Sensibilidad de Escherichia coli frente a fosfomicina, en infecciones urinarias provenientes de personas con discapacidad que acudieron a la Secretaría Nacional por los Derechos Humanos de las Personas con Discapacidad-SENADIS / Susceptibility of Escherichia coli against fosfomycin in urinary tract infections from people with disabilities who attended SENADIS

INTRODUCCIÓN: Fosfomicina es un antimicrobiano de amplio espectro utilizado para el tratamiento de las infecciones urinarias bajas; tiene actividad sobre bacilos gramnegativos y cocos grampositivos, así también sobre microorganismos multirresistentes, además de ofrecer una alternativa terapéutica de administración vía oral en dosis única, alcanzando una efectividad de 90%. OBJETIVO: Conocer la sensibilidad in vitro de Escherichia coli frente a fosfomicina, en infecciones urinarias provenientes de personas con discapacidad. MATERIAL Y MÉTODO: Estudio observacional, descriptivo, prospectivo, en el que se incluyó un total de 273 muestras de urocultivo, de pacientes de ambos sexos que acudieron a SENADIS, y que en el momento de la consulta presentaban síntomas de infección del tracto urinario, por lo que se les solicitó el análisis de orina simple y cultivo. De las muestras procesadas en el laboratorio de microbiología, que fueron positivas con crecimiento bacteriano significativo, se procedió a la identificación bacteriana y a la realización del antibiograma según las recomendaciones de CLSI. RESULTADOS: De estas 273 muestras, 91 fueron positivas para diferentes uropatógenos, 62/91 (68%) resultaron ser E. coli. De estas cepas de E. coli, 59/62 (95%) mostraron sensibilidad in vitro a fosfomicina. Comentario: Aunque el número de muestra obtenido es pequeño y no extrapolable ampliamente, pretendemos extender el trabajo por un tiempo más para compararlo más adelante. CONCLUSIONES: Se observa que fosfomicina presenta buena actividad in vitro frente a cepas de E. coli aisladas de urocultivo, pudiendo representar una buena alternativa terapéutica a ser utilizada en la población en estudio.

BACKGROUND: Fosfomycin is a broad-spectrum antibiotic used for the treatment of lower urinary tract infections, it is active against gramnegative bacilli and grampositive cocci, as well as against multi-resistant microorganism, in addition to offering a therapeutic alternative for oral administration in a single dose, reaching an effectiveness of 90%. AIM: To study the susceptibility of Escherichia coli to fosfomycin in urinary tract infections, of isolated strains obtained from patients with disabilities. METHODS: It is an observational, descriptive, prospective study in which a total of 273 urine culture samples of patients of both sexes who attended the SENADIS were included, and who at the time of the consultation presented symptoms of urinary tract infection. The urine positive cultures with significant bacterial growth were performed to determine its bacterial identification and the antibiogram according to CLSI recommendations. RESULTS: Of these 273 samples, 91 samples were positive for different uropathogens, with 62/91 (68%) being positive for E. coli. Of these E. coli strains, 59/62 (95%) showed in vitro susceptibility to fosfomycin. Comment: Although the number of samples obtained is small and it cannot be extrapolated, we pretend to extend the work for a while longer to be able to compare it later. CONCLUSION: Fosfomycin has good activity in vitro against E. coli isolated from urine culture in our institution, representing a good alternative to be used in our study population

The Arylamidine T-2307 as a Novel Treatment for the Prevention and Eradication of Candida tropicalis Biofilms.

Candida tropicalis is an emerging pathogen with a high mortality rate due to its virulence factors, including biofilm formation, that has important repercussions on the public health system. The ability of C. tropicalis to form biofilms, which are potentially more resistant to antifungal drugs and the consequent increasing antimicrobial resistance, highlights an urgent need for the development of novel antifungal. The present study analyzed the antibiofilm capacity of the arylamidine T-2307 on two strains of Candida tropicalis. Antimicrobial activity and time-killing assays were performed to evaluate the anticandidal effects of T-2307, the antibiofilm ability on biomass inhibition and eradication was evaluated by the crystal violet (CV) method. Furthermore, in Galleria mellonella infected larvae an increased survival after pre-and post- treatment with T-2307 was observed. The MTT test was used to determine the viability of immortalized human prostate epithelial cells (PNT1A) after exposure to different concentrations of T-2307. Levels of interleukin IL-4, IL-8, IL-10 were quantified after Candida infection of PNT1A cells and treatment. Active doses of T-2307 did not affect the viability of PNT1A cells, and drug concentrations of 0.005 or 0.01 µg mL-1 inhibited the secretion of inflammatory cytokines. Taken together, these results provide new information on T-2307, indicating this drug as a new and promising alternative therapeutic option for the treatment of Candida infections.

Ibrexafungerp Demonstrates In Vitro Activity against Fluconazole-Resistant Candida auris and In Vivo Efficacy with Delayed Initiation of Therapy in an Experimental Model of Invasive Candidiasis.

Candida auris is an emerging pathogen that has rapidly spread to many countries on multiple continents. Invasive infections caused by this species are associated with significant mortality, and treatment options are limited due to antifungal resistance. Ibrexafungerp is the first-in-class member of the triterpenoids, which inhibit the production of (1,3)-ß-d-glucan and can be administered orally. We evaluated the in vitro activity and in vivo efficacy of ibrexafungerp against C. auris Antifungal susceptibility was tested by broth microdilution against 54 C. auris isolates. Neutropenic mice were intravenously infected with a clinical isolate, and a 7-day treatment course was begun 24 h postinoculation with vehicle control, ibrexafungerp (20, 30, and 40 mg/kg orally twice daily), fluconazole (20 mg/kg orally once daily), or caspofungin (10 mg/kg intraperitoneally once daily). Fungal burden was assessed by colony counts in the kidneys on day 8 and on day 21 or as mice became moribund in the survival arm. Ibrexafungerp demonstrated consistent activity, with MICs ranging between 0.25 and 2 µg/ml against all isolates. Marked improvements in survival were observed in mice treated with the higher doses of ibrexafungerp and caspofungin. Similarly, reductions in kidney fungal burden were also observed in these groups. No improvements in survival or reductions in fungal burden were observed with fluconazole, consistent with the in vitro resistance of the isolate used to establish infection to this azole. These results demonstrate that ibrexafungerp is effective in vivo against C. auris even when the start of therapy is delayed.

Screening of antibacterial drugs for antimicrobial activity against Pythium insidiosum.

We tested 25 isolates of Pythium insidiosum to investigate their susceptibility to antibacterial drugs that act through inhibition of protein synthesis or other mechanisms of action. We observed that tetracycline, erythromycin, linezolid, nitrofurantoin, Synercid (quinupristin and dalfopristin), chloramphenicol, clindamycin, cetrimide, and crystal violet had inhibitory activity against P. insidiosum. Those in vitro results suggest that antibacterials that inhibit protein synthesis should be the primary antimicrobials investigated for the treatment of pythiosis in animals and humans.

The Fungal Cyp51-Specific Inhibitor VT-1598 Demonstrates In Vitro and In Vivo Activity against Candida auris.

Candida auris is an emerging pathogen associated with significant mortality and often multidrug resistance. VT-1598, a tetrazole-based fungal CYP51-specific inhibitor, was evaluated in vitro and in vivo against C. auris Susceptibility testing was performed against 100 clinical isolates of C. auris by broth microdilution. Neutropenic mice were infected intravenously with C. auris, and treatment began 24 h postinoculation with a vehicle control, oral VT-1598 (5, 15, and 50 mg/kg of body weight once daily), oral fluconazole (20 mg/kg once daily), or intraperitoneal caspofungin (10 mg/kg once daily), which continued for 7 days. Fungal burden was assessed in the kidneys and brains on day 8 in the fungal burden arm and on the days the mice succumbed to infection or on day 21 in the survival arm. VT-1598 plasma trough concentrations were also assessed on day 8. VT-1598 demonstrated in vitro activity against C. auris, with a mode MIC of 0.25 µg/ml and MICs ranging from 0.03 to 8 µg/ml. Treatment with VT-1598 resulted in significant and dose-dependent improvements in survival (median survival, 15 and >21 days for VT-1598 at 15 and 50 mg/kg, respectively) and reductions in kidney and brain fungal burden (reductions of 1.88 to 3.61 log10 CFU/g) compared to the control (5 days). The reductions in fungal burden correlated with plasma trough concentrations. Treatment with caspofungin, but not fluconazole, also resulted in significant improvements in survival and reductions in fungal burden compared to those with the control. These results suggest that VT-1598 may be a future option for the treatment of invasive infections caused by C. auris.

In Vivo Applicability of Neosartorya fischeri Antifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis.

As a consequence of emerging numbers of vulvovaginitis cases caused by azole-resistant and biofilm-forming Candida species, fast and efficient treatment of this infection has become challenging. The problem is further exacerbated by the severe side effects of azoles as long-term-use medications in the recurrent form. There is therefore an increasing demand for novel and safely applicable effective antifungal therapeutic strategies. The small, cysteine-rich, and cationic antifungal proteins from filamentous ascomycetes are potential candidates, as they inhibit the growth of several Candida spp. in vitro; however, no information is available about their in vivo antifungal potency against yeasts. In the present study, we investigated the possible therapeutic application of one of their representatives in the treatment of vulvovaginal candidiasis, Neosartorya fischeri antifungal protein 2 (NFAP2). NFAP2 inhibited the growth of a fluconazole (FLC)-resistant Candida albicans strain isolated from a vulvovaginal infection, and it was effective against both planktonic cells and biofilm in vitro We observed that the fungal cell-killing activity of NFAP2 is connected to its pore-forming ability in the cell membrane. NFAP2 did not exert cytotoxic effects on primary human keratinocytes and dermal fibroblasts at the MIC in vitro. In vivo murine vulvovaginitis model experiments showed that NFAP2 significantly decreases the number of FLC-resistant C. albicans cells, and combined application with FLC enhances the efficacy. These results suggest that NFAP2 provides a feasible base for the development of a fundamental new, safely applicable mono- or polytherapeutic topical agent for the treatment of superficial candidiasis.

Clinical features, antifungal susceptibility, and outcome of Candida guilliermondii fungemia: An experience in a tertiary hospital in mid-Taiwan.

BACKGROUNDS: Candida guilliermondii is rarely isolated from clinical specimen. C. guilliermondii fungemia is seldom reported in the literature. The aims of this study were to report the clinical features, antifungal susceptibility, and outcomes of patients with C. guilliermondii fungemia. METHODS: From 2003 to 2015, we retrospectively analyzed the clinical and laboratory data of patients with C. guilliermondii fungemia in a tertiary hospital in mid-Taiwan. We performed a multivariable logistic regression analysis to identify the risk factors of mortality. The Sensititre YeastOne microtiter panel assessed the susceptibility of antifungal agents. RESULTS: In this study, we identified 36 patients with C. guilliermondii fungemia. The median age of patients was 50.5 years (range, 17 days to 96 year) and 20 cases (56%) were male. The incidence of C. guilliermondii fungemia was 0.05 per 1000 admissions. Malignancy was the most common co-morbidity, and 25 (69%) patients had central venous catheter in place. Thirty-day overall mortality was 16.7%. In multivariate logistical regression analysis, catheter retention was an independent risk factor of mortality. According to epidemiological cutoff values, most clinical isolates (21/22, 95.5%) belonged to the wild-type MIC distributions for amphotericin B and flucytosine; however, the isolates were less susceptible to fluconazole (68%) and echinocandins (77-91%). CONCLUSION: Despite the lower mortality rate associated with C. guilliermondii fungemia, the removal of a central venous catheter remained an independent factor influencing the outcome of patients. The clinical significance of less susceptibility of C. guilliermondii to triazoles and echinocandins remains to be elucidated.

Successful therapy in unusual generalized Dermatophilus congolensis infection in a calf based on modified in vitro disk diffusion test / Sucesso no tratamento de infecção generalizada em bezerra por Dermatophilus congolensis baseado em teste in vitro modificado de difusão com discos

Bovine dermatophilosis is a dermatitis characterized by typical focal or localized lesions with "paintbrush" aspect and occasionally as disseminated cutaneous disease. We report the case of a one-year-old Nelore female with history of chronic cutaneous disseminated lesions that appeared immediately after a rainfall period. Serous to purulent exudates, hair with tufted appearance, hyperkeratotic, non-pruritic, hardened, yellowish to brown, and coalescent crusty lesions were observed distributed all over its body. Removal of the crusts revealed ulcerated or hemorrhagic areas, with irregular elevated crusts like "paintbrush". Microbiological diagnosis enabled the identification of a microorganism, the Dermatophilus congolensis. Despite disseminated and chronic lesions, we obtained a successful therapy with parenteral therapy using long-acting tetracycline based on modified in vitro disk diffusion test. The present report highlights success therapy in uncommon generalized bovine dermatophilosis with selection of first-choice drugs based on modified in vitro susceptibility test, and need of responsible use of antimicrobials in livestock.(AU)

A dermatofilose bovina é uma dermatite caracterizada por lesões focais ou localizadas com aspecto de "pincel" e, ocasionalmente, como lesão cutânea disseminada. Relata-se o caso de uma fêmea bovina de um ano de idade, que foi atendida apresentando história de lesões cutâneas crônicas imediatamente após um período de alta pluviosidade. Ao exame clínico, lesões serosas a purulentas, com hiperqueratose, coalescentes, não pruriginosas, ressecadas, de coloração amarelada à acinzentada foram observadas distribuídas de modo generalizado pelo animal. A remoção das crostas revelou áreas ulceradas ou hemorrágicas, com crostas irregulares e elevadas semelhantes a "pincel". O diagnóstico microbiológico possibilitou a identificação do micro-organismo Dermatophilus congolensis. Apesar das lesões disseminadas e crônicas, a cura do animal foi obtida com tratamento parenteral usando oxitetraciclina de longa duração, baseado em teste in vitro de sensibilidade microbiana modificado. O presente relato ressalta o sucesso no tratamento de caso incomum de lesões generalizadas de dermatofilose bovina com respaldo de teste in vitro de sensibilidade modificado, bem como a necessidade do uso responsável de antimicrobianos em animais de produção.(AU)

Efficacy of oleylphosphocholine (OlPC) in vitro and in a mouse model of invasive aspergillosis.

Invasive aspergillosis (IA) has become increasingly common and is characterised by high morbidity and mortality. Upcoming resistance threatens treatment with azoles and highlights the continuous need for novel therapeutics. This laboratory study investigated the in vitro and in vivo potential of the alkylphospholipid oleylphosphocholine (OlPC) against Aspergillus. In vitro activities of OlPC, miltefosine, posaconazole and voriconazole were determined for Aspergillus fumigatus, A. niger, A. terreus and A. flavus. In vivo efficacy of OlPC was evaluated in a systemic A. fumigatus mouse model, adopting a short-term and long-term oral or intraperitoneal dosing regimen. OlPC showed good in vitro activity against A. fumigatus (IC50 = 1.04 µmol l(-1)). Intraperitoneal administration of 50 mg kg(-1) day(-1) OlPC significantly reduced the fungal organ burdens at 4 days post-infection (dpi). Although 5- and 10-day OlPC treatment improved survival, organ burdens were not affected at 10 and 15 dpi. While this study showed excellent in vitro activity of OlPC against Aspergillus spp., its therapeutic efficacy in an acute mouse model for IA was less convincing. Given the limited therapeutic options in the current antifungal market for invasive infections, OlPC activity should be assessed in a less stringent in vivo model, potentially in combination treatment with other already marketed antifungal drugs.

Clinical and mycological evaluation of an herbal antifungal formulation in canine Malassezia dermatitis.

OBJECTIVE: Malassezia pachydermatis is a common cause of more widespread dermatitis in dogs (CMD). Recurrences are common, and this disorder can be very troubling for both dogs and for the pet owner. MATERIAL AND METHODS: The treatment of 20 dogs affected by dermatitis due to M. pachydermatis, with Malacalm(®), a commercially available mixture consisting of essential oils (Citrus aurantium 1%, Lavandula officinalis 1%, Origanum vulgare 0.5%, Origanum majorana 0.5%, Mentha piperita 0.5% and Helichrysum italicum var. italicum 0.5%, in sweet almond oil and coconut oil) is reported. The effectiveness of the whole mixture, of component essential oils and of their more represented compounds against clinical isolates was evaluated by a microdilution test. Twenty animals were topically administered the mixture twice daily for 1 month. Ten animals were treated with a conventional therapy based on ketoconazole 10mg/kg/day and chlorhexidine 2% twice a week for 3 weeks. At the end of both treatments animals significantly improved their clinical status. Adverse effects were never noticed. Follow-up visit performed on day 180th allowed to observe a recurrence of clinical signs in all the subjects treated conventionally, while not significant clinical changes were referred in dogs treated with Malacalm(®). The overall MIC value of Malacalm(®) was 0.3%. O. vulgare showed the lowest minimum inhibitory concentrations (MIC), being active at 0.8%, followed by M. piperita (1%), O. majorana (1.3%), C. aurantium (2%) and L. officinalis (4%) while H. italicum did not yield any antimycotic effect up to 10%. Active major compounds were thymol, carvacrol, p-cymene, 1,8-cineol, limonene and menthol. CONCLUSION: The phytotherapic treatment achieved a good clinical outcome, and no recurrence of skin disorders on day 180th was recorded. This herbal remedium appeared to be a safe tool for limiting recurrences of CMD.

A breach in patients' safety in randomized controlled trials of antibiotic drugs.

In a number of randomized controlled trials of antibiotic drugs the pathogens cultured from patients and their in vitro susceptibilities to the study drugs were not disclosed to the physicians during the whole course of the disease. These trials included patients with sepsis and bacteraemia. In clinical practice the information on the pathogen and its susceptibilities serves to re-evaluate the antibiotic treatment on the second or third day. As there is strong evidence that antibiotic treatment (empirical and definitive) matching the in vitro susceptibility of the pathogen reduces fatality rates in severe infections, withholding these data is a breach in patient safety. Sponsors and investigators of clinical trials of antibiotic drugs should ensure that the susceptibility of pathogens to the trial drugs are made available to clinicians in real time and taken into account when considering change in patient management, as would be the case in routine clinical practice. Members of research ethics committees should make sure that the protocols provide for this, while journals considering publication of clinical trial results should ask that details on the availability of susceptibilities to the trial antibiotics are disclosed in the methods section.

Susceptibilidad a la nistatina de aislamientos bucales de Candida y su correlación con la respuesta al tratamiento / Susceptibility to nystatin of oral Candida isolates and its correlation with the response to treatment

INTRODUCCIÓN: la candidiasis bucofaríngea es un marcador precoz de progresión a sida en los pacientes seropositivos al VIH sin tratamiento antirretroviral, así como un indicador de no adherencia al tratamiento antirretroviral o su posible fracaso. OBJETIVO: determinar la susceptibilidad frente a nistatina de las cepas de Candida aisladas de la cavidad bucal de pacientes seropositivos al VIH, y correlacionar los resultados con la respuesta al tratamiento. MÉTODOS: se realizó un estudio de susceptibilidad in vitro frente a nistatina para 104 cepas aisladas de lesiones de candidiasis bucofaríngea de 97 pacientes VIH/sida que habían participado, como voluntarios, en un ensayo clínico para evaluar la respuesta a cuatro drogas. De los 104 aislamientos, 58 fueron obtenidos antes de iniciar los esquemas de tratamientos y 46 una vez finalizado estos. Se procedió según el micrométodo el documento M27-A3 del Clinical and Laboratory Standards Institute. RESULTADOS: todas las cepas se comportaron como sensibles a la nistatina, con valores de concentración mínima inhibitoria (CMI) menores que 16 µg/mL, independientemente del momento de su aislamiento y de la droga administrada a los pacientes. En el grupo de pacientes tratados con nistatina, los rangos de CMI80 (1-2 µg/mL), las medias geométricas y los valores acumulativos de la droga frente a los aislamientos de Candida albicans obtenidos antes de iniciar el tratamiento, resultaron similares a los obtenidos frente a las cepas recobradas al finalizar este. De todas las especies identificadas, C. lusitaniae fue la que alcanzó el valor absoluto de CMI más elevado, 4 µg/mL. CONCLUSIONES: la correlación entre la evolución clínica de los pacientes y los resultados de los estudios de susceptibilidad de sus aislamientos in vitro, fue buena para los pacientes con evolución favorable, pero no para predecir posibles fracasos terapéuticos.

INTRODUCTION: oropharyngeal candidiasis is an early marker of progression to AIDS in HIV-positive patients and an indicator of non-adherence of treatment or possible failure in patients undergoing anti-retroviral therapy. OBJECTIVE: to determine the in vitro susceptibility to nystatin in Candida strains isolated from the oral cavity of HIV-positive patients, and to correlate the results with the response to treatment. METHODS: a study of in vitro susceptibility to nystatin was conducted in 104 oral isolates from 97 HIV/AIDS patients, who participated as volunteers in a clinical trial to evaluate the response to four antifungal drugs. Fifty-eight of the 104 isolates were obtained before starting treatment and the remaining 46 at the end of therapy. Broth microdilution method was performed according to the document M27-A3 of the Clinical and Laboratory Standards Institute. RESULTS: one hundred percent of the strains were susceptible to nystatin, with minimum inhibitory concentration (MIC) values of <16 µg/mL, regardless of the time of isolation and of the drug administered to patients. In the group of patients treated with nystatin, the MIC80 ranges (1-2 µg/mL), geometric mean and cumulative values of the drug against Candida albicans isolates before starting treatment were similar to those obtained against strains recovered at the end. Among the identified species, C. lusitaniae reached the highest absolute MIC value (4 µg/mL). CONCLUSIONS: the correlation between the clinical evolution and the results of in vitro susceptibility tests was good in patients with a favorable outcome; however, it did not allow predicting possible treatment failure.