Geographical migration and fitness dynamics of Streptococcus pneumoniae.

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59-1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

Decoding the Penicillin Resistance of Streptococcus pneumoniae for Invasive and Noninvasive Infections.

This commentary explains the reasons for the extensive variations in pneumococcal penicillin resistance based on a literature review of pneumococcal penicillin-binding proteins, the pharmacodynamics and pharmacokinetics of beta-lactams, the risk factors associated with mortality, laboratory issues and challenges, including identification, susceptibility testing, and clinical reporting, and the management of invasive and noninvasive Streptococcus pneumoniae infections.

Therapy of Staphylococcus aureus bacteremia: Evidences and challenges / Tratamiento de la bacteriemia por Staphylococcus aureus: evidencias y retos

Staphylococcus aureus bacteremia (SAB) is still a daily challenge for clinicians. Despite all efforts, the associated mortality and morbidity has not significantly improved in the last 20 years. The available evidence suggests that adherence to some quality-of-care indicators with regard to clinical management is important in improving the outcome of patients, but it is lower than desired in many hospitals; as such, management of patients with SAB by infectious diseases specialists has been demonstrated to contribute in the reduction of the mortality rate of these patients. In this article, the most relevant clinical studies published over the last few years evaluating the efficacy and safety of alternative drugs for the treatment of SAB are reviewed. However, classic drugs are still used in a high proportion of patients because the promising results obtained from in vivo and in vivo studies with these alternative drugs have not translated as frequently as expected into evident superiority in clinical studies. Nevertheless, some data suggest that certain alternatives may offer advantages in specific situations. Overall, an individualised and expert approach is needed in order to decide the best treatment according to the source, severity, complications, patients' features and microbiological data

La bacteriemia por Staphylococcus aureus continúa siendo un reto diario para los clínicos. A pesar de todos los esfuerzos realizados, su mortalidad y morbilidad asociadas no han descendido de forma significativa en los últimos 20 años. Existe evidencia de que la adherencia a los indicadores de calidad para su manejo clínico es importante para mejorar el pronóstico de los pacientes, aunque su cumplimiento sigue siendo menor de lo deseado en muchos hospitales; en este sentido, la asistencia por especialistas en enfermedades infecciosas ha demostrado contribuir a reducir la mortalidad de estos pacientes. En este artículo se revisan los estudios clínicos más relevantes realizados en los últimos años con objeto de evaluar la eficacia y la seguridad de los fármacos alternativos a los clásicos. Sin embargo, estos siguen siendo utilizados en un alto porcentaje de pacientes, ya que los prometedores resultados obtenidos por esos fármacos alternativos y determinadas combinaciones en estudios in vitro y modelos animales no se han traducido en una evidente superioridad en los estudios clínicos con la frecuencia que se hubiera esperado. Dicho esto, existen datos que sugieren que determinadas alternativas pueden ofrecer ventajas en situaciones concretas. En general, es necesario un manejo individualizado y experto de los pacientes para decidir la mejor terapia en base al foco, la gravedad y las complicaciones, las características de los pacientes y los datos microbiológicos

Performance of penicillinase detection tests in Staphylococcus epidermidis: comparison of different phenotypic methods.

BACKGROUND: Staphylococcus epidermidis is the leading coagulase negative staphylococci (CoNS) species associated with healthcare associated infections. In order to de-escalate antimicrobial therapy, isolates of S. epidermidis lacking the blaZ gene should be eligible for targeted antimicrobial therapy. However, testing the susceptibility of coagulase negative staphylococci (CoNS) to penicillin G is no longer recommended by EUCAST, given the low performances for penicillinase detection in CoNS. The objective of this work was to determine a phenotypic method with high performance for detecting penicillinase production in S. epidermidis. RESULTS: Four techniques for the detection of penicillinase production (disk diffusion, zone edge test, nitrocefin test, Minimal Inhibitory Concentration (MIC) by automated system Vitek2®) were evaluated on 182 S. epidermidis isolates, using identification of blaZ gene by PCR as the reference method. The performance of the methods for penicillinase detection was compared by the sensitivity, the specificity, the negative predictive value and the positive predictive value, and with Cohen's kappa statistical test. Among the 182 S. epidermidis included in this study, 55 carried the blaZ gene. The nitrocefin test, characterized by a poor sensitivity (91%), was therefore excluded from S. epidermidis penicillinase detection. The algorithm proposed here for the penicillinase detection in S. epidermidis involved two common antimicrobial susceptibility techniques: disk diffusion method and MIC by Vitek2® system. Disk diffusion method, interpreted with a 26 mm breakpoint for penicillin G, was associated with a high sensitivity (98%) and specificity (100%). This method was completed with zone edge test for S. epidermidis with penicillin G diameter from 26 to 35 mm (sensitivity of 98%). The Vitek2® system is associated with a low sensitivity (93%) and a high specificity (99%) This low sensitivity is associated with false negative results, in isolates with 0.12 mg/L Penicillin G MIC values and blaZ positive. Thus for penicillin G MIC of 0.06 mg/L or 0.12 mg/L, a second step with disc diffusion method is suggested. CONCLUSIONS: According to our results, the strategy proposed here allows the interpretation of penicillin G susceptibility in S. epidermidis isolates, with an efficient detection of penicillin G resistance.

Australian Gonococcal Surveillance Programme Annual Report, 2019.

The Australian Gonococcal Surveillance Programme (AGSP) has continuously monitored antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae since 1981. In 2019, a total of 9,668 clinical isolates of gonococci from the public and private sector in all jurisdictions were tested for in vitro antimicrobial susceptibility by standardised methods. The current treatment recommendation for gonorrhoea, for the majority of Australia, continues to be dual therapy with ceftriaxone and azithromycin. Decreased susceptibility (DS) to ceftriaxone (minimum inhibitory concentration [MIC] value ≥ 0.06 mg/L) was found nationally in 1.3% of isolates. Five N. gonorrhoeae clinical isolates were ceftriaxone-resistant (MIC value ≥ 0.25 mg/L), and therefore also resistant to penicillin; all were resistant to ciprofloxacin but susceptible to azithromycin. These isolates were reported from Victoria (3), non-remote Western Australia (1) and New South Wales (1). Resistance to azithromycin (MIC value ≥ 1.0 mg/L) was found nationally in 4.6% of N. gonorrhoeae isolates, continuing a downward trend observed and reported since 2017. Isolates with high-level resistance to azithromycin (MIC value ≥ 256 mg/L) continue to be reported sporadically in Australia, with eight detected in 2019: two each from New South Wales, Queensland, and Victoria, and one each from Tasmania and non-remote Western Australia. In 2019, in Australia, 2,136 gonococcal isolates (22.1%) were penicillin resistant; however, there remains considerable variation by jurisdiction, and in some remote settings there is little resistance and this drug is recommended empiric therapy. In 2019, in the remote Northern Territory, no penicillin resistance was reported, however in remote Western Australia six out of 85 isolates (7.1%) were penicillin resistant. There was no ciprofloxacin resistance reported from isolates tested from remote regions of the Northern Territory, and ciprofloxacin resistance rates remain comparatively low (7/85; 8.2%) in remote Western Australia.

Surveillance of penicillin resistance of Neisseria meningitidis strains from invasive infections between 2013 and 2018 in Turkey.

Neisseria meningitidis (N. meningitidis) is regarded as the leading cause of bacterial meningitis in many regions of the world. The empiric antimicrobial treatment is mainly based on antimicrobial resistance and patient characteristics. We aimed to analyze susceptibility patterns of N. meningitidis strains isolated in Turkey. Invasive meningococci collected in a multicenter, hospital-based, epidemiological surveillance study of pediatric (0-18 years of age) bacterial meningitis cases between 2013 and 2018 were studied. Five isolates (8.7%) displayed resistance to penicillin-G, while 13 isolates (22.8%) had intermediate susceptibility. All isolates were cefotaxime and rifampin susceptible. The data shows appropriateness of third-generation cephalosporins in empirical use for meningococcal infections in children. Since Turkey is located in a transition zone geographically, surveillance reports are very crucial.

Molecular Analysis of PBP1A in Streptococcus pneumoniae Isolated from Clinical and Normal Flora Samples in Tehran, Iran: A Multicenter Study.

The emergence of high-level penicillin resistance in pneumococcal isolates has seriously complicated the treatment of pneumococcal infections in recent years. The purpose of this study was to determine the serotype, antimicrobial susceptibility, molecular typing, and genetic analysis of the penicillin-binding protein 1a (pbp1a) gene in pneumococcal isolates with high-level resistance to penicillin in Tehran, Iran. PCR amplification, sequencing, and data analysis of the pbp1a gene were carried out for isolates with high-level resistance to penicillin. Antibiotic susceptibility tests showed that the multiple drug resistance pattern "E-CD-OX-TS-T" was the most prevalent (18.0%). The most common serotypes were serotypes 14 (21%), 19F (17%), 23F (16%), and 3 (16%). The highest mutation rates were found in STMK conserved motifs, but no mutation was detected in the other two sequence motifs (SRN and KTG). High-level resistant isolates showed mutations at residues TSQF (574-577) NTGY. Pneumococcal isolates have experienced shifts toward higher penicillin minimal inhibitory concentration levels and other ß-lactams. The results of this study show that the presence of multiple substitutions in the pbp1a gene in pneumococcal isolates is highly associated with a reduced affinity to penicillin.

Insights into the antibacterial mechanism of PEGylated nano-bacitracin A against Streptococcus pneumonia: both penicillin-sensitive and penicillin-resistant strains.

BACKGROUND: Multidrug-resistant (MDR) Streptococcus pneumonia constitute a major worldwide public health concern. MATERIALS AND METHODS: In our preliminary study, PEGylated nano-self-assemblies of bacitracin A (PEGylated Nano-BA12K) showed strong antibacterial potency against reference S. pneumonia strain (ATCC 49619). In this study, the possibility of applying PEGylated Nano-BA12K against penicillin-resistant S. pneumonia was further investigated. In addition, the underlying antibacterial mechanism of PEGylated Nano-BA12K against both sensitive and resistant S. pneumonia was also clarified systematically, since S. pneumonia was naturally resistant to its unassembled counterpart bacitracin A (BA). RESULTS: PEGylated Nano-BA12K showed strong antibacterial potency against 13 clinical isolates of S. pneumonia, including five penicillin-resistant strains. Structural changes, partial collapse, and even lysis of both penicillin-sensitive and penicillin-resistant bacteria were observed after incubation with PEGylated Nano-BA12K via transmission electron microscopy and atomic force microscopy. Thus, the cell wall or/and cell membrane might be the main target of PEGylated Nano-BA12K against S. pneumonia. PEGylated Nano-BA12K exhibited limited effect on the permeabilization and peptidoglycan content of cell wall. Surface pressure measurement suggested that PEGylated Nano-BA12K was much more tensioactive than BA, which was usually translated into a good membranolytic effect, and is helpful to permeabilize the cell membrane and damage membrane integrity, as evidenced by depolarization of the membrane potential, permeabilization of membrane and leakage of calcein from liposomes. CONCLUSION: Collectively, great cell membrane permeability and formidable membrane disruption may work together for the strong antibacterial activity of PEGylated Nano-BA12K against S. pneumonia. Taken together, PEGylated Nano-BA12K has excellent potential against both penicillin-sensitive and penicillin-resistant S. pneumonia and might be suitable for the treatment of S. pneumonia infectious diseases.

New Mutations of Penicillin-Binding Proteins in Streptococcus agalactiae Isolates from Cattle with Decreased Susceptibility to Penicillin.

Streptococcus agalactiae is a causal agent of bovine mastitis and is treated by ß-lactam antibiotics (BLAs). Compared to penicillin-resistant S. agalactiae from humans, resistant strains in bovine are rarely reported. In this study, we aimed to investigate BLA resistance and mutations in penicillin-binding proteins (PBPs) of S. agalactiae in central and northeast China. The minimum inhibitory concentrations (MICs) of 129 penicillin-resistant S. agalactiae isolates from cows with mastitis were determined, and the related PBP genes were detected and sequenced. All strains were unsusceptible to penicillin G and mostly resistant to ampicillin, cefalexin, and ceftiofur sodium. One hundred twenty-nine strains were divided into 4 clonal groups and 8 sequence types by multilocus sequence typing analysis. We found a set of new substitutions in PBP1B, PBP2B, and PBP2X from most strains isolated from three provinces. The strains with high PBP mutations showed a broader unsusceptible spectrum and higher MICs than those with few or single mutation. Our research indicates unpredicted mutations in the PBP genes of S. agalactiae isolated from cows with mastitis treated by BLAs. This screening is the first of S. agalactiae from cattle.

Antimicrobial resistance of Neisseria gonorrhoeae in Germany: low levels of cephalosporin resistance, but high azithromycin resistance.

BACKGROUND: The widespread antimicrobial resistance of Neisseria gonorrhoeae is a serious problem for the treatment and control of gonorrhoea. Many of the previously effective therapeutic agents are no longer viable. Because N. gonorrhoeae infections are not reportable in Germany, only limited data on disease epidemiology and antimicrobial susceptibility patterns are available. The Gonococcal Resistance Network (GORENET) is a surveillance project to monitor trends in the antimicrobial susceptibility of N. gonorrhoeae in Germany in order to guide treatment algorithms and target future prevention strategies. METHODS: Between April 2014 and December 2015, data on patient-related information were collected from laboratories nationwide, and susceptibility testing was performed on 537 N. gonorrhoeae isolates forwarded from the network laboratories to the Conciliar Laboratory for gonococci. Susceptibility results for cefixime, ceftriaxone, azithromycin, ciprofloxacin and penicillin were defined according to EUCAST 4.0 standards. Percentages, medians and interquartile ranges (IQR) were calculated. RESULTS: Altogether, 90% of isolates were from men. The median age was 32 (IQR 25-44) years for men and 25 (IQR 22-40) years for women (p-value < 0.001). The most frequently tested materials among men were urethral (96.1%) and rectal swabs (1.7%), and among women, it was mainly endocervical and vaginal swabs (84.3%). None of the isolates were resistant to ceftriaxone. Furthermore, 1.9% (in 2014) and 1.4% (in 2015) of the isolates were resistant to cefixime, 11.9% and 9.8% showed resistance against azithromycin, 72.0% and 58.3% were resistant to ciprofloxacin, and 29.1% and 18.8% were resistant to penicillin. CONCLUSIONS: Resistance to ceftriaxone was not detected, and the percentage of isolates with resistance to cefixime was low, whereas azithromycin resistance showed high levels during the observation period. The rates of ciprofloxacin resistance and penicillin resistance were very high across Germany. Continued surveillance of antimicrobial drug susceptibilities for N. gonorrhoeae remains highly important to ensure efficient disease management.

CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro.

Sepsis is a life-threatening health condition caused by infectious pathogens of the respiratory tract, and accounts for 28-50% of annual deaths in the US alone. Current treatment regimen advocates the use of corticosteroids as adjunct treatment with antibiotics, for their broad inhibitory effect on the activity and production of pro-inflammatory mediators. However, despite their use, corticosteroids have not proven to be able to reverse the death incidence among septic patients. We have previously demonstrated the potential for neuroendocrine factors to directly influence Streptococcus pneumoniae virulence, which may in turn mediate disease outcome leading to sepsis and septic shock. The current study investigated the role of Corticotropin-releasing hormone (CRH) in mediating key markers of pneumococcal virulence as important phenotypic determinants of sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal strain with CRH promoted growth rate, increased capsule thickness and penicillin resistance, as well as induced pneumolysin gene expression. These results thus provide significant insights of CRH-pathogen interactions useful in understanding the underlying mechanisms of neuroendocrine factor's role in the onset of community acquired pneumonias (CAP), sepsis and septic shock.

In Vivo Pharmacodynamic Target Assessment of Delafloxacin against Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae in a Murine Lung Infection Model.

Delafloxacin is a broad-spectrum anionic fluoroquinolone under development for the treatment of bacterial pneumonia. The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae Four isolates of each species were utilized for in vivo studies: for S. aureus, one methicillin-susceptible and three methicillin-resistant isolates; S. pneumoniae, two penicillin-susceptible and two penicillin-resistant isolates; K. pneumoniae, one wild-type and three extended-spectrum beta-lactamase-producing isolates. MICs were determined using CLSI methods. A neutropenic murine lung infection model was utilized for all treatment studies, and drug dosing was by the subcutaneous route. Single-dose plasma pharmacokinetics was determined in the mouse model after administration of 2.5, 10, 40, and 160 mg/kg. For in vivo studies, 4-fold-increasing doses of delafloxacin (range, 0.03 to 160 mg/kg) were administered every 6 h (q6h) to infected mice. Treatment outcome was measured by determining organism burden in the lung (CFU counts) at the end of each experiment (24 h). The Hill equation for maximum effect (Emax) was used to model the dose-response data. The magnitude of the PK/PD index, the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC), associated with net stasis and 1-log kill endpoints was determined in the lung model for all isolates. MICs ranged from 0.004 to 1 mg/liter. Single-dose PK parameter ranges include the following: for maximum concentration of drug in serum (Cmax), 2 to 70.7 mg/liter; AUC from 0 h to infinity (AUC0-∞), 2.8 to 152 mg · h/liter; half-life (t1/2), 0.7 to 1 h. At the start of therapy mice had 6.3 ± 0.09 log10 CFU/lung. In control mice the organism burden increased 2.1 ± 0.44 log10 CFU/lung over the study period. There was a relatively steep dose-response relationship observed with escalating doses of delafloxacin. Maximal organism reductions ranged from 2 log10 to more than 4 log10 The median free-drug AUC/MIC magnitude associated with net stasis for each species group was 1.45, 0.56, and 40.3 for S. aureus, S. pneumoniae, and K. pneumoniae, respectively. AUC/MIC targets for the 1-log kill endpoint were 2- to 5-fold higher. Delafloxacin demonstrated in vitro and in vivo potency against a diverse group of pathogens, including those with phenotypic drug resistance to other classes. These results have potential relevance for clinical dose selection and evaluation of susceptibility breakpoints for delafloxacin for the treatment of lower respiratory tract infections involving these pathogens.

Old Drugs To Treat Resistant Bugs: Methicillin-Resistant Staphylococcus aureus Isolates with mecC Are Susceptible to a Combination of Penicillin and Clavulanic Acid.

ß-Lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) is mediated by the expression of an alternative penicillin-binding protein 2a (PBP2a) (encoded by mecA) with a low affinity for ß-lactam antibiotics. Recently, a novel variant of mecA, known as mecC, was identified in MRSA isolates from both humans and animals. In this study, we demonstrate that mecC-encoded PBP2c does not mediate resistance to penicillin. Rather, broad-spectrum ß-lactam resistance in MRSA strains carrying mecC (mecC-MRSA strains) is mediated by a combination of both PBP2c and the distinct ß-lactamase encoded by the blaZ gene of strain LGA251 (blaZLGA251), which is part of mecC-encoding staphylococcal cassette chromosome mec (SCCmec) type XI. We further demonstrate that mecC-MRSA strains are susceptible to the combination of penicillin and the ß-lactam inhibitor clavulanic acid in vitro and that the same combination is effective in vivo for the treatment of experimental mecC-MRSA infection in wax moth larvae. Thus, we demonstrate how the distinct biological differences between mecA- and mecC-encoded PBP2a and PBP2c have the potential to be exploited as a novel approach for the treatment of mecC-MRSA infections.

Synthesis and biological evaluation of levofloxacin core-based derivatives with potent antibacterial activity against resistant Gram-positive pathogens.

A series of C10 non-basic building block-substituted, levofloxacin core-based derivatives were synthesized in 43-86% yield. The antibacterial activity of these new fluoroquinolones was evaluated using a standard broth microdilution technique. The quinolone (S)-9-fluoro-10-(4-hydroxypiperidin-1-yl)-3-methyl-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid L-arginine tetrahydrate exhibited superior antibacterial activity against quinolone-susceptible and resistant strains compared with the clinically used fluoroquinolones ciprofloxacin, levofloxacin, moxifloxacin, penicillin, and vancomycin, especially to the methicillin-resistant Staphylococcus aureus clinical isolates, penicillin-resistant Streptococcus pneumoniae clinical isolates, and Streptococcus pyogenes.

Characterization of pre-antibiotic era Klebsiella pneumoniae isolates with respect to antibiotic/disinfectant susceptibility and virulence in Galleria mellonella.

The EGD Murray collection consists of approximately 500 clinical bacterial isolates, mainly Enterobacteriaceae, isolated from around the world between 1917 and 1949. A number of these "Murray" isolates have subsequently been identified as Klebsiella pneumoniae. Antimicrobial susceptibility testing of these isolates showed that over 30% were resistant to penicillins due to the presence of diverse blaSHV ß-lactamase genes. Analysis of susceptibility to skin antiseptics and triclosan showed that while the Murray isolates displayed a range of MIC/minimal bactericidal concentration (MBC) values, the mean MIC value was lower than that for more modern K. pneumoniae isolates tested. All Murray isolates contained the cation efflux gene cepA, which is involved in disinfectant resistance, but those that were more susceptible to chlorhexidine were found to have a 9- or 18-bp insertion in this gene. Susceptibility to other disinfectants, e.g., H2O2, in the Murray isolates was comparable to that in modern K. pneumoniae isolates. The Murray isolates were also less virulent in Galleria and had a different complement of putative virulence factors than the modern isolates, with the exception of an isolate related to the modern lineage CC23. More of the modern isolates (41% compared to 8%) are classified as good/very good biofilm formers, but there was overlap in the two populations. This study demonstrated that a significant proportion of the Murray Klebsiella isolates were resistant to penicillins before their routine use. This collection of pre-antibiotic era isolates may provide significant insights into adaptation in K. pneumoniae in relation to biocide susceptibility.

Serotype and genotype distribution among invasive Streptococcus pneumoniae isolates in Colombia, 2005-2010.

In Colombia, a laboratory-based surveillance of invasive Streptococcus pneumoniae isolates as part of SIREVA II PAHO has been conducted since 1994. This study describes the serotype distribution, antimicrobial resistance, and genetic relationships of pneumococcal isolates recovered in Colombia from 2005 to 2010. In this study, demographic data of invasive S. pneumoniae isolates were analyzed, and antimicrobial susceptibility patterns were determined. Pulse field gel electrophoresis (n = 629) and multilocus sequence typing (n = 10) were used to determine genetic relationship of isolates with minimal inhibitory concentration to penicillin ≥0.125 µg/mL. A total of 1775 isolates of S. pneumoniae were obtained. Fifteen serotypes accounted for 80.7% of isolates. Serotype 14 (23.1%) was the most frequent in the general population. Penicillin resistance was 30.7% in meningitis and 9.0% in non-meningitis. Clones Spain(6B)ST90, Spain(9V)ST156, Spain(23F)ST81, and Colombia(23F)ST338 were associated to isolates. Additionally, serotype 6A isolates were associated with ST460 and ST473, and 19A isolates with ST276, ST320, and ST1118. In conclusion, the surveillance program provided updated information of trends in serotype distribution, antimicrobial resistance and the circulation of clones in invasive pneumococcal diseases. These results could be helpful to understand the epidemiology of S. pneumoniae in Colombia, and provide a baseline to measure the impact of vaccine introduction.

Macrolide resistant Streptococcus pneumoniae in Charoenkrung Pracharak Hospital, Thailand.

Macrolide resistant Streptococcus pneumoniae has been increasing rapidly in Southeast Asia. A review from 2000 through 2011 at Charoenkrung Pracharak Hospital that evaluated drug resistance to erythromycin found S. pneumoniae from 158 of the 390 (40.5%) patients: 3.6% intermediate, 36.9% highly resistant. A significant correlation was found between macrolide resistant S. pneumoniae and penicillin resistance (p<0.001), macrolide susceptible pneumococci and penicillin susceptibility (p<0.001). Trends of macrolide resistant S. pneumoniae at Charoenkrung Pracharak Hospital were found to have increased. Therefore, macrolide monotherapy should be avoided or care should be taken for prophylaxis or treatment in the patient suspected of S. pneumoniae infection.

The protease inhibitor JO146 demonstrates a critical role for CtHtrA for Chlamydia trachomatis reversion from penicillin persistence.

The Chlamydia trachomatis serine protease HtrA (CtHtrA) has recently been demonstrated to be essential during the replicative phase of the chlamydial developmental cycle. A chemical inhibition strategy (serine protease inhibitor JO146) was used to demonstrate this essential role and it was found that the chlamydial inclusions diminish in size and are lost from the cell after CtHtrA inhibition without formation of viable elementary bodies. The inhibitor (JO146) was used in this study to investigate the role of CtHtrA for penicillin persistence and heat stress conditions for Chlamydia trachomatis. JO146 addition during penicillin persistence resulted in only minor reductions (~1 log) in the final viable infectious yield after persistent Chlamydia were reverted from persistence. However, JO146 treatment during the reversion and recovery from penicillin persistence was completely lethal for Chlamydia trachomatis. JO146 was completely lethal when added either during heat stress conditions, or during the recovery from heat stress conditions. These data together indicate that CtHtrA has essential roles during some stress environments (heat shock), recovery from stress environments (heat shock and penicillin persistence), as well as the previously characterized essential role during the replicative phase of the chlamydial developmental cycle. Thus, CtHtrA is an essential protease with both replicative phase and stress condition functions for Chlamydia trachomatis.

Efeito da penicilina G a cada três semanas sobre o surgimento de Streptococcus viridans resistentes à penicilina na microflora oral / Effect of penicillin G every three weeks on oral microflora by penicillin resistant Viridans Streptococci

FUNDAMENTO: Penicilina G benzatina a cada 3 semanas é o protocolo padrão para a profilaxia secundária para febre reumática recorrente. OBJETIVO: Avaliar o efeito da penicilina G benzatina em Streptococcus sanguinis e Streptococcus oralis em pacientes com doença valvular cardíaca, devido à febre reumática com recebimento de profilaxia secundária. MÉTODOS: Estreptococos orais foram avaliados antes (momento basal) e após 7 dias (7º dia) iniciando-se com penicilina G benzatina em 100 pacientes que receberam profilaxia secundária da febre reumática. Amostras de saliva foram avaliadas para verificar a contagem de colônias e presença de S. sanguinis e S. oralis. Amostras de saliva estimulada pela mastigação foram serialmente diluídas e semeadas em placas sobre agar-sangue de ovelhas seletivo e não seletivo a 5% contendo penicilina G. A identificação da espécie foi realizada com testes bioquímicos convencionais. Concentrações inibitórias mínimas foram determinadas com o Etest. RESULTADOS: Não foram encontradas diferenças estatísticas da presença de S. sanguinis comparando-se o momento basal e o 7º dia (p = 0,62). No entanto, o número existente de culturas positivas de S. oralis no 7º dia após a Penicilina G benzatina apresentou um aumento significativo em relação ao valor basal (p = 0,04). Não houve diferença estatística existente entre o momento basal e o 7º dia sobre o número de S. sanguinis ou S. oralis UFC/mL e concentrações inibitórias medianas. CONCLUSÃO: O presente estudo mostrou que a Penicilina G benzatina a cada 3 semanas não alterou a colonização por S. sanguinis, mas aumentou a colonização de S. oralis no 7º dia de administração. Portanto, a susceptibilidade do Streptococcus sanguinis e Streptococcus oralis à penicilina G não foi modificada durante a rotina de profilaxia secundária da febre reumática utilizando a penicilina G. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

BACKGROUND: Benzathine penicillin G every 3 weeks is the standard protocol for secondary prophylaxis for recurrent rheumatic fever. OBJECTIVE: Assess the effect of Benzathine penicillin G on Streptococcus sanguinis and Streptococcus oralis in patients with cardiac valvular disease due to rheumatic fever receiving secondary prophylaxis. METHODS: Oral streptococci were evaluated before (baseline) and after 7 days (day 7) with Benzathine penicillin G in 100 patients receiving routine secondary rheumatic fever prophylaxis. Saliva samples were evaluated for colony count and presence of S. sanguinis and S. oralis. Chewing-stimulated saliva samples were serially diluted and plated onto both nonselective and selective 5% sheep blood agar containing penicillin G. The species were identified using conventional biochemical tests. Minimal inhibitory concentrations were determined with the Etest. RESULTS: No statistical differences were found in the presence of S. sanguinis comparing baseline and day 7 (p = 0.62). However, the existing number of positive cultures of S. oralis on day 7 after Benzathine penicillin G presented a significant increase compared to baseline (p = 0.04). No statistical difference was found between baseline and day 7 concerning the number of S. sanguinis or S. oralis CFU/mL and median minimal inhibitory concentrations. CONCLUSION: This study showed that Benzathine penicillin G every 3 weeks did not change the colonization by S. sanguinis, but increased colonization of S. oralis on day 7 of administration. Therefore, susceptibility of Streptococcus sanguinis and Streptococcus oralis to penicillin G was not modified during the penicillin G routine secondary rheumatic fever prophylaxis. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

Effect of penicillin G every three weeks on oral microflora by penicillin resistant Viridans Streptococci.

BACKGROUND: Benzathine penicillin G every 3 weeks is the standard protocol for secondary prophylaxis for recurrent rheumatic fever. OBJECTIVE: Assess the effect of Benzathine penicillin G on Streptococcus sanguinis and Streptococcus oralis in patients with cardiac valvular disease due to rheumatic fever receiving secondary prophylaxis. METHODS: Oral streptococci were evaluated before (baseline) and after 7 days (day 7) with Benzathine penicillin G in 100 patients receiving routine secondary rheumatic fever prophylaxis. Saliva samples were evaluated for colony count and presence of S. sanguinis and S. oralis. Chewing-stimulated saliva samples were serially diluted and plated onto both nonselective and selective 5% sheep blood agar containing penicillin G. The species were identified using conventional biochemical tests. Minimal inhibitory concentrations were determined with the Etest. RESULTS: No statistical differences were found in the presence of S. sanguinis comparing baseline and day 7 (p = 0.62). However, the existing number of positive cultures of S. oralis on day 7 after Benzathine penicillin G presented a significant increase compared to baseline (p = 0.04). No statistical difference was found between baseline and day 7 concerning the number of S. sanguinis or S. oralis CFU/mL and median minimal inhibitory concentrations. CONCLUSION: This study showed that Benzathine penicillin G every 3 weeks did not change the colonization by S. sanguinis, but increased colonization of S. oralis on day 7 of administration. Therefore, susceptibility of Streptococcus sanguinis and Streptococcus oralis to penicillin G was not modified during the penicillin G routine secondary rheumatic fever prophylaxis.