[Recurrent tinea corporis generalisata due to Terbinafine-resistant Trichophyton rubrum strain : Long-term treatment with super bioavailability itraconazole]. / Rezidivierende Tinea corporis generalisata durch einen Terbinafin-resistenten Trichophyton-rubrum-Stamm : Langzeitbehandlung mit Super-Bioavailability-Itraconazol.

For more than 30 years, an 82-year-old man has been suffering from tinea corporis generalisata in the sense of Trichophyton rubrum syndrome. The patient received long-term treatment with terbinafine. Fluconazole had no effect. There was an increase in liver enzymes with itraconazole. Super bioavailability (SUBA) itraconazole was initially not tolerated. A therapy attempt with voriconazole was successful, but was stopped due to side effects. The Trichophyton (T.) rubrum strain isolated from skin scales was tested for terbinafine resistance using the breakpoint method and found to be (still) sensitive. Sequencing of the squalene epoxidase (SQLE) gene revealed a previously unknown point mutation of the codon for isoleucine ATC→ACC with amino acid substitution I479T (isoleucine479 threonine). Long-term therapy with terbinafine 250 mg had been given every 3 days since 2018. In addition, bifonazole cream, ciclopirox solution, and occasionally terbinafine cream were used. The skin condition was stable until an exacerbation of the dermatophytosis in 2021. There were erythematosquamous, partly atrophic, centrifugal, scaly, confluent plaques on the integument and the extremities. Fingernails and toenails had white to yellow-brown discoloration, and were hyperkeratotic and totally dystrophic. T. rubrum was cultured from skin scales from the integument, from the feet, from nail shavings from the fingernails and also toenails and detected by PCR. In the breakpoint test, the T. rubrum isolates from tinea corporis and nail samples showed a minimum inhibitory concentration (MIC) of 0.5 µg ml-1 (terbinafine resistance in vitro). Sequencing of the SQLE gene of the T. rubrum isolate revealed evidence of a further point mutation that led to amino acid substitution I479V (isoleucine 479 valine). Long-term therapy was started with SUBA itraconazole: 14 days 2â€¯× 1 capsule daily, then twice weekly administration of 2â€¯× 50 mg. During breaks in therapy, the mycosis regularly flared up again. Finally, 50 mg SUBA itraconazole was given 5 days a week, which completely suppressed the dermatophytosis. Topically, ciclopirox and miconazole cream were used alternately. In conclusion, in the case of recurrent and therapy-refractory dermatophytoses caused by T. rubrum, terbinafine resistance must also be considered in individual cases. An in vitro resistance test and point mutation analysis of the squalene epoxidase gene confirms the diagnosis. Itraconazole, also in the form of SUBA itraconazole, is the drug of choice for the oral antifungal treatment of these patients.

Adaptive Laboratory Evolution of Staphylococcus aureus Resistance to Vancomycin and Daptomycin: Mutation Patterns and Cross-Resistance.

Vancomycin and daptomycin are first-line drugs for the treatment of complicated methicillin-resistant Staphylococcus aureus (MRSA) infections, including bacteremia. However, their effectiveness is limited not only by their resistance to each antibiotic but also by their associated resistance to both drugs. It is unknown whether novel lipoglycopeptides can overcome this associated resistance. Resistant derivatives from five S. aureus strains were obtained during adaptive laboratory evolution with vancomycin and daptomycin. Both parental and derivative strains were subjected to susceptibility testing, population analysis profiles, measurements of growth rate and autolytic activity, and whole-genome sequencing. Regardless of whether vancomycin or daptomycin was selected, most of the derivatives were characterized by a reduced susceptibility to daptomycin, vancomycin, telavancin, dalbavancin, and oritavancin. Resistance to induced autolysis was observed in all derivatives. Daptomycin resistance was associated with a significant reduction in growth rate. Resistance to vancomycin was mainly associated with mutations in the genes responsible for cell wall biosynthesis, and resistance to daptomycin was associated with mutations in the genes responsible for phospholipid biosynthesis and glycerol metabolism. However, mutations in walK and mprF were detected in derivatives selected for both antibiotics.

In Vitro Selection of Enterobacter cloacae with Cefepime, Meropenem, and Ceftazidime-Avibactam Generates Diverse Resistance Mechanisms.

Five Enterobacter cloacae isolates were subjected to 10-day serial passage in broth microdilution with cefepime, meropenem, or ceftazidime-avibactam to evaluate increases in minimum inhibitory concentration (MIC) and resistance mechanisms after exposure. Post-exposure isolates displaying >2-fold changes from the parent isolate were analysed alongside the parent isolate. Increases in MIC were 4- to 256-fold (median: 16-fold) after cefepime exposure, 16- to 128-fold (64-fold) after meropenem, and 2- to 32-fold (8-fold) after ceftazidime-avibactam. Post-exposure isolates had diverse mechanisms, identified using a combination of short and long whole-genome sequencing. All agents selected for AmpC alterations in one isolate set. OmpC and TetA/AcrR regulator alterations were noted in meropenem and ceftazidime-avibactam post-exposure isolates of the same set. Other mutations in AmpC were noted when isolates were exposed to cefepime or ceftazidime-avibactam. A premature stop codon in the cell division inhibitor protein, MioC was observed when one parent isolate was exposed to any of the agents, indicating a cell persistence mechanism. Mutations in less common transporter systems and protein synthesis components were also noted. All agents showed cross-resistance to other ß-lactams and resistance mechanisms were diverse, with some not usually associated with ß-lactam resistance in Enterobacterales. This initial evaluation indicates that cefepime and meropenem select for isolates with higher MIC values compared to ceftazidime-avibactam. Further studies evaluating these findings should be performed for other species for which the primary ß-lactam resistance mechanism is not gene acquisition. These studies should evaluate these observations in vivo to assess their translation into patient treatment policies.

Aspergillus terreus Species Complex.

Infections due to Aspergillus species are an acute threat to human health; members of the Aspergillus section Fumigati are the most frequently occurring agents, but depending on the local epidemiology, representatives of section Terrei or section Flavi are the second or third most important. Aspergillus terreus species complex is of great interest, as it is usually amphotericin B resistant and displays notable differences in immune interactions in comparison to Aspergillus fumigatus. The latest epidemiological surveys show an increased incidence of A. terreus as well as an expanding clinical spectrum (chronic infections) and new groups of at-risk patients being affected. Hallmarks of these non-Aspergillus fumigatus invasive mold infections are high potential for tissue invasion, dissemination, and possible morbidity due to mycotoxin production. We seek to review the microbiology, epidemiology, and pathogenesis of A. terreus species complex, address clinical characteristics, and highlight the underlying mechanisms of amphotericin B resistance. Selected topics will contrast key elements of A. terreus with A. fumigatus. We provide a comprehensive resource for clinicians dealing with fungal infections and researchers working on A. terreus pathogenesis, aiming to bridge the emerging translational knowledge and future therapeutic challenges on this opportunistic pathogen.

De Novo Resistance to Arg10-Teixobactin Occurs Slowly and Is Costly.

Bacterial pathogens are rapidly evolving resistance to all clinically available antibiotics. One part of the solution to this complex issue is to better understand the resistance mechanisms to new and existing antibiotics. Here, we focus on two antibiotics. Teixobactin is a recently discovered promising antibiotic that is claimed to "kill pathogens without detectable resistance" (L. L. Ling, T. Schneider, A. J. Peoples, A. L. Spoering, et al., Nature 517:455-459, 2015, https://doi.org/10.1038/nature14098). Moenomycin A has been extensively used in animal husbandry for over 50 years with no meaningful antibiotic resistance arising. However, the nature, mechanisms, and consequences of the evolution of resistance to these "resistance-proof" compounds have not been investigated. Through a fusion of experimental evolution, whole-genome sequencing, and structural biology, we show that Staphylococcus aureus can develop significant resistance to both antibiotics in clinically meaningful timescales. The magnitude of evolved resistance to Arg10-teixobactin is 300-fold less than to moenomycin A over 45 days, and these are 2,500-fold and 8-fold less than evolved resistance to rifampicin (control), respectively. We have identified a core suite of key mutations, which correlate with the evolution of resistance, that are in genes involved in cell wall modulation, lipid synthesis, and energy metabolism. We show the evolution of resistance to these antimicrobials translates into significant cross-resistance against other clinically relevant antibiotics for moenomycin A but not Arg10-teixobactin. Lastly, we show that resistance is rapidly lost in the absence of antibiotic selection, especially for Arg10-teixobactin. These findings indicate that teixobactin is worth pursuing for clinical applications and provide evidence to inform strategies for future compound development and clinical management.

Insights Into the Resistome of Bovine Clinical Mastitis Microbiome, a Key Factor in Disease Complication.

Bovine clinical mastitis (CM) is one of the most prevalent diseases caused by a wide range of resident microbes. The emergence of antimicrobial resistance in CM bacteria is well-known, however, the genomic resistance composition (the resistome) at the microbiome-level is not well characterized. In this study, we applied whole metagenome sequencing (WMS) to characterize the resistome of the CM microbiome, focusing on antibiotics and metals resistance, biofilm formation (BF), and quorum sensing (QS) along with in vitro resistance assays of six selected pathogens isolated from the same CM samples. The WMS generated an average of 21.13 million reads (post-processing) from 25 CM samples that mapped to 519 bacterial strains, of which 30.06% were previously unreported. We found a significant (P = 0.001) association between the resistomes and microbiome composition with no association with cattle breed, despite significant differences in microbiome diversity among breeds. The in vitro investigation determined that 76.2% of six selected pathogens considered "biofilm formers" actually formed biofilms and were also highly resistant to tetracycline, doxycycline, nalidixic acid, ampicillin, and chloramphenicol and remained sensitive to metals (Cr, Co, Ni, Cu, Zn) at varying concentrations. We also found bacterial flagellar movement and chemotaxis, regulation and cell signaling, and oxidative stress to be significantly associated with the pathophysiology of CM. Thus, identifying CM microbiomes, and analyzing their resistomes and genomic potentials will help improve the optimization of therapeutic schemes involving antibiotics and/or metals usage in the prevention and control of bovine CM.

Punctual mutations in 23S rRNA gene of clarithromycin-resistant Helicobacter pylori in Colombian populations.

AIM: To characterize punctual mutations in 23S rRNA gene of clarithromycin-resistant Helicobacter pylori (H. pylori) and determine their association with therapeutic failure. METHODS: PCR products of 23S rRNA gene V domain of 74 H. pylori isolates; 34 resistant to clarithromycin (29 from a low-risk gastric cancer (GC) population: Tumaco-Colombia, and 5 from a high-risk population: Tuquerres-Colombia) and 40 from a susceptible population (28 from Tumaco and 12 from Túquerres) were sequenced using capillary electrophoresis. The concordance between mutations of V domain 23S rRNA gene of H. pylori and therapeutic failure was determined using the Kappa coefficient and McNemar's test was performed to determine the relationship between H. pylori mutations and clarithromycin resistance. RESULTS: 23S rRNA gene from H. pylori was amplified in 56/74 isolates, of which 25 were resistant to clarithromycin (20 from Tumaco and 5 from Túquerres, respectively). In 17 resistant isolates (13 from Tumaco and 4 from Túquerres) the following mutations were found: A1593T1, A1653G2, C1770T, C1954T1, and G1827C in isolates from Tumaco, and A2144G from Túquerres. The mutations T2183C, A2144G and C2196T in H. pylori isolates resistant to clarithromycin from Colombia are reported for the first time. No association between the H. pylori mutations and in vitro clarithromycin resistance was found. However, therapeutic failure of eradication treatment was associated with mutations of 23S rRNA gene in clarithromycin-resistant H. pylori (κ = 0.71). CONCLUSION: The therapeutic failure of eradication treatment in the two populations from Colombia was associated with mutations of the 23S rRNA gene in clarithromycin-resistant H. pylori.

Fitness Cost of Daptomycin-Resistant Staphylococcus aureus Obtained from in Vitro Daptomycin Selection Pressure.

Daptomycin-resistant (DAP-R) Staphylococcus aureus strains are well documented, but have not been reported in China. To elucidate the evolution adaptability and fitness cost of DAP-R S. aureus, three DAP susceptible strains, Pre3 (MRSA, ST239-t037), Pre5 (MRSA, ST239-t037), and Pre14b (MSSA, ST188-t189), were isolated from patients with bloodstream infections, and serially passaged in Mueller-Hinton broth with a gradient of DAP concentration to select for resistance. Highly DAP-R mutants were obtained after screening for 34 passages. The DAP minimum inhibitory concentrations increased from 0.5 µg/ml in the parent strains to 16 µg/ml in the mutants, which remained tolerant to 4 µg/ml of DAP for more than 160 generations. The growth of the three mutant strains was slower than that of the parent strains, with relative fitness cost of 34.8%, 19.2%, and 15.0%, respectively. The in vitro serum tolerance of the mutants was decreased, and the lethality and pathogenicity in mice were weakened (P < 0.01). Transmission electron microscopy found that the cell walls of the mutants were significantly thicker (from 38.6% to 75.4%) than those of the parent cells. Mutation L826F of mprF was found in Post14b, G299V, and L473I of mprF and Y225N of walK were found in Post3, while T345A of mprF, S52N of graS, and F473I of walK were found in Post5. Thus, stable DAP-R mutants could be obtained from a middle-short term of in vitro DAP selection, and according to their fitness cost, some prevention and control work may be done to cope with DAP-R S. aureus that may appear in China in the future.

Comparison of the risk of acquiring in vitro resistance to doripenem and tazobactam/piperacillin by CTX-M-15-producing Escherichia coli.

To compare the risk of acquiring in vitro resistance between doripenem and tazobactam/piperacillin by CTX-M-15-producing Escherichia coli, the in vitro frequency of resistance was determined. Four strains carrying multiple ß-lactamases such as blaOXA-1 or blaCTX-M-27 as well as blaCTX-M-15 and blaTEM-1 were used. No resistant colonies appeared on doripenem-containing plates, whereas resistant colonies were obtained from three of four test strains against tazobactam/piperacillin using agar plate containing 8- to 16-fold MIC of each drug. These three acquired tazobactam/piperacillin-resistant strains were not cross-resistant to doripenem, and they showed 1.9- to 3.1-fold higher piperacillin-hydrolysis activity compared to those of each parent strain. The change of each ß-lactamase mRNA expression measured by real-time PCR varied among three resistant strains. One of three tazobactam/piperacillin-resistant strains with less susceptibility to ceftazidime overexpressed both blaCTX-M-15 and blaTEM-1, and the other two strains showed higher mRNA expression of either blaTEM-1 or blaOXA-1. These results demonstrate that multiple ß-lactamases carried by CTX-M-15-producing E. coli contributed to the resistance to tazobactam/piperacillin. On the other hand, these resistant strains maintained susceptibility to doripenem. The risk of acquiring in vitro resistance to doripenem by CTX-M-15-producing E. coli seems to be lower than that to tazobactam/piperacillin.

Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis.

BACKGROUND: Improving our understanding of the relationship between the genotype and the drug resistance phenotype of Mycobacterium tuberculosis will aid the development of more accurate molecular diagnostics for drug-resistant tuberculosis. Studies that use direct genetic manipulation to identify the mutations that cause M. tuberculosis drug resistance are superior to associational studies in elucidating an individual mutation's contribution to the drug resistance phenotype. METHODS: We systematically reviewed the literature for publications reporting allelic exchange experiments in any of the resistance-associated M. tuberculosis genes. We included studies that introduced single point mutations using specialized linkage transduction or site-directed/in vitro mutagenesis and documented a change in the resistance phenotype. RESULTS: We summarize evidence supporting the causal relationship of 54 different mutations in eight genes (katG, inhA, kasA, embB, embC, rpoB, gyrA and gyrB) and one intergenic region (furA-katG) with resistance to isoniazid, the rifamycins, ethambutol and fluoroquinolones. We observed a significant role for the strain genomic background in modulating the resistance phenotype of 21 of these mutations and found examples of where the same drug resistance mutations caused varying levels of resistance to different members of the same drug class. CONCLUSIONS: This systematic review highlights those mutations that have been shown to causally change phenotypic resistance in M. tuberculosis and brings attention to a notable lack of allelic exchange data for several of the genes known to be associated with drug resistance.

Desenvolvimento de sorvete simbiótico de graviola ( Annona muricata L. ) com teor reduzido de gordura e avaliação da resistência gastrointestinal dos probióticos in vitro / Development of low-fat symbiotic graviola ( Annona muricata L. ) ice-cream and evaluation of the probiotics gastrointestinal in vitro resistance

O presente trabalho objetivou avaliar o efeito da adição de inulina (I) e a substituição parcial da gordura do leite (G) pelo concentrado de proteína de soro de leite (WPC) sobre a sobrevivência dos probióticos Lactobacillus acidophilus NCFM e Bifidobacterium animalis subsp. lactis HN019 em sorvete de graviola com teor reduzido de gordura, ao longo do período de armazenamento e frente às condições encontradas no trato gastrointestinal (TGI) simuladas in vitro. Adicionalmente, avaliou-se a influência desses ingredientes (6% I; 1,5% WPC; 3% e 1,5% G) sobre as características tecnológicas e a aceitabilidade do sorvete funcional. Empregou-se um planejamento fatorial 22, para 4 formulações produzidas, em triplicata, totalizando 12 ensaios: F1- controle (- I, - WPC); F2 (+ I, - WPC); F3 (- I, + WPC) e F4 (+ I, + WPC). Todas as formulações foram armazenadas a -18±3ºC e avaliadas após 2, 28, 56, 84 e 112 dias de armazenamento. A determinação das características tecnológicas foi realizada com as análises de dureza instrumental (em analisador de textura TA-XT2), fração de derretimento, overrun (durante a elaboração do produto) e perfil lipídico. Para o teste de aceitabilidade do produto, utilizou-se uma escala hedônica estruturada de 9 pontos. Elevada viabilidade probiótica foi observada para todas as formulações, com médias de populações acima de 8,0 log UFC/g, não diferindo significativamente durante o armazenamento de 112 dias (p>0,05). B. animalis subsp. lactis HN019 apresentou uma maior resistência em relação a L. acidophilus NCFM quando submetido aos sucos gastrointestinais artificiais, uma vez que a população de NCFM e de HN019 diminuíram, respectivamente, cerca de 5,2 log UFC/g e de 1,2 log UFC/g, durante o armazenamento. O efeito protetor do WPC e/ou I sobre a resistência de L. acidophilus aos sucos gastrointestinais artificiais foi observada no 56º dia e, para B. animalis subsp. lactis no 2º dia de armazenamento (p<0,05). Os sorvetes com WPC apresentaram menores valores de dureza, aos 7º e 112º dias de estocagem (p<0,05). A adição de inulina influenciou no aumento da dureza para F2 após 56 dias e para F4 durante todo período de armazenamento (p<0,05). Os resultados mostraram, também, que a presença do WPC e/ou inulina reduziu a velocidade de derretimento dos sorvetes durante todo o armazenamento (p<0,05). Elevados escores médios (entre 6,8 e 8,0) foram obtidos no teste de aceitabilidade sensorial dos sorvetes probióticos, indicando excelente aceitação pelos consumidores e não diferiram significativamente durante o armazenamento de até 84 dias. Já para F4, a adição do WPC + I aumentou a aceitação do produto após 56 dias (p<0,05). Os resultados obtidos sugerem que a utilização do WPC como substituto parcial da gordura láctea separadamente ou combinada com a inulina pode ser vantajosa no desenvolvimento de sorvete probiótico com baixo teor de gordura, uma vez que a presença desses ingredientes desempenhou um papel importante na proteção dos probióticos contra o efeito dos fluidos gastrointestinais nos testes in vitro. Além deste efeito protetor, a utilização da inulina e WPC também melhorou as características tecnológicas e sensoriais do sorvete funcional reduzido de gordura

This study aimed to assess the effect of the addition of inulin (I) and the partial substitution of the milk fat (MF) by whey protein concentrate (WPC) on Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis HN019 viability incorporated in low fat graviola (Annona muricata L.) ice-cream and on probiotic survival under in vitro simulated gastrointestinal conditions throughout 112 days of storage. Moreover, the influence of these ingredients (6% I; 1,5% WPC; 3% and 1,5% MF) on the functional ice-cream technological and sensorial features was also evaluated. Employing a 22 factorial design, four formulations were produced, in triplicates: F1- control (- I, - WPC); F2 (+ I, - WPC); F3 (- I, + WPC) and F4 (+ I, + WPC). The product were stored at -18±3ºC and analyzed after 2, 28, 56, 84, and 112 days of storage. Ice-creams from each trial were used for determination of L. acidophilus and B. animalis subsp. lactis viability in the products and survival in ice-creams submitted to gastrointestinal simulated conditions during storage at -18±3ºC for up to 112 days. For the determination of technological features, instrumental hardness (in TA-XT2 Texture Analyser), melting rate, overrun (during production), and lipid profile were determined. For sensory acceptability evaluation, a 9 point hedonic scale was used. High probiotic viability was observed for all formulations, with mean populations above 8.0 cfu/g and which did not differ significantly throughout 112 days of storage (p>0.05). B. animalis subsp. lactis HN019 resistance to the artificial gastrointestinal juices was higher than for L. acidophilus NCFM, since the NCFM and the HN019 populations decreased approximately 5.2 log cfu/g and 1.2 log cfu/g, respectively, throughout storage. The protective effect of WPC and/or WPC + I on the L. acidophilus resistance to artificial gastrointestinal juices was observed on the 56th day and for B. animalis subsp. lactis on the 2nd day of storage (p<0.05). The ice-creams with WPC presented lower hardness in the 7th and 112nd days of frozen storage (p<0.05). The addition of inulin led to an incresed hardnes for F2 after 56 days and for F4 during the whole storage (p<0.05). The results also showed that the presence of the WPC and/or inulin reduced the ice-creams melting rates during the whole storage (p<0.05). The high mean scores obtained (between 6.8 and 8.0) in the acceptability test indicated that the functional ice-creams evaluated were very well accepted, and did not differ significantly throughout storage of up to 84 days. Except for F4, the addition of the WPC + I improved the acceptability after 56th days of frozen storage (p<0.05). The results suggest that the use of WPC for the partial substitution of the milk fat separately or combined with inulin may be advantageous in the development of low-fat synbiotic ice-cream, since the presence of these ingredients played an important role in the probiotic protection against gastrointestinal juices in the in vitro simulated assays. Besides these protective effects, inulin and WPC also improved the technological and sensory features of the low-fat functional ice-cream

Susceptibilidad bacteriana a antimicrobianos: especies aisladas en pacientes ambulatorios de la Región Metropolitana, Chile, año 2007 / In vitro susceptibility patterns of bacterial species isolated in outpatients of the Metropolitan Región, Chile, year 2007

A partial surveillance of bacterial in vitro susceptibility to antibiotics, performed by a outpatient clinic, at Santiago, Chile, during year 2007, has yielded the following results: Staphylococcus aureus (n: 232) 3 percent of methicillin (oxacillin) resistance; Streptococcus pyogenes (n: 120) 6 percent of macrolides resistance; Haemophilus influenzae nt (n: 60) 12 percent of ampicillin and 3 percent of chloramphenicol resistance; Neisseria gonorrhoeae (n: 170): 78 percent of penicillin, 56 percent of tetracyclin and 32 percent of ciprofloxacin resistance; Escherichia coli obtained from uriñe: (adults n: 3.066, children n: 260) 27-28 percent of sulpha-trimethoprim resistance, 15 percent (children) -21 percent (adults) of cefadroxil resistance.

Una vigilancia parcial de la susceptibilidad bacteriana a antimicrobianos en la comunidad de Santiago, Chile, en el año 2007, efectuada por un centro de atención ambulatoria, ha dado las siguiente frecuencia de resistencia in vitro: Staphylococcus aureus (n: 232) 3 por ciento a meticilina (cloxacilina); Streptococcus pyogenes (n: 120) 6 por ciento a macrólidos; Haemophilus influenzae nt (n: 60) 12 por ciento a ampicilina y 3 por ciento a cloranfenicol; Neisseria gonorrhoeae (n: 170): 78 por ciento a penicilina, 56 por ciento a tetraciclina y 32 por ciento a ciprofloxacina; Escherichia coli uropatógenas: (adultos n: 3.066, niños n: 260) 27-28 por ciento a cotrimoxazol, 15 por ciento (niños) -21 por ciento (adultos) a cefadroxilo.

Susceptibilidad de levaduras vaginales a los antifúngicos más utilizados en Maringá, Paraná, Brasil / Susceptibility to vaginal yeast in most used antifungal in Maringá, Paraná, Brazil

Se determinó la susceptibilidad antifúngica in vitro de 78 cepas de levaduras aisladas de mujeres de la ciudad de Maringá/Paraná, Brasil, con candidiasis vulvovaginal (CVV), atendidas en el Laboratorio de Enseñanza e Investigación en Análisis Clínicos (LEPAC) de la Universidad Estatal de Maringá, desde el 1 de enero 2005 al 31 de diciembre 2006. Su sensibilidad in vitro fue investigada por el método de microdilución frente a ketoconazol (KETO), fluconazol (FLU), itraconazol (ITRA), nistatina (NIS) y anfotericina B (AMB). Para KETO, 41,5% de las cepas de C. albicans y 96% de Candida no-albicans presentaron resistencia (100% de C. glabrata) y para FLU solamente el 3,8% de los aislamientos de C. albicans y el 8,0% de C. glabrata fueron resistentes. Sólo 1,9% de las cepas de C. albicans y 20% de las de C. no-albicans fueron resistentes a ITRA y el 5,7% de las C. albicans y el 8% de las C. no-albicans (sólo C. glabrata) fueron resistentes a AMB. No hubo aislamientos resistentes a NIST, pero sí una elevada frecuencia de sensibilidad dosis dependiente "in vitro". Estos datos avalan la creciente necesidad de la realización de pruebas de identificación y susceptibilidad in vitro a los antifúngicos para establecer el correcto tratamiento de la CVV.

In vitro antifungal susceptibility was determined in the 78 yeasts isolated from patients with vulvovaginal candidiasis (VVC) from the city of Maringá/Parana/Brazil, assisted in the Laboratory of Teaching and Research in Clinical Analysis of the State University of Maringá, from 01 January 2005 to December 31, 2006. Its sensibility in vitro was tested according to microdilution method in front of ketoconazol (KETO), fluconazole (FLU), itraconazole (ITRA), nistatin (NIS) and amphotericin B (AMB). For KET, 41.5% of the C. albicans and 96.0% of the C. non-albicans showed resistance (100.0% of C. glabrata) and for FLU, only 3.8% of the isolates of C. albicans and 8.0% of C. glabrata showed resistance. Only 1.9% of the C. albicans and 20% of the C. no-albicans were resistant. For AMB, 5.7% of the C. albicans and 8% of the C. no-albicans (only C. glabrata), were resistant. There were no isolations resistant from NIST, however, there was a high frequency of dose-dependent sensibility (SDD) in vitro. These data makes it possible to confirm the growing necessity of the performance of identification tests and in vitro antifungal susceptibility to antifungals to establish the correct treatment of CVV.

Changing Trends in Antimicrobial Resistance Among Invasive Pneumococcal Pathogens in Asian Countries:Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study / 감염과화학요법

BACKGROUND: Emergence of pneumococcal resistance became a global issue since 1990s. According to the ANSORP studies with clinical isolates and carriage isolates between 1996 and 1999, some Asian countries showed alarmingly high prevalence of resistance to penicillin and other antimicrobial agents. To investigate the changing trends of pneumococcal resistance, ANSORP study group has performed a multinational surveillance study with invasive pneumococcal isolates from Asian countries. METHODS: All isolates from various invasive pneumococcal diseases were prospectively collected from 14 centers in 12 countries between November 1999 to August 2001. Broth microdilution tests with 16 antimicrobial agents were performed according to the NCCLS procedures. Serotyping was performed by means of Quelling reaction with use of group-specific antisera. RESULTS: A total of 685 isolates were collected. Overall, 52.4% of invasive isolates from Asian countries were not susceptible to penicillin (intermediate (I), 22.9%; Resistant (R), 29.5%). Vietnam showed the highest prevalence of penicillin non-susceptibility (I 20.6%, R 71.4%) followed by Sri Lanka (I 71.4%, R 14.3%), Hong Kong (I 24.1%, R 76%) and Korea (I 9.7%, R 54.8%). China (I 19.8%, R 23.4%) and Malaysia (I 9.1%, R 29.5%) also showed remarkable increase in penicillin resistance compared with previous ANSORP data, which were less than 10%. Vietnam (92.1%), Taiwan (87.7%), Korea (80.6%), and Hong Kong (76.8%) showed high prevalence of erythromycin resistance. MIC90s for ciprofloxacin were 4 microgram/mL (Hong Kong) and 2 microgram/mL (11 Asian countries except Hong Kong), respectively. CONCLUSION: Compared with previous data from ANSORP studies, antimicrobial resistance among invasive pneumococcal isolates has markedly increased in Vietnam, Sri Lanka, Taiwan, China, and Malaysia. Continuous surveillance of pneumococcal resistance in Asia is strongly warranted.

Changing Trends in Antimicrobial Resistance Among Invasive Pneumococcal Pathogens in Asian Countries:Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study / 감염과화학요법

BACKGROUND: Emergence of pneumococcal resistance became a global issue since 1990s. According to the ANSORP studies with clinical isolates and carriage isolates between 1996 and 1999, some Asian countries showed alarmingly high prevalence of resistance to penicillin and other antimicrobial agents. To investigate the changing trends of pneumococcal resistance, ANSORP study group has performed a multinational surveillance study with invasive pneumococcal isolates from Asian countries. METHODS: All isolates from various invasive pneumococcal diseases were prospectively collected from 14 centers in 12 countries between November 1999 to August 2001. Broth microdilution tests with 16 antimicrobial agents were performed according to the NCCLS procedures. Serotyping was performed by means of Quelling reaction with use of group-specific antisera. RESULTS: A total of 685 isolates were collected. Overall, 52.4% of invasive isolates from Asian countries were not susceptible to penicillin (intermediate (I), 22.9%; Resistant (R), 29.5%). Vietnam showed the highest prevalence of penicillin non-susceptibility (I 20.6%, R 71.4%) followed by Sri Lanka (I 71.4%, R 14.3%), Hong Kong (I 24.1%, R 76%) and Korea (I 9.7%, R 54.8%). China (I 19.8%, R 23.4%) and Malaysia (I 9.1%, R 29.5%) also showed remarkable increase in penicillin resistance compared with previous ANSORP data, which were less than 10%. Vietnam (92.1%), Taiwan (87.7%), Korea (80.6%), and Hong Kong (76.8%) showed high prevalence of erythromycin resistance. MIC90s for ciprofloxacin were 4 microgram/mL (Hong Kong) and 2 microgram/mL (11 Asian countries except Hong Kong), respectively. CONCLUSION: Compared with previous data from ANSORP studies, antimicrobial resistance among invasive pneumococcal isolates has markedly increased in Vietnam, Sri Lanka, Taiwan, China, and Malaysia. Continuous surveillance of pneumococcal resistance in Asia is strongly warranted.

Clinical Impact of Antimicrobial Resistance among Invasive Pneumococcal Pathogens in Asian Countries:Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study / 감염과화학요법

BACKGROUND: Despite the widespread emergence of antimicrobial resistance among pneumococcal strains worldwide, clinical implications of in vitro resistance still remain an open question. To evaluate the clinical impact of pneumococcal resistance in Asian countries where the prevalence of pneumococcal resistance was reported to be highest in the world, ANSORP has performed a prospective, multinational surveillance study with cases with invasive pneumococcal diseases in Asian countries. METHODS: In vitro susceptibility of pneumococcal isolates was determined by broth microdilution tests with 16 antimicrobial agents. All enrolled cases of pneumococcal infections were analyzed with regard to demographic data, clinical features, risk factors and mortality. RESULTS: A total of 646 patients with pneumococcal infections were enrolled from 14 centers in 12 countries between the period from November 1999 to August 2001. Pneumonia (58.4%) was the most common clinical disease followed by bacteremia (33.4%), otitis media (10.4%), and meningitis (10.2%). Among 646 isolates, 347 (53.7%) were penicillin non-susceptible (intermediate 23.1%, resistant 30.7%). MIC90s for penicillin ranged from 0.03 (India) to 4.0 microgram/mL (Korea, Taiwan, Vietnam, and Hong Kong). Overall mortality from pneumococcal diseases by penicillin non-susceptible strains was not different from that by susceptible strains. Pneumococcal pneumonia caused by penicillin- or erythromycin-resistant strains showed similar mortality, severity of illness, or complications to that by susceptible strains. Mortality from pneumococcal meningitis caused by penicillin non-susceptible strains was also similar to that by susceptible strains. CONCLUSION: Data suggest that current situation of in vitro resistance to penicillin or macrolides may not affect the mortality from pneumococal pneumonia or meningitis caused by antibiotic-resistant strains.

Clinical Impact of Antimicrobial Resistance among Invasive Pneumococcal Pathogens in Asian Countries:Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study / 감염과화학요법

BACKGROUND: Despite the widespread emergence of antimicrobial resistance among pneumococcal strains worldwide, clinical implications of in vitro resistance still remain an open question. To evaluate the clinical impact of pneumococcal resistance in Asian countries where the prevalence of pneumococcal resistance was reported to be highest in the world, ANSORP has performed a prospective, multinational surveillance study with cases with invasive pneumococcal diseases in Asian countries. METHODS: In vitro susceptibility of pneumococcal isolates was determined by broth microdilution tests with 16 antimicrobial agents. All enrolled cases of pneumococcal infections were analyzed with regard to demographic data, clinical features, risk factors and mortality. RESULTS: A total of 646 patients with pneumococcal infections were enrolled from 14 centers in 12 countries between the period from November 1999 to August 2001. Pneumonia (58.4%) was the most common clinical disease followed by bacteremia (33.4%), otitis media (10.4%), and meningitis (10.2%). Among 646 isolates, 347 (53.7%) were penicillin non-susceptible (intermediate 23.1%, resistant 30.7%). MIC90s for penicillin ranged from 0.03 (India) to 4.0 microgram/mL (Korea, Taiwan, Vietnam, and Hong Kong). Overall mortality from pneumococcal diseases by penicillin non-susceptible strains was not different from that by susceptible strains. Pneumococcal pneumonia caused by penicillin- or erythromycin-resistant strains showed similar mortality, severity of illness, or complications to that by susceptible strains. Mortality from pneumococcal meningitis caused by penicillin non-susceptible strains was also similar to that by susceptible strains. CONCLUSION: Data suggest that current situation of in vitro resistance to penicillin or macrolides may not affect the mortality from pneumococal pneumonia or meningitis caused by antibiotic-resistant strains.