (mefE+) were used as controls (8). The MICs remained unchanged in the presence of reserpine: 1 mg/L for clindamycin and 4 mg/L for lincomycin. The strain was screened for ermTR, ermB or mefA, and mefE determinants as described (8,9). All PCR controls gave the expected results. No PCR product was obtained for the studied isolate. Preliminary data did not show classic macrolide resistance determinants for S. pneumoniae. Low-level lincosamide resistance suggests the presence of some efflux mechanism, even if no inhibition by reserpine was observed. Moreover, no mutations of ribosomal proteins and of known binding sites for lincosamides in rRNA (1) were shown by sequencing of L22, L4, and 23S rRNA domain II and V genes with primers described by Canu et al. (10). Although these findings are preliminary and the molecular basis for resistance is the subject of ongoing investigation, the identification of this S. pneumoniae phenotype may affect clinical management of pneumococcal infections, especially in the treatment of patients intolerant of β-lactams.

Serotype distribution, clonality and antimicrobial resistance of invasive pneumococcal isolates in a central Italian region: implications for vaccine strategies

Streptococcus pneumoniae is a leading cause of serious invasive infections with high morbidity and mortality rates. Current primary prophylaxis is based on vaccines containing capsular polysaccharides of most common invasive serotypes. However, serotype distribution differs by age and in different geographic areas [3]; Italian data about capsular type distribution, antibiotic resistance and clonality of invasive isolates are particularly scanty and no recent data are available from central Italy. The aim of this study was to characterize 26 S. pneumoniae invasive isolates from paediatric patients, collected during 1992–2005 in the Siena province, determining their antimicrobial susceptibility, serotypes and clonality by pulsed-field gel electrophoresis (PFGE). All subjects were admitted to the Infectious Diseases Clinic of Siena University, the only reference unit for paediatric infectious diseases in Siena province. Susceptibility tests were performed by disk-diffusion method on Mueller Hinton Agar+5% sheep blood, according to the Clinical and Laboratory Standards Institute (CLSI), against erythromycin, clindamycin, josamycin, rifampin, chloramphenicol, ofloxacin and teicoplanin. Penicillin and ceftriaxone minimal inhibitory concentrations (MICs) were determined by Etest. Pneumococci were serotyped by the quellung reaction at Streptococcal Reference Unit of Respiratory and Systemic Infection Laboratory, London. PFGE of SmaI restriction fragments was performed as described previously [4] using a CHEF-DRIII apparatus. Strain relatedness was analysed according to consensus criteria [6]. Patients and isolates characteristic are reported in Table 1. Twenty-three isolates were susceptible to all tested antibiotics. Only one was intermediate resistant to penicillin (MIC 0.25 mg/l). Three strains showed erythromycin resistance. Only one strain was resistant to chloramphenicol. No resistance was observed against ceftriaxone, rifampin, ofloxacin and teicoplanin. No invasive S. pneumoniae were isolated in 1996, 1997, 2003 and 2005. Twelve different serotypes were observed; the most prevalent were 1 (9 isolates), 6A and 14 (3 respectively). Nine of 26 (34.6%) strains belonged to serotypes included in heptavalent protein-conjugate pneumococcal vaccine (PCV7); 22 strains (84.6%) belonged to serotypes included in 23-valent polysaccharide pneumococcal vaccine (PPV23). PFGE patterns were classified into 19 types (Table 1). Pneumococci of the most common serotype 1 were Eur J Pediatr (2007) 166:875–877 DOI 10.1007/s00431-006-0318-6