Penicillin-resistant S. Pneumoniae Research Articles

Serotype, antibiotic susceptibility and whole-genome characterization of Streptococcus pneumoniae in all age groups living in Southwest China during 2018-2022.

Streptococcus pneumoniae is a common pathogen that colonizes the human upper respiratory tract, causing high morbidity and mortality worldwide. This study aimed to investigate the prevalence status of S. pneumoniae isolated from patients of all ages in Southwest China, including serotype, antibiotic susceptibility and other molecular characteristics, to provide a basis for clinical antibiotic usage and vaccine development. This study was conducted from January 2018 to March 2022 at West China Hospital, West China Second University Hospital, First People's Hospital of Longquanyi District (West China Longquan Hospital), Meishan Women and Children's Hospital (Alliance Hospital of West China Second University Hospital) and Chengdu Jinjiang Hospital for Women and Children Health. Demographic and clinical characteristics of 263 pneumococcal disease (PD) all-age patients were collected and analyzed. The serotypes, sequence types (STs), and antibiotic resistance of the strains were determined by next-generation sequencing, sequence analysis and the microdilution broth method. The most common pneumococcal serotypes were 19F (17.87%), 19A (11.41%), 3 (8.75%), 23F (6.46%) and 6A (5.70%). Coverage rates for PCV10, PCV13, PCV15, PCV20 and PCV24 were 36.12, 61.98, 61.98, 63.12 and 64.26%, respectively. Prevalent STs were ST271 (12.55%), ST320 (11.79%), ST90 (4.18%), ST876 (4.18%) and ST11972 (3.42%). Penicillin-resistant S. pneumoniae (PRSP) accounted for 82.35 and 1.22% of meningitis and nonmeningitis PD cases, respectively. Resistance genes msrD (32.7%), mefA (32.7%), ermB (95.8%), tetM (97.3%) and catTC (7.6%) were found among 263 isolates. Most isolates showed high resistance to erythromycin (96.96%) and tetracycline (79.85%), with more than half being resistant to SXT (58.94%). A few isolates were resistant to AMX (9.89%), CTX (11.03%), MEN (9.13%), OFX (1.14%), LVX (1.14%) and MXF (0.38%). All isolates were susceptible to vancomycin and linezolid. Our study provides reliable information, including the prevalence, molecular characterization and antimicrobial resistance of S. pneumoniae isolates causing pneumococcal diseases in Southwest China. The findings contribute to informed and clinical policy decisions for prevention and treatment.

Ceftobiprole medocaril for the treatment of pneumonia

ABSTRACT Introduction Ceftobiprole, a fifth-generation cephalosporin, exhibits a broad-spectrum activity against common pathogens causing pneumonia, including multidrug-resistant organisms (MDROs), such as penicillin-resistant S. pneumoniae (PRSP) and methicillin-resistant Staphylococcus aureus (MRSA) and non-extended-spectrum β -lactamase (non-ESBL) producing Enterobacterales strains. Therefore, ceftobiprole should be considered as a potential alternative for the empirical treatment of pneumonia in patients with high risk for MDROs. Area covered In this review, we discussed the role of ceftobiprole in the treatment of patients with pneumonia. Expert opinion Ceftobiprole has several advantages in the treatment of pneumonia. First, ceftobiprole exerts its bactericidal activity by inhibiting transpeptidases, especially showing strong affinities to penicillin-binding protein (PBP) 2a, PBP2× and PBP3. Second, its plasma protein binding is minimal, allowing it to penetrate lung tissue and achieve high concentrations in epithelial lung fluid. Third, ceftobiprole exhibits potent in vitro activity against a wide range of susceptible pathogens, including S. aureus, S. pneumoniae, Viridans streptococci, H. influenzae, M. catarrhalis, Enterobacterales, and particularly, MRSA and P. aeruginosa. Finally, several randomized controlled trials have demonstrated the clinical efficacy and safety of ceftobiprole in the treatment of pediatric and adult patients with community-acquired pneumonia and hospital-acquired pneumonia (excluding ventilator-associated pneumonia).

Combining the In Silico and In Vitro Assays to Identify Strobilanthes cusia Kuntze Bioactives against Penicillin-Resistant Streptococcus pneumoniae.

Leaves of Strobilanthes cusia Kuntze (S. cusia) are a widely used alexipharmic Traditional Chinese Medicine (TCM) in southern China for the prevention of cold and respiratory tract infectious diseases. One of the most common bacterial pathogens in the respiratory tract is the gram-positive bacterium Streptococcus pneumoniae. The antibiotic resistance of colonized S. pneumoniae makes it a more serious threat to public health. In this study, the leaves of S. cusia were found to perform antibacterial effects on the penicillin-resistant S. pneumoniae (PRSP). Confocal assay and Transmission Electron Microscopy (TEM) monitored the diminished cell wall integrity and capsule thickness of the PRSP with treatment. The following comparative proteomics analysis revealed that the glycometabolism-related pathways were enriched for the differentially expressed proteins between the samples with treatment and the control. To further delve into the specific single effective compound, the bio-active contents of leaves of S. cusia were analyzed by UPLC-UV-ESI-Q-TOF/MS, and 23 compounds were isolated for anti-PRSP screening. Among them, Tryptanthrin demonstrated the most promising effect, and it possibly inhibited the N-glycan degradation proteins, as suggested by reverse docking analysis in silico and further experimental verification by the surface plasmon resonance assay (SPR). Our study provided a research foundation for applications of the leaves of S. cusia as a TCM, and supplied a bio-active compound Tryptanthrin as a candidate drug skeleton for infectious diseases caused by the PRSP.

Molecular Characterization of Penicillin-Binding Protein2x, 2b and 1a of Streptococcus pneumoniae Causing Invasive Pneumococcal Diseases in China: A Multicenter Study.

Streptococcus pneumoniae is a common human pathogen that can cause severe invasive pneumococcal diseases (IPDs). Penicillin-binding proteins (PBPs) are the targets for β-lactam antibiotics (BLAs), which are the common empirical drugs for treatment of pneumococcal infection. This study investigated the serotype distribution and antibiotic resistance patterns of S. pneumoniae strains causing IPD in China, including exploring the association between penicillin (PEN) susceptibility and PBPs variations. A total of 300 invasive S. pneumoniae isolates were collected from 27 teaching hospitals in China (2010-2015). Serotypes were determined by Quellung reaction. Serotypes 23F and 19F were the commonest serotypes in isolates from cerebrospinal fluid (CSF), whilst serotypes 19A and 23F were most commonly seen in non-CSF specimens. Among the 300 invasive S. pneumoniae strains, only one strain (serotype 6A, MIC = 0.25 μg/ml) with PEN MIC value ≤ 0.25 μg/ml did not have any substitutions in the PBPs active sites. All the strains with PEN MIC value ≥ 0.5 μg/ml had different substitutions within PBPs active sites. Substitutions in PBP2b and PBP2x active sites were common in low-level penicillin-resistant S. pneumoniae (PRSP) strains (MIC = 0.5 μg/ml), with or without PBP1a substitution, while all strains with PEN MIC ≥ 1 μg/ml had substitutions in PBP1a active sites, accompanied by PBP2b and PBP2x active site substitutions. Based on the three PBPs substitution combinations, a high degree of diversity was observed amongst the isolates. This study provides some new insights for understanding the serology and antibiotic resistance dynamics of S. pneumoniae causing IPD in China. However, further genomic studies are needed to facilitate a comprehensive understanding of antibiotic resistance mechanisms of S. pneumoniae.

Penicillin- and third-generation cephalosporin-resistant strains of Streptococcus pneumoniae meningitis: Case report and literature review

BackgroundTreatment of patients with penicillin-resistant S. pneumoniae (PRSP) is complicated because of the relatively poor blood-brain barrier penetration of effective antimicrobials. Our case: A previously healthy 70-year-old woman, a traveler from China to Japan, was admitted to our hospital with fever and loss of consciousness. She has no history of pneumococcal vaccination. She was diagnosed with bacterial meningitis due to penicillin-and third-generation cephalosporin-resistant strains of S. pneumoniae. The patient was successfully treated with a combination therapy of vancomycin (VCM) and levofloxacin (LVFX) and recovered without any neurological sequelae. As the treatment of penicillin-and third-generation cephalosporin-resistant strains of S. pneumoniae meningitis remains unclear, we conducted a review of the reported cases of meningitis caused by penicillin- and cephalosporin-resistant S. pneumoniae. MethodWe performed a search using the keywords “penicillin-resistant Streptococcus pneumoniae,” “meningitis,” and “pneumococcal meningitis”. We searched the electronic databases PubMed, Embase, and Ichushi from their inception to March 2020. Subsequently, two authors independently reviewed the resulting database records, retrieved full texts for eligibility assessment, and extracted data from these cases. ResultWe identified 18 papers describing thirty-five cases of penicillin- and cephalosporin-resistant S. pneumoniae meningitis including our case. The patient's characteristics were; median age: 50 years, men:50%, 85% of cases received combination regimens of antibiotics: Ceftroriaxone (CTRX) plus VCM (20 cases), CTRX plus VCM plus rifampicin (RFP) (two cases), CTRX plus linezolid (one case), fluoroquinolones (two cases), carbapenems (six cases), Thirty-five percent received steroids. Twenty-four percent of patients died. Twenty-six percent of patients complicated neurological sequalae. ConclusionCombination therapy including VCM plus LVFX could be a treatment option.

Increase in Penicillin and multidrug resistance in Streptococcus pneumoniae (1993-2016): Report from a tertiary care hospital laboratory, Pakistan.

To determine the trend of resistance to antimicrobials in Streptococcus pneumoniae infections, and the impact of new Clinical and Laboratory Standards Institute guidelines on 1211 among meningeal isolates. The descriptive observational retrospective study was conducted at the Aga Khan University Hospital laboratory in Karachi, and comprised Streptococcus pneumoniae isolation and antimicrobial susceptibility data over a period of 24 years, from 1993 to 2016, which was compared in terms of pre-2008 and post-2008 data, which was analysed using SPSS 19. Of the 7415 non-duplicate isolates identified, 4700(63.4%) were from male patients and 2,715(36.6%) were from female patients. The overall mean age of the patients was 38±27 years. Penicillin resistance in non-meningeal isolates during the two periods was not significantly different (p>0.05), but a significant rise in penicillin resistance in meningeal isolates was observed in the second period (p<0.05). High resistance rates were observed for co-trimoxazole, tetracycline and erythromycin, and an increased trend of multi-drug resistant strains was also noted from 1999 {n=35/317(11%)} to 2016 {n=110/314 (36%)}. The emergence of multi-drug resistant strains was evident. The spike in penicillin-resistant Streptococcus pneumoniae in meningeal isolates may have been due to the revised guidelines by the Clinical and Laboratory Standards Institute.

Antimicrobial Activity of Omadacycline Tested against Clinical Bacterial Isolates from Hospitals in Mainland China, Hong Kong, and Taiwan: Results from the SENTRY Antimicrobial Surveillance Program (2013 to 2016).

Omadacycline is a derivative of minocycline and the first agent of the aminomethylcycline class. A total of 3,282 organisms (1 per patient) were consecutively collected from patients hospitalized in China (including Hong Kong) and Taiwan. Susceptibility testing was performed by broth microdilution methods in a central laboratory (JMI Laboratories). The collection included Gram-positive and Gram-negative organisms from patients with pneumonia, bloodstream, skin, community-acquired respiratory, and other infections. Omadacycline was very potent against Staphylococcus aureus (n = 689; MIC50/90, 0.12/0.25 mg/liter), including methicillin-resistant Staphylococcus aureus (MRSA; n = 299; MIC50/90, 0.12/0.5 mg/liter), and had similar activity across geographic regions. Omadacycline was very active against Streptococcus pneumoniae (highest MIC, 0.25 mg/liter), β-hemolytic streptococci (highest MIC, 1 mg/liter), viridans group streptococci (highest MIC, 0.25 mg/liter), and Enterococcus spp. (highest MIC, 0.5 mg/liter) from all geographic regions. Overall, 53.8% of S. pneumoniae isolates were penicillin resistant (penicillin MIC, ≥2 mg/liter) and 10.7% of enterococci (21.2% among E. faecium isolates) were vancomycin resistant. Omadacycline was active against Haemophilus influenzae (MIC50/90, 0.5/1 mg/liter) regardless of β-lactamase production and was active against Moraxella catarrhalis (MIC50/90, ≤0.12/0.25 mg/liter). Against Enterobacteriaceae, omadacycline was most active against Escherichia coli (MIC50/90, 1/2 mg/liter), Klebsiella oxytoca (MIC50/90, 1/4 mg/liter), and Enterobacter cloacae (MIC50/90, 2/4 mg/liter). Omadacycline had potent in vitro activity against Gram-positive and Gram-negative pathogens isolated from China and Taiwan and retained activity against problem pathogens, such as MRSA, vancomycin-resistant enterococci (VRE), penicillin-resistant S. pneumoniae (PRSPN), and extended-spectrum β-lactamase-producing E. coli The observed MIC profile in Chinese isolates was very similar to that seen in the U.S. and European surveillance studies.

Serotype distribution of Streptococcus pneumoniae isolated from adult respiratory tract infections in nationwide Japanese surveillances from 2006 to 2014.

Reports on the efficacy of pneumococcal conjugate vaccines (PCVs) have been received from many countries. However, in countries where the 7-valent PCV (PCV7) and 13-valent PCV (PCV13) were introduced, overall coverage of the serotypes by the vaccine gradually decreased due to pneumococcal serotype replacement. The aim of this study is to assess the distribution of pneumococcal serotypes and to also provide basic data on adult respiratory infection in Japan. We analyzed 1086 Streptococcus pneumoniae strains that had been isolated from respiratory tract infection specimens in adult patients from 2006 to 2014. Capsular typing was performed by the Quellung reaction and multiplex PCR. Among all 1086 strains, serotype 3 was the most common and was identified in 160 strains (14.7%), followed by serotypes 19F, 6B, 19A and 23F. From 2006-10 to 2012-14, the coverage rate of PCV7 tended to gradually decrease. Particularly, serotypes 6B and 19F of penicillin non-susceptible strains decreased. On the other hand, serotypes 19A and 15A of penicillin non-susceptible strains increased. However, coverage by PCV13 of penicillin-resistant S.pneumoniae (PRSP) (penicillin G minimum inhibitory concentration ≥2μg/mL) remained high (88.7% [2006-10], 88.0% [2012-14]). In Japan, PCV13 vaccination of adults became available from June 2014. Our study demonstrated that most PRSP (88.0%) still remain covered by PCV13. At present, the introduction of PCV13 in adult clinical practice seems to be highly significant. However, there is a possibility that the distribution has been changing, and careful screening should be continued in the future.

Bacteriological Analysis of Pneumococcus Detected from the Sputum of Hospitalized Children

7-valent pneumococcal conjugate vaccine (PCV7) has been included in the routine immunization schedule since April 2013 in Japan. Serotype replacement - a phenomenon by which serotypes are replaced by non-vaccine serotypes after vaccine introduction - has been reported in invasive pneumococcal disease (IPD). Pneumococcus in sputum samples is one of the major causes of bronchopulmonary infection in children. We tried to verify whether serotype replacement of Pneumococcus occurs in sputum samples in a similar manner as in IPD. From August 2014 to September 2015, we performed antimicrobial susceptibility testing and serotyping of Streptococcus pneumoniae from sputum samples and investigated the history of PCV from hospitalized children with S. pneumoniae bronchopulmonary infection. From the results of our investigation, 80.3% of children have received PCV at least once. Serotypes of Pneumococcus were determined in 92.4% of tested strains and PCV13 strains accounted for only 9.8%. Major isolated serotypes were 15A (21.3%), 35B (19.7%), and 6C (13.1%). Those were not included in PCV13, i.e. serotype replacement occurs in bronchopulmonary infection just as in IPD. The results of antimicrobial susceptibility testing for Penicillin G indicated that penicillin-resistant S. pneumoniae (PRSP) accounted for 4.5%, penicillin-intermediate resistant S. pneumoniae (PISP) accounted for 47.0% and penicillin-susceptible S. pneumoniae (PSSP) accounted for 48.5%. When examining the drug susceptibility by serotypes, 15A, 19A, 23A and 35B showed a high percentage of non-susceptibility. This means there is a difference in the resistant trend by serotypes. In our study, it became clear that verifying of the serotypes of Pneumococcus in sputum is meaningful and surveillance of serotypes is important for evaluation of vaccination as IPD.

Molecular characteristics of penicillin-binding protein 2b, 2x and 1a sequences in Streptococcus pneumoniae isolates causing invasive diseases among children in Northeast China.

Streptococcus pneumoniae is one of the common pathogens causing severe invasive infections in children. This study aimed to investigate the serotype distribution and variations of penicillin-binding proteins (PBPs) 2b, 2x and 1a in S. pneumoniae isolates causing invasive diseases in Northeast China. A total of 256 strains were isolated from children with invasive pneumococcal disease (IPD) from January 2000 to October 2014. All strains were serotyped and determined for antibiotic resistance. The amplicons of penicillin-binding domains in pbp1a, pbp2b and pbp2x genes were sequenced for variation identification. The most prevalent serotypes of isolates in IPD children were 19A, 14, 19F, 23F and 6B. 19A and 19F were the most frequent serotypes of penicillin-resistant S. pneumoniae (PRSP), which present with high resistance to amoxicillin, cefotaxime, ceftriaxone and meropenem. The numbers of amino acid substitutions of penicillin-non-susceptible S. pneumoniae (PNSP) isolates were higher than those of penicillin-sensitive S. pneumoniae isolates in all the PBP genes (p < 0.01). The patterns of amino acid mutation in PBP2b, PBP2x and PBP1a were unique and different from those of other countries. All of the serotype 19A and 19F PRSP isolates carried 25 amino acid mutations, including Ala618 → Gly between positions 560 and 675 in PBP2b and Thr338 → Ala substitutions in PBP2x. The amino acid alterations in PBP2b, PBP2x and PBP1a from S. pneumoniae were closely associated with resistance to β-lactam antibiotics. This study provides new data for further monitoring of genetic changes related to the emergence and spread of resistance to β-lactam antibiotics in China.

Nationwide survey of Streptococcus pneumoniae drug resistance in the pediatric field in Japan.

Streptococcus pneumoniae is a major causative pathogen of pneumonia in children. The Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease conducted a nationwide surveillance of S. pneumoniae in 2000-2001, 2004, 2007, 2010 and 2012, and investigated changes in drug resistance of S. pneumoniae. All strains of S. pneumoniae were isolated from clinical specimens collected from pediatric patients. The minimun inhibitory concentration was measured and the strains were classified according to the Clinical Laboratory Standards Institute criteria. The isolation rates of penicillin-intermediate resistant S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were compared based on seven patient factors. Logistic regression analysis was also performed. The sum of the isolation rates for PISP and PRSP for each period was 64.6%, 67.0%, 56.2%, 76.9% and 49.5%, respectively. Among the patient factors, age category 1 (<3 years, ≥3 years), age category 2 (infant, toddler and preschooler, schoolchild), siblings (absence, presence), and pre-treatment with antimicrobial agents (absence, presence) were associated with significant differences in the isolation rate of PISP + PRSP. An interaction was observed between pre-treatment with antimicrobial agents and schoolchild, and the isolation rate of PISP + PRSP was higher in patients with both pre-treatment with antimicrobial agents and schoolchild. Although some changes were observed in the rate of resistance of S. pneumoniae, an increasing trend was not observed. Both pre-treatment with antimicrobial agents and age were associated with resistance, and an interaction was observed between pre-treatment with antimicrobial agents and schoolchild.

Molecular chaperones (TrxA, SUMO, Intein, and GST) mediating expression, purification, and antimicrobial activity assays of plectasin in Escherichia coli.

Plectasin (PS) is the first defensin to be isolated from a fungus, the saprophytic ascomycete Pseudoplectania nigrella, and active against Streptococcus pneumoniae and S. aureus, including antibiotic-resistant pathogens. To establish a bacterium-based production system, we compared the efficiency of four molecular chaperones and corresponding cleavage to the expression and purification of plectasin. The results showed that the yield of plectasin combined with thioredoxin A (TrxA) and small ubiquitin-related modifier (SUMO) was at a higher level (0.0356 and 0.0358 g L(-1), respectively) than that with intein (0.0238 g L(-1)) and glutathione-S-transferase (GST) (0.0243 g L(-1)). TrxA-plectasin, SUMO-plectasin, and 2-plectasin were cleaved at the correct site and purified, but their considerable amount was not cleaved and remained as a fusion peptide. The antimicrobial activity of plectasin cleaved from SUMO--plectasin against methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant S. pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE)--was stronger than ampicillin (Amp) for the same amount of substance (P ≤ 0.05). This is the first study to complete and compare the effect of different molecular chaperones and corresponding cleavage with the expression and purification of plectasin in the Escherichia coli expression system, which laid the foundation for future research and may develop the application and production of plectasin.

Serotype distribution and susceptibility to penicillin and erythromycin among noninvasive or colonization isolates of Streptococcus pneumoniae in northern Japan: a cross-sectional study in the pre-PCV7 routine immunization period.

Distribution of serotypes, prevalence of resistance to penicillin and/or erythromycin (EM), and its genetic traits were analyzed for a total of 1,061 noninvasive or colonization isolates of Streptococcus pneumoniae (998 and 61 isolates from children and adults, respectively) in Hokkaido, northern main island of Japan, in the year 2011, the pre-PCV7 routine immunization period. Serotype deduction was performed by sequential multiplex polymerase chain reaction (PCR), employing mutagenic PCR-restriction fragment length polymorphism for discrimination of 6A/C and 6B/D. Unaltered three PBP genes and macrolide resistance genes erm(B) and mef(A/E) were detected by multiplex PCR. Among isolates from children, 25 serotypes, including the prevalent types 6B (17.5%), 19F (15.6%), 23F (12.2%), and 6C (11.6%), were identified, revealing the PCV7 and PCV13 coverage rates as 48.2% and 60.3%, respectively, while serotype 3 was the most frequent (19.0%) among isolates from adults. Most of the pediatric isolates (96.8%) exhibited resistance to EM (minimum inhibitory concentration [MIC], ≥1 μg/ml), with a higher prevalence of erm(B) (67.2%) than mef(A/E) (39.7%). erm(B) was associated with high-level EM resistance (MIC, ≥128 μg/ml) and distributed at high detection rates to major serotypes 23F (85.2%) and 6B (85.1%), as well as minor serotypes 3, 10A, 14, 15B, 15C, 19A, and 23A (>90%). While penicillin-resistant S. pneumoniae (PRSP) (penicillin G-MIC, 2-3 μg/ml) was detected in 7.8% of isolates from children, the most common PBP gene genotype was gPRSP (three altered genes pbp1a, 2x, and 2b; 38.3%), which was detected at higher rates (>60%) in the dominant serotypes 23F, 6B, and 19F, and minor serotypes 6D and 15A. Dominant serotypes in the S. pneumoniae isolates were generally similar to those reported for invasive strains, despite lower coverage rates by PCV7/13. The importance of further surveillance on incidence and drug resistance in the post-PCV7 period was suggested for non-PCV7/13 serotypes 6C, 6D, 10A, 15A, 15B, 15C, 23A, and 35B.

新潟県長岡地区の基幹病院における肺炎球菌, インフルエンザ菌, 緑膿菌の検出状況と抗生物質に対する感受性の検討 (3年間の年次推移)

We measured MICs of various antimicrobial agents against Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa isolated in the Nagaoka district of Niigata Prefecture in 2000 (March-May), 2001 (January-May), and 2002 (March-May). S. pneumoniae: Fifty-six strains were isolated in 2000, 119 strains in 2001, and 88 strains in 2002. In 2000, 2001, and 2002, 24 strains (42.9%), 58 strains (48.7%), and 40 strains (45.5%), respectively, were penicillin-intermediate S. pneumoniae (PISP), and 4 strains (7.1%), 12 strains (10.1%), and 7 strains (8.0%), respectively, were penicillin-resistant S. pneumoniae (PRSP). Carbapenems had the most excellent antimicrobial activity, followed by penicillin G, against penicillin-susceptible S. pneumoniae (PSSP), PISP, and PRSP. H. influenzae: Seventy-six strains were isolated in 2000, 154 strains in 2001, and 91 strains in 2002. In 2000, 2001, and 2002, 6 strains (7.9%), 8 strains (5.2%), and 7 strains (7.7%), respectively, were beta-lactamase-producing ampicillin (ABPC)-resistant strains (MIC > or = 2 micrograms/ml), showing no increase, and 14 strains (18.4%), 70 strains (45.5%), and 31 strains (34.1%), respectively, were beta-lactamase-non-producing ABPC-resistant strains (MIC > or = 2 micrograms/ml), showing a slight increase. Ceftriaxon, meropenem (MEPM), and levofloxacin had excellent antimicrobial activity against these resistant strains. P. aeruginosa: In 2000, 2001, and 2002, 135, 74, and 91 strains, respectively, were isolated, and 14 strains (10.4%), 17 strains (23.0%), and 24 strains (26.4%), respectively, were imipenem-resistant (MIC > or = 16 micrograms/ml), showing a slight increase. MEPM, biapenem, and ciprofloxacin had excellent antimicrobial activity against P. aeruginosa.

長野県下の基幹病院における肺炎球菌, インフルエンザ菌, 緑膿菌の分離状況と各薬剤感受性の検討

We determined the minimum inhibitory concentration (MIC) of various antimicrobial agents against 140 strains of Streptococcus pneumoniae, 131 strains of Haemophilus influenzae and 178 strains of Pseudomonas aeruginosa isolated from respiratory organs in 28 affiliated hospitals in Nagano prefecture between December 2002 and February 2003. The results of this report were as followed: 1. All 140 strains of S. pneumoniae were classified into 3 groups; penicillin-susceptible S. pneumoniae (PSSP) (47.1%), penicillin-intermediate S. pneumoniae (PISP) (43.6%) and penicillin-resistant S. pneumoniae (PRSP) (9.3%). 2. Carbapenems and glycopeptide (vancomycin) had highly potent antimicrobial activity against PISP and PRSP like PSSP. However, some of PISP or PRSP isolates were resistant to cephalosporins and a fluoroquinolone (levofloxacin). 3. All 131 strains ofH. Influenzae were also classified into three groups; ampicillin sensitive H. influenzae (73.3%), beta-lactamase producing ampicillin resistant H. influenzae (BLPAR) (8.4%) and beta-lactamase negative ampicillin resistant H. influenzae (BLNAR) (18.3%). 4. Carbapenems and a fluoroquinolone had highly potent antimicrobial activity against BLPAR and BLNAR. However, there were clear differences among 4 carbapenems for the antimicrobial activity. Ceftriaxone (CTRX) was the most active among cepharosporins in this study. 5. The rate of P. aeruginosa isolates resistant to carbapenems, a fluoroquinolone and aminoglycosides were about 11 to approximately 16%, 15% and 0.6 to approximately 8%, respectively. None of the strains was resistant to all 3 antimicrobial classes, but 3 strains were resistant to combination of 2 classes. 6. The MIC50 and MIC90 values of various antibiotics against S. pneumoniae, H. influenzae and P. aeruginosa were different in all 4 regions. In conclusion, the antimicrobial surveillance programs are important for guiding empiric therapy and for focusing interventional control of antimicrobial resistance in regions and hospitals.

Nationwide survey of the development of drug-resistant pathogens in the pediatric field in 2007 and 2010: drug sensitivity of Streptococcus pneumoniae in Japan (second report).

We previously conducted nationwide surveillance of Streptococcus pneumoniae in 2000–2001 (period 1) and 2004 (period 2) and reported the findings. Subsequent surveillance surveys conducted in 2007 (period 3) and 2010 (period 4) are now reported. Bacterial strains were clinically isolated from children with meningitis, sepsis, and respiratory tract infections at 27 hospitals participating in the Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. Twenty-one drugs were investigated for 283 isolated strains in period 3, and 24 drugs were investigated for 459 strains in period 4. In period 3, 43.8 % of strains were penicillin-susceptible S. pneumoniae (PSSP), 52.3 % were penicillin-intermediate S. pneumoniae (PISP), and 3.9 % were penicillin-resistant S. pneumoniae (PRSP). In period 4, the percentages were PSSP 23.1 %, PISP 49.9 %, and PRSP 27.0 %. The resistance rates were 56.2 % and 76.9 %, respectively. Drug sensitivity was best with panipenem, at a minimum inhibitory concentration (MIC)90 ≤0.063 μg/ml in period 3, and with tebipenem (MIC90 ≤ 0.063 μg/ml) in period 4. Patients’ background factors related to increased bacterial resistance were investigated, and significant differences were found depending on whether a child had siblings (P = 0.0056) or was a daycare center attendee (P = 0.0195) in period 3, and age category (P = 0.0256) in period 4. No factors were common to both periods 3 and 4. Pneumococcus is a major causative organism of pediatric infectious disease, and we plan to continue conducting surveillance and providing information in the future.

Determination of phenotypes and pneumococcal surface protein A family types of Streptococcus pneumoniae from Malaysian healthy children

There is limited information about pneumococcal carriage among healthy children in Malaysia. Therefore, this study was conducted to determine the prevalence rate, serotype distribution, susceptibility pattern, and pneumococcal surface protein A (PspA) family types of Streptococcus pneumoniae isolates in the nasal carriage of children 5 years old or younger in three day care centers in Kuala Lumpur, Malaysia. Nasal swabs were collected from 195 healthy children, age 5 years or younger, from June to December 2010. S pneumoniae was identified by phenotypic and genotypic methods. The serotyping was performed using Pneumotest kit (Statens Serum Institut, Copenhagen, Denmark) and the susceptibility pattern was determined by using the E-test method (AB Biodisk, Solna, Sweden). PspA family typing was done using polymerase chain reaction. S pneumoniae was found in the nasal carriage of 35.4% of children (69 of 195) and penicillin resistance was found in 23.2% (16 of 69). Among the 69 isolates, multidrug-resistant S pneumoniae (MDRSP) was present in 20.3%. All 16 penicillin-resistant S pneumoniae (PRSP) isolates were resistant to erythromycin and 14 PRSPs (87.5%) were resistant to co-trimoxazole. The six most common serotypes were 6A, 23F, 19A, 6B, 19F, and 15C, which were found in 87% of all isolates. Of the 69 isolates, 24.6% belonged to PspA family 1, 71.0% to PspA family 2, and 4.3% to PspA family 3. Twenty-eight of the isolates (40.6%) belonged to serotypes included in the pneumococcal polysaccharide vaccines (PCV) 7 and 10, whereas 48 (69.5%) were included in PCV13. The high rate of PRSP and MDRSP supports the need for continuing surveillance of pneumococcal carriage. The major PspA families were 1 and 2 (95.7%), thus making them suitable candidates for future vaccines.

Antimicrobial susceptibility of community-acquired respiratory tract pathogens isolated from adults in China during 2009 and 2010

To investigate the drug-resistance rates of community-acquired respiratory tract pathogens isolated from adults in China during 2009 and 2010. A total of 1793 strains (S. aureus 421, S. pneumoniae 420, K. pneumoniae 404, H. influenzae 313, other Streptococcus. spp 149, and M. catarrhalis 86) of non-duplicated community-acquired respiratory tract pathogens were isolated from 11 hospitals in 6 cities. The MIC values were determined by the broth microdilution method, and the production of β-lactamase was tested using a nitrocefin-based test. All of the S.aureus isolates were methicillin-sensitive (MSSA). Of the MSSA isolates, less than 1% (4/421) was resistant to β-lactamase inhibitor combinations, about 13.1% (55/421) and 9% (38/421) resistant to levofloxacin and moxifloxacin, and 57% (240/421), 53.2% (224/421), and 88.7% (373/421) resistant to azithromycin, clarithromycin, and penicillin, respectively. No S. aureus isolates resistant to vancomycin were detected in this study. Based on different criteria, the percentages of penicillin-sensitive S. pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) were 24.4% (102/420), 27.3% (115/420), 48.3% (203/420) (Oral) and 1.9% (8/420), 9% (38/420), 89.1% (374/420) (parenteral), respectively. The resistance rates of S. pneumonia to azithromycin, clarithromycin, cefaclor, cefuroxime, ceftriaxone and amoxicillin with clavulanic acid were 88.2% (370/420), 87.4% (367/420), 45.3% (190/420), 41.9% (176/420), 10.2% (43/420), and 5.2% (22/420), respectively. About 2.6% (11/420) and 0.2% (1/420) of S. pneumonia isolates were resistant to levofloxacin and moxifloxacin. More than 70% (104/149) of β-hemolytic streptococci isolates were resistant to azithromycin and clarithromycin, and about 10.1% (15/149) of isolates were resistant to levofloxacin. The resistance rates of K.pneumonia to most antibiotics were > 20% (81/404), and that of ceftazidime was lower than cefuroxime, cefaclor, and ceftriaxone. The mean prevalence value of ESBL producing K. pneumonia was 38.8% (157/404), with significantly regional variations. More than 90% of H. influenza and M. catarrhalis were susceptible to most antibiotics, with resistance rate of < 5% (16/313, H. influenza; 4/86, M. catarrhalis). The mean productions of β-lactamase in H. influenza and M. catarrhalis were 13.1% (41/313) and 91.7% (79/86), respectively. The percentage of PRSP increased significantly, and the resistance rates of community-acquired respiratory tract pathogens to common antibiotics such as macrolide and cephalosporins increased gradually. New fluoroquinolones such as moxifloxacin showed a high antimicrobial activity against most of the respiratory pathogens.

Nasopharyngeal Streptococcus pneumoniae carriage in Japanese children attending day-care centers

Objectives We conducted a prospective bacteriological survey to investigate antibiotic resistance-related genetic characteristics and the turnover of nasopharyngeal Streptococcus pneumoniae carriage in healthy children in day-care centers (DCCs). Methods A total of 363 nasopharyngeal mucus samples were collected from children aged 0 to 6 years attending two DCCs in the summer of 2004 ( n = 181) and the following winter ( n = 182). We obtained 157 S. pneumoniae isolates and analyzed them by antibiotic susceptibility testing, PCR assay for the penicillin-binding protein (PBP) genes and macrolide-resistance gene, and pulsed-field gel electrophoresis (PFGE). Results The overall carriage rate was 43.3% (157/363). The percentages of penicillin-intermediately resistant S. pneumoniae (PISP) strains, penicillin-resistant S. pneumoniae (PRSP) strains, erythromycin-intermediately resistant S. pneumoniae strains and erythromycin-resistant S. pneumoniae strains were 35.7% (56/157), 0.6% (1/157), 1.9% (3/157), and 69.4% (109/157), respectively. The percentages of S. pneumoniae strains with the pbp mutation(s) and mefA and/or ermB gene(s) were 92.4% (145/157) and 71.3% (112/157), respectively. Fifty strains with different PFGE patterns were obtained from among the 157 isolates. Thirteen strains were observed in both seasons, but only one of these strains was isolated from the same carrier. Twenty-one strains (42.0%) were isolated from two or more children, and 17 of these were each isolated from children attending the same DCC. Conclusions These results indicate the spread of S. pneumoniae, particularly those with antibiotic-resistance genes, and the vigorous genetic turnover and substantial horizontal transmission of this pathogen in healthy children attending DCCs in Japan.

Antibiotic Susceptibility of Respiratory Pathogens Recently Isolated in Italy: Focus on Cefditoren

The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community- acquired respiratory tract infections (CARTI). Cefditoren, out of all the beta-lactams studied, had the lowest MIC90 against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae, independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC90s were found for the macrolides (4 - 16 mg/L) and cefaclor (4 - 32 mg/L). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated miC90 values reduced (<75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC50/MIC90 values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC90s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC90s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some classes of antibiotics widely used as empiric therapy for CARTI, allows us to suggest that cefditoren might be included in the european guidelines as one of the first-choice antibiotics in the treatment of CARTI.