Dental healthcare costs of children living in Amsterdam and associated socio-demographic characteristics.

OBJECTIVES: The aim of this study was to assess associations between socio-demographic characteristics and dental costs of children living in Amsterdam. Having incurred dental costs was an indicator for having visited the dentist. Having incurred low or high dental costs may indicate the type of dental care provided (periodic examination, preventive care or restorative treatment). METHODS: This study followed a cross-sectional, observational design. The research population contained all children up until 17 years living in Amsterdam in 2016. Dental costs from all Dutch healthcare insurance companies were obtained via Vektis, and socio-demographic data were obtained from Statistics Netherlands (CBS). The study population was stratified into age groups: 0-4 and 5-17 years. Dental costs were classified as no dental costs (0 euros), low dental costs (>0 to <100 euros) or high dental costs (≥100 euros). Univariable and multivariable logistic regression analyses were performed to study the distribution of dental costs and associations with socio-demographic child and parent variables. RESULTS: In the population of 142 289 children, 44 887 (31.5%) incurred no dental costs, 32 463 (22.8%) incurred low dental costs and 64 939 (45.6%) incurred high dental costs. Among children of 0-4 years, a much larger proportion (70.2%) incurred no dental costs, compared to those of 5-17 years (15.8%). In both age groups, migration background (adjusted Odds Ratio (aOR) range 1.23-1.98), low(er) household income (aOR range 0.45-0.93), low(er) parental educational level (aOR range 0.51-0.87) and living in a single-parent household (aOR range 0.89-0.91) were strongly associated with incurring high (vs. low) dental costs. Furthermore, in 5-17-year-old children, a lower level of secondary or vocational education (aOR range 1.12-1.17) and living in households receiving social benefits (aOR 1.23) were associated with incurring high dental costs. CONCLUSIONS: Among children living in Amsterdam in 2016, one in three children did not visit a dentist. For children that did visit a dentist, those with a migration background, low parental educational level and from a low household income were more likely to incur high dental costs, which could be indicative for additional restorative treatment. Hence, patterns of oral healthcare consumption, specified by type of dental care over time, and their association with oral health status, are targets for future research.

Detection of Streptococcus pyogenes virulence genes in Streptococcus dysgalactiae subsp. equisimilis from Vellore, India.

Streptococcus dysgalactiae subsp. equisimilis (SDSE), belonging to the group C and G streptococci, are human pathogens reported to cause clinical manifestations similar to infections caused by Streptococcus pyogenes. To scrutinize the distribution of gene coding for S. pyogenes virulence factors in SDSE, 255 isolates were collected from humans infected with SDSE in Vellore, a region in southern India, with high incidence of SDSE infections. Initial evaluation indicated SDSE isolates comprising of 82.35% group G and 17.64% group C. A multiplex PCR system was used to detect 21 gene encoding virulence-associated factors of S. pyogenes, like superantigens, DNases, proteinases, and other immune modulatory toxins. As validated by DNA sequencing of the PCR products, sequences homologous to speC, speG, speH, speI, speL, ssa and smeZ of the family of superantigen coding genes and for DNases like sdaD and sdc were detected in the SDSE collection. Furthermore, there was high abundance (48.12% in group G and 86.6% in group C SDSE) of scpA, the gene coding for C5a peptidase in these isolates. Higher abundance of S. pyogenes virulence factor genes was observed in SDSE of Lancefield group C as compared to group G, even though the incidence rates in former were lower. This study not only substantiates detection of S. pyogenes virulence factor genes in whole genome sequenced SDSE but also makes significant contribution towards the understanding of SDSE and its increasing virulence potential.

The importance of Rydberg orbitals in dissociative ionization of small hydrocarbon molecules in intense laser fields.

Much of our intuition about strong-field processes is built upon studies of diatomic molecules, which typically have electronic states that are relatively well separated in energy. In polyatomic molecules, however, the electronic states are closer together, leading to more complex interactions. A combined experimental and theoretical investigation of strong-field ionization followed by hydrogen elimination in the hydrocarbon series C2D2, C2D4 and C2D6 reveals that the photofragment angular distributions can only be understood when the field-dressed orbitals rather than the field-free orbitals are considered. Our measured angular distributions and intensity dependence show that these field-dressed orbitals can have strong Rydberg character for certain orientations of the molecule relative to the laser polarization and that they may contribute significantly to the hydrogen elimination dissociative ionization yield. These findings suggest that Rydberg contributions to field-dressed orbitals should be routinely considered when studying polyatomic molecules in intense laser fields.

Draft Genome Sequence of Streptococcus dysgalactiae subsp. equisimilis Strain C161L1 Isolated in Vellore, India.

Streptococcus dysgalactiae subsp. equisimilis belongs to the ß-hemolytic group C and G pyogenic group of streptococci. Here, we report the draft genome of the S. dysgalactiae subsp. equisimilis strain C161L1 from Vellore, a region in southern India with a high incidence rate of S. dysgalactiae subsp. equisimilis infection. This genome is 2.1 Mb long, with a 39.82% G+C content, and encodes 2,022 genes.

Members of a new subgroup of Streptococcus anginosus harbor virulence related genes previously observed in Streptococcus pyogenes.

Conventionally categorized as commensals, the Streptococci of the species S. anginosus are facultative human pathogens that are difficult to diagnose and often overlooked. Furthermore, detailed investigation and diagnosis of S. anginosus infections is hampered by unexplored taxonomy and widely elusive molecular pathogenesis. To explore their pathogenic potential, S. anginosus isolates collected from patients of two geographical locations (Vellore, India and Leipzig, Germany) were subjected to multi-locus sequence analysis (MLSA). This analysis revealed the potential presence of a new distinct clade of the species S. anginosus, tentatively termed here as genomosubspecies vellorensis. A complementary PCR-based screening for S. pyogenes virulence factor as well as antibiotic resistance genes revealed not only the presence of superantigen- and extracellular DNase coding genes identical to corresponding genes of S. pyogenes, but also of erythromycin and tetracycline resistance genes in the genomes of the analyzed S. anginosus isolates, thus posing a matter of significant health concern. Identification of new pathogenic S. anginosus strains capable of causing difficult to treat infections may pose additional challenges to the diagnosis and treatment of Streptococcus based infections.

Preventable and potentially preventable deaths in severely injured patients: a retrospective analysis including patterns of errors.

PURPOSE: Analyzing preventable and potentially preventable deaths is a well-known procedure for improving trauma care. This study analyzes preventable and potentially preventable deaths in German trauma patients. METHODS: Patients aged between 16 and 75 years with an Injury Severity Score >15 who were primary admitted from July 2002 to December 2011 were analyzed in this study. Data from the patients' hospital records were retrospectively analyzed, and cases were categorized as preventable, potentially preventable, and non-preventable deaths. In addition, trauma management was screened for errors. RESULTS: 2304 patients were admitted from July 2002 to December 2011. 763 of which fulfilled the defined criteria. The mortality rate was 25.3 %. Eight cases (4.2 %) were declared as preventable deaths and 31 cases (16.1 %) as potentially preventable deaths. The most common errors in preclinical trauma care related to airway management. The main clinical error was insufficient hemorrhage control. Fluid overload from infusion was the second most common fault in both. CONCLUSIONS: Preventable and potentially preventable errors still occur in the treatment of severely injured patients. Errors in hemorrhage control and airway management are the most common human treatment errors. The knowledge of these errors could help to improve trauma care in the future.

Non-invasive Prenatal Testing (NIPT): Better Meet an Expert!: The Case of a Late Detected Trisomy 13 Reveals Structural Problems in NIPT Counselling and Highlights Substantial Risks for the Reproductive Autonomy.

While NIPT is being implemented rapidly, the implementation of a corresponding specialized counselling process in many respects lags behind. As a consequence, legal requirements and other testing conditions sometimes are not fulfilled adequately. The reported case illustrates the importance of trained personnel in the counselling and NIPT process and shows so far neglected risks for the pregnant woman and her reproductive autonomy.

Relationship between general movements in neonates who were growth restricted in utero and prenatal Doppler flow patterns.

OBJECTIVE: To investigate whether Doppler pulsatility indices (PIs) of the fetal circulation in cases of fetal growth restriction (FGR) are associated with the general movements (GMs) of the neonate after birth. METHODS: This was a prospective observational cohort study including pregnancies with FGR diagnosed between June 2012 and September 2014. A diagnosis of FGR was based on an abdominal circumference or estimated fetal weight < 10th percentile (in conjuction with abnormal Doppler) or declining fetal growth of at least 30 percentiles with respect to previous size measurements. Doppler parameters of the umbilical artery (UA), fetal middle cerebral artery (MCA) and ductus venosus (DV) were measured maximally 1 week prior to delivery. Cerebroplacental ratio (CPR) was calculated as MCA-PI divided by UA-PI. We assessed the quality of neonatal GMs 7 days after birth, around the due date if cases were born preterm, and at 3 months post-term. We performed a detailed analysis of the motor repertoire by calculating a motor optimality score (MOS). RESULTS: Forty-eight FGR cases were included with a median gestational age at delivery of 35 (range, 26-40) weeks. UA-PI, MCA-PI and CPR correlated strongly (ρ, -0.374 to 0.472; P < 0.01) with the MOS on day 7 after birth, but DV-PI did not. Doppler PI measurements did not correlate with MOS at 3 months post-term. CONCLUSION: Fetal arterial Doppler measurements are associated with the quality of neonatal GMs 1 week after birth, but this association is no longer evident at 3 months post-term. Brain sparing in particular is associated strongly with GMs of an abnormal quality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Correlation between Doppler flow patterns in growth-restricted fetuses and neonatal circulation.

OBJECTIVES: To investigate whether prenatal Doppler parameters in growth-restricted fetuses are correlated with neonatal circulatory changes. METHODS: In 43 cases of suspected fetal growth restriction (FGR), serial Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) pulsatility index (PI) were performed. The last measurement, closest to delivery (< 1 week before birth), was used for analysis. Neonatal circulation was assessed for 2 h/day on Days 1-5, 8 and 15 by near-infrared spectroscopy (NIRS) of the cerebral, renal and splanchnic regions. We calculated fractional tissue oxygen extraction (FTOE) as: (arterial oxygen saturation - NIRS value)/arterial oxygen saturation. The following ratios were calculated: cerebroplacental ratio (CPR; MCA-PI/UA-PI), cerebrorenal ratio (CRR; cerebral/renal FTOE) and cerebrosplanchnic ratio (CSR; cerebral/splanchnic FTOE). Spearman's rank correlation coefficient (ρ) was calculated between prenatal Doppler parameters and neonatal NIRS variables. These analyses were carried out for the entire group, and separately for cases of early FGR (delivered < 34 weeks) and late FGR (≥ 34 weeks). RESULTS: Fetal Doppler parameters correlated with neonatal NIRS variables on Days 1-3: UA-PI correlated with renal FTOE (Day 1: ρ = 0.454, P < 0.01) and CRR (Day 1: ρ = -0.517, P < 0.001). MCA-PI correlated with cerebral FTOE on Day 2 (ρ = 0.469, P < 0.01), approached statistical significance on Day 3 but was not correlated on Day 1. CPR correlated with CRR (Day 1: ρ = 0.474, P < 0.01). Most associations lost their statistical significance when early and late FGR subgroups were considered separately. CONCLUSION: Low MCA-PI and low CPR, indicating brain sparing before birth, are associated with low CRR after birth, indicating relatively greater blood flow to the cerebrum than to the renal region. Based on the results of this study, it could be speculated that if brain sparing is present in the fetal circulation, it persists during the first 3 days after birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Color Doppler ultrasound-guided PTBD with and without metal stent implantation by endoscopic control: prospective success and early adverse event rates.

OBJECTIVE: There are just a few reports on Color Doppler Ultrasound-guided PTBD with and without metal stent implantation by endoscopic control. Ultrasound guidance facilitates percutaneous bile duct access and avoids severe adverse events. Internal biliary drainage rate in PTBD should be as high as possible as endoscopic ultrasound-guided cholangiodrainage (EUCD) offers internal drainage regularly. We report our prospective study analyzing success, internal drainage and adverse event rates. MATERIALS AND METHODS: Between June 2009 and November 2014 overall 63 PTBDs were performed prospectively in 37 patients (18 m, 19f; age on average: 72 years) with benign (9 %) and malignant (91 %) bile duct obstruction. Ultrasound was used in combination with fluoroscopic guidance. Whenever possible, primary or early secondary metal stent implantation via PTBD by endoscopic control was performed as a one step-procedure. RESULTS: 38 of 41 (93 %) initial PTBDs (in four patients PTBD was performed twice) were successful. 22 of 63 PTBDs were follow-up examinations with different interventions. In 34 of 38 successful (89 %) PTBDs, an internal drainage (or metal stent) was implanted. 12 metal stent implantations via PTBD were performed under endoscopic control. Just 2 (5 %) permanent external drainages were inserted. In 63 performed PTBDs 5 (7.9 %) early major adverse events (no severe intrahepatic bleeding) were documented and treated without any procedure related death. When metal stent implantation was performed via PTBD no adverse event was documented. CONCLUSION: Color Doppler guided PTBD is an effective and safe method for biliary drainage avoiding severe adverse events. Primary or early secondary metal stent implantation via PTBD reduces complication risks additionally. Endoscopic control of stent implantation via PTBD is helpful for optimal stent placement.

Comparative genomics of Streptococcus pyogenes M1 isolates differing in virulence and propensity to cause systemic infection in mice.

Streptococcus pyogenes serotype M1 is a frequent cause of severe infections in humans. Some M1 isolates are pathogenic in mice and used in studies on infection pathogenesis. We observed marked differences in murine infections caused by M1 strain SF370, 5448, 5448AP or AP1 which prompted us to sequence the whole genome of isolates 5448 and AP1 for comparative analysis. Strain 5448 is known to acquire inactivating mutations in the CovRS two-component system during mouse infection, producing hypervirulent progeny such as 5448AP. Isolates AP1 and 5448AP, more than 5448, caused disseminating infections that became systemic and lethal. SF370 was not pathogenic. Phages caused gross genetic differences and increased the gene content of AP1 by 8% as compared to 5448 and SF370. Each of six examined M1 genomes contained two CRISPR-Cas systems. Phage insertion destroyed a type II CRISPR-Cas system in AP1 and other strains of serotypes M1, M3, M6 and M24, but not in M1 strains 5448, SF370, MGAS5005, A20 or M1 476. A resulting impaired defence against invading genetic elements could have led to the wealth of phages in AP1. AP1 lacks genetic features of the MGAS5005-like clonal complex including the streptodornase that drives selection for hypervirulent clones with inactivated CovRS system. Still, inactivating mutations in covS were a common genetic feature of AP1 and the MGAS5005-like isolate 5448AP. Abolished expression of the cysteine proteinase SpeB, due to CovRS inactivation could be a common cause for hypervirulence of the two isolates. Moreover, an additional protein H-coding gene and a mutation in the regulator gene rofA distinguished AP1 form other M1 isolates. In conclusion, hypervirulence of S. pyogenes M1 in mice is not limited to the MGAS5005-like genotype.

On the nature of superconductivity in the anisotropic dichalcogenide NbSe2{CoCp2}x.

We present a detailed study of the superconducting properties of the weakly pinned, quasi-two-dimensional superconductor 2H-NbSe2, and its intercalated variant NbSe2{CoCp2}0.26. The intercalation of 2H-NbSe2 with the organometallic donor molecule cobaltocene (CoCp2) hardly affects the superconducting properties within the layers. However, the properties perpendicular to the layers change significantly due to the large expansion of the layer spacings of the host lattice in the c-direction by a factor of about two. In particular, the superconducting anisotropy factor Γ increases from 3.3 in the parent compound 2H-NbSe2 up to 4.4 in the intercalated species. Therefore, NbSe2{CoCp2}0.26 is an excellent candidate to analyze how the anisotropy effects the superconducting mechanism in layered dichalcogenides, and to evaluate the various models proposed in the literature to account for the anisotropy in 2H-NbSe2. While a two-gap model and an anisotropic single-gap model are competing concepts to describe the almost linear T(2)-dependence of ΔC/T in low-dimensional dichalcogenides, our comparative study suggests that a single-gap model with an anisotropic Fermi-surface is sufficient to capture the ΔC/T(T) behavior in our samples qualitatively.

Small plasmids in Streptococcus dysgalactiae subsp. equisimilis isolated from human infections in southern India and sequence analysis of two novel plasmids.

Small plasmids are frequently found in S. pyogenes isolates from human infections in India. Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a streptococcal subspecies that is genetically similar to S. pyogenes and has a similar ecology. Therefore, we determined the distribution of small plasmids in a collection of 254 SDSE isolates, comprising 44 different emm-types and emm non-typable strains, from southern India, utilizing an established PCR based method. Briefly, 1.2% (n=3) of the isolates were positive for repA (encoding the replication initiation protein A) and 1.6% (n=4) were repB positive (encoding the replication initiation protein B). One isolate (G315) showed a co-detection of repB and dysA (encoding the bacteriocin dysgalacticin) which is characteristic for previously described pDN281/pW2580-like plasmids, observed in SDSE and S. pyogenes. The remaining plasmid bearing isolates showed no characteristic co-detection of known plasmid-associated genes. Thus, plasmids pG271 and pG279, representatives for repB and repA harboring plasmids, respectively, were analyzed. The plasmids pG271 and pG279 could be assigned to the pMV158 and the pC194/pUB110 family of rolling-circle plasmids, respectively. Like the characterized small native plasmids of S. pyogenes from India, the SDSE plasmids discovered and described in this study did not carry any of the known antibiotic resistance genes. SDSE bore less of the investigated small native plasmids that were distinct from the small native plasmids of S. pyogenes of the same geographic region. This indicates a low rate of lateral transfer of these genetic elements between these two related streptococcal species.

The dipole moment of the spin density as a local indicator for phase transitions.

The intra-atomic magnetic dipole moment - frequently called ⟨Tz⟩ term - plays an important role in the determination of spin magnetic moments by x-ray absorption spectroscopy for systems with nonspherical spin density distributions. In this work, we present the dipole moment as a sensitive monitor to changes in the electronic structure in the vicinity of a phase transiton. In particular, we studied the dipole moment at the Fe(2+) and Fe(3+) sites of magnetite as an indicator for the Verwey transition by a combination of x-ray magnetic circular dichroism and density functional theory. Our experimental results prove that there exists a local change in the electronic structure at temperatures above the Verwey transition correlated to the known spin reorientation. Furthermore, it is shown that measurement of the dipole moment is a powerful tool to observe this transition in small magnetite nanoparticles for which it is usually screened by blocking effects in classical magnetometry.

The broadband microwave spectra of the monoterpenoids thymol and carvacrol: conformational landscape and internal dynamics.

The rotational spectra of the monoterpenoids thymol and carvacrol are reported in the frequency range 2-8.5 GHz, obtained with broadband Fourier-transform microwave spectroscopy. For carvacrol four different conformations were identified in the cold conditions of the molecular jet, whereas only three conformations were observed for thymol. The rotational constants and other molecular parameters are reported and compared with quantum chemical calculations. For both molecules, line splittings due to methyl group internal rotation were observed and the resulting barrier heights could be determined. The experimental barrier heights, 4.0863(25) kJ/mol for trans-carvacrol-A, 4.4024(16) kJ/mol for trans-carvacrol-B, and 0.3699(11) kJ/mol for trans-thymol-A, are compared with similar molecules.

Differences in virulence repertoire and cell invasive potential of group A Streptococcus emm1-2 in comparison to emm1 genotype.

Group A streptococcus (GAS, Streptococcus pyogenes) type emm1 is widely associated with streptococcal invasive disease. This type is prevalent worldwide but is rare in India. Instead, emm1-2 type which is closely related to emm1 but is a distinct type is more prevalent. Although emm1 has been well characterized, information available on emm1-2 is rare. In this study we present a comparative study of both types. DNA microarray analysis showed segregation of emm1 and emm1-2 isolates into two distinct clusters. Out of 229 arrayed genes, 83-87% were present, 6-9% absent and 4-8% genes were ambiguous in emm1 isolates. emm1-2 strains harboured only 68-77%, 11-13% were absent and 10-20% ambiguous genes. Fourteen genes, present in all emm1, were completely absent in the emm1-2 isolates. sfb1 is a gene which encodes for Streptococcal fibronectin binding adhesin and invasin which has restricted distribution among different emm types of GAS. A variant of sfb1 (sfb1-2) was the only gene which was present in all emm1-2 isolates, but absent from all emm1 strains. Sfb1 and Sfb1-2 differ in sequences in the aromatic domain and the proline rich repeat region, whereas the fibronectin binding region was conserved and exhibited similar fibronectin binding activity. The presence of Sfb1-2 in emm1-2 strains was concomitant with significantly higher fibronectin-binding and invasion efficiency of HEp-2 cells when compared to emm1 isolates. The role of Sfb1-2 in invasion was confirmed by latex bead assay. emm1-2 isolates follow membrane ruffling mechanism during invasion and intracellularly follow classical endocytic pathway. Further studies are required to understand the correlation between the presence of emm1-2 isolates and the disease pattern in North India.

Intrinsic antiferromagnetic/insulating phase at manganite surfaces and interfaces.

In this work we investigate interfacial effects in bilayer systems integrated by La(2/3)Sr(1/3)MnO(3) (LSMO) thin films and different capping layers by means of surface-sensitive synchrotron radiation techniques and transport measurements. Our data reveal a complex scenario with a capping-dependent variation of the Mn oxidation state by the interface. However, irrespective of the capping material, an antiferromagnetic/insulating phase is also detected at the interface, which is likely to originate from a preferential occupancy of Mn 3d 3z(2)-r(2) e(g) orbitals. This phase, which extends approximately to two unit cells, is also observed in uncapped LSMO reference samples, thus pointing to an intrinsic interfacial phase separation phenomenon, probably promoted by the structural disruption and inversion symmetry breaking at the LSMO free surface/interface. These experimental observations strongly suggest that the structural disruption, with its intrinsic inversion symmetry breaking at the LSMO interfaces, plays a major role in the observed depressed magnetotransport properties in manganite-based magnetic tunneling junctions and explains the origin of the so-called dead layer.

Development of the Nursing Community Apgar Questionnaire (NCAQ): a rural nurse recruitment and retention tool.

INTRODUCTION: Health professional shortages are a significant issue throughout the USA, particularly in rural communities. Filling nurse vacancies is a costly concern for many critical access hospitals (CAH), which serve as the primary source of health care for rural communities. CAHs and rural communities have strengths and weaknesses that affect their recruitment and retention of rural nurses. The purpose of this study was to develop a tool that rural communities and CAHs can utilize to assess their strengths and weaknesses related to nurse recruitment and retention. METHODS: The Nursing Community Apgar Questionnaire (NCAQ) was developed based on an extensive literature review, visits to multiple rural sites, and consultations with rural nurses, rural nurse administrators and content experts. RESULTS: A quantitative interview tool consisting of 50 factors that affect rural nurse recruitment and retention was developed. The tool allows participants to rate each factor in terms of advantage and importance level. The tool also includes three open-ended questions for qualitative analysis. CONCLUSIONS: The NCAQ was designed to identify rural communities' and CAHs' strengths and challenges related to rural nurse recruitment and retention. The NCAQ will be piloted and a database developed for CAHs to compare their results with those in the database. Furthermore, the NCAQ results may be utilized to prioritize resource allocation and tailor rural nurse recruitment and retention efforts to highlight a community's strengths. The NCAQ will function as a useful real-time tool for CAHs looking to assess and improve their rural nurse recruitment and retention practices and compare their results with those of their peers. Longitudinal results will allow CAHs and their communities to evaluate their progress over time. As the database grows in size, state, regional, and national results can be compared, trends may be discovered and best practices identified.

Parimagnetism in HoCo2 and TmCo2.

X-ray magnetic circular dichroism (XMCD), longitudinal (χac) and transverse (TS) ac magnetic susceptibility have been measured in the RCo2 series (R = Ho, and Tm) as a function of temperature and applied magnetic field. We show that parimagnetism is a general behavior among the RCo2 ferrimagnetic series (R being a heavy rare-earth ion). XMCD results supply evidence of the presence of two compensation temperatures above Tc, defining two different parimagnetic configurations, which is a fully unexpected result. The inverse χ'ac curve exhibits a small anomaly which vanishes under low applied magnetic fields. The combination of TS and XMCD measurements allows one to depict new magnetic phase diagrams for these compounds of the RCo2 series. A new scenario allowing one to understand the observed phenomenology as a Griffiths phase-like behavior is proposed, where the amorphous RCo2 represents the undiluted system case.

Factors that cause trimethoprim resistance in Streptococcus pyogenes.

The use of trimethoprim in treatment of Streptococcus pyogenes infections has long been discouraged because it has been widely believed that this pathogen is resistant to this antibiotic. To gain more insight into the extent and molecular basis of trimethoprim resistance in S. pyogenes, we tested isolates from India and Germany and sought the factors that conferred the resistance. Resistant isolates were identified in tests for trimethoprim or trimethoprim-sulfamethoxazole (SXT) susceptibility. Resistant isolates were screened for the known horizontally transferable trimethoprim-insensitive dihydrofolate reductase (dfr) genes dfrG, dfrF, dfrA, dfrD, and dfrK. The nucleotide sequence of the intrinsic dfr gene was determined for resistant isolates lacking the horizontally transferable genes. Based on tentative criteria, 69 out of 268 isolates (25.7%) from India were resistant to trimethoprim. Occurring in 42 of the 69 resistant isolates (60.9%), dfrF appeared more frequently than dfrG (23 isolates; 33.3%) in India. The dfrF gene was also present in a collection of SXT-resistant isolates from Germany, in which it was the only detected trimethoprim resistance factor. The dfrF gene caused resistance in 4 out of 5 trimethoprim-resistant isolates from the German collection. An amino acid substitution in the intrinsic dihydrofolate reductase known from trimethoprim-resistant Streptococcus pneumoniae conferred resistance to S. pyogenes isolates of emm type 102.2, which lacked other aforementioned dfr genes. Trimethoprim may be more useful in treatment of S. pyogenes infections than previously thought. However, the factors described herein may lead to the rapid development and spread of resistance of S. pyogenes to this antibiotic agent.