scholarly journals Correlation ofIn VitroSusceptibility Based on MICs and Squalene Epoxidase Mutations with Clinical Response to Terbinafine in Patients with Tinea Corporis/Cruris

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Ananta Khurana ◽  
Aradhana Masih ◽  
Anuradha Chowdhary ◽  
Kabir Sardana ◽  
Sagar Borker ◽  
...  

ABSTRACTRecalcitrant dermatophytoses are on the rise in India. High MICs of terbinafine (TRB) and squalene epoxidase (SQLE) gene mutations conferring resistance inTrichophytonspp. have been recently documented. However, studies correlating laboratory data with clinical response to TRB in tinea corporis/cruris are lacking. For this study, we investigated the clinicomycological profile of 85 tinea corporis/cruris patients and performed antifungal susceptibility testing by CLSI microbroth dilution and SQLE mutation analysis of the isolates obtained and correlated these with the responses to TRB. Patients confirmed by potassium hydroxide (KOH) mounting of skin scrapings were started on TRB at 250 mg once a day (OD). If >50% clinical clearance was achieved by 3 weeks, the same dose was continued (group 1). If response was <50%, the dose was increased to 250 mg twice a day (BD) (group 2). If the response still remained below 50% after 3 weeks of BD, the patients were treated with itraconazole (ITR; group 3). Overall, skin scrapings from 64 (75.3%) patients yielded growth on culture. Strikingly, all isolates were confirmed to beTrichophyton interdigitaleisolates by internal transcribed spacer (ITS) sequencing. Thirty-nine (61%) of the isolates had TRB MICs of ≥1 µg/ml. Complete follow-up data were available for 30 culture-positive patients. A highly significant difference in modal MICs to TRB among the three treatment response groups was noted (P = 0.009). Interestingly, 8 of the 9 patients in group 3 harbored isolates exhibiting elevated TRB MICs (8 to 32 µg/ml) and SQLE mutations. The odds of achieving cure with TRB MIC < 1 µg/ml strains were 2.5 times the odds of achieving cure with the strain exhibiting MIC ≥1 µg/ml.

2018 ◽  
Author(s):  
Ananta Khurana ◽  
Aradhana Masih ◽  
Anuradha Chowdhary ◽  
Kabir Sardana ◽  
Sagar Borker ◽  
...  

ABSTRACTRecalcitrant dermatophytoses are on the rise and recent publications have documented high minimum inhibitory concentrations (MICs) to TRB and squalene epoxidase (SQLE) mutations. However, literature correlating the laboratory the data with clinical response is lacking.This study was conducted to study the clinico-mycological profile of tinea corporis and cruris, including antifungal susceptibility testing (AFST) and SQLE mutation analysis and correlate these with clinical response to TRB. Skin scrapings of patients with tinea corporis with/without tinea cruris were subjected to species identification, AFST and SQLE gene analysis (on 15 isolates). KOH confirmed cases were started on TRB 250mg once a day (OD). If >50% clinical clearance was achieved by 3 weeks; the same dose was continued.(Group 1). If clinical clearance at 3 weeks was <50%, the dose was increased to 250mg twice a day (BD) (Group 2). If the response still remained below 50% after 3 weeks of BD, the patients were treated with itraconazole (ITR)(Group 3). Trichophyton interdigitale was confirmed on all 64 isolates obtained on culture. Forty four (68.7%) isolates had high (≥1 μg/ml) MICs to TRB. Six isolates were found to have aminoacid substitution Leu393Phe in SQLE protein, while one had the substitution Phe397Leu. The difference in modal MICs to TRB between the 3 clinical response groups (1.5157μg/ml, 5.0396 μg/ml and 20.1587μg/ml respectively for group 1,2 and 3) was highly significant. Clinical response was achieved in 68% of those resistant by MIC data, and 42.8% of SQLE mutation harboring isolates, by increasing drug (TRB) exposure.We infer that TRB resistance in dermatophytes has reached alarming proportions in our patients. Though improved outcomes were achieved with higher drug exposure, with the high failure rate seen in the study, the case for shifting to another class of antifungals as first line agent against dermatophytoses is strong.


2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Ditte M. L. Saunte ◽  
Rasmus K. Hare ◽  
Karin M. Jørgensen ◽  
René Jørgensen ◽  
Mette Deleuran ◽  
...  

ABSTRACT In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported increasingly, particularly in India. We present 14 cases of terbinafine treatment failure in Trichophyton-infected Danish patients due to acquired resistance. Patients infected with Trichophyton rubrum (n = 12) or Trichophyton interdigitale (n = 2) with elevated terbinafine MICs during 2013–2018 were included. Antifungal susceptibility testing (AFST) was performed following a modified EUCAST E.Def 9.3.1 method (5 days of incubation) with or without cycloheximide and chloramphenicol (CC) supplementation of the growth medium. The squalene epoxidase (SE) target gene was sequenced, and 3-dimensional enzyme homology modeling was performed. Most patients (12/14 [86%]) were male. The mean age was 53.5 years (range, 11 to 77 years). The mean duration of infections was 4.8 years at the time of resistance detection. Prior systemic terbinafine treatment was documented for all patients, and topical therapy for 62% (information was missing in one case). Overall, nine isolates (64%) displayed high terbinafine resistance (MICs, 4 to >8 mg/liter), while two (14%) displayed moderate (MICs, 1 to 2 mg/liter) and three (21%) displayed low (MICs, 0.125 to 0.25 mg/liter) terbinafine resistance compared with control isolates. MICs generated with or without CC supplementation were similar, but CC prevented contamination. Known and novel SE amino acid substitutions (F397L, L393F, L393S, F415S, H440Y F484Y, and I121M V237I) were detected in resistant but not control isolates. Three-dimensional homology modeling suggested a role of the novel I121M and V237I alterations. Terbinafine resistance has been detected in Denmark using a modified EUCAST method, which facilitated susceptibility testing of dermatophytes. Action is needed for this emerging public health problem.


1997 ◽  
Vol 87 (2) ◽  
pp. 252-256 ◽  
Author(s):  
Gail D. Anderson ◽  
Yi-Xin Lin ◽  
Carrie Berge ◽  
George A. Ojemann

✓ Valproate (VPA) is associated with a variety of idiosyncratic hematological effects including thrombocytopenia, inhibition of platelet aggregation, and fibrinogen depletion. This has led some investigators to recommend discontinuation of VPA therapy prior to elective surgical procedures. However, administration of VPA therapy is not altered prior to surgery at the authors' center and no VPA-associated bleeding complications have been observed. Therefore, a retrospective chart review was conducted to verify the clinical observations in patients who had undergone cortical resection while receiving antiepileptic drugs (AEDs). Baseline, surgical, and postoperative laboratory data were available for a total of 313 patients, 111 of whom were receiving VPA and 202 of whom were receiving AEDs without VPA (control patients). Eighty-seven percent of the patients receiving VPA were also being treated with at least one other AED. The control group was approximately equally divided between monotherapy (55%) and polytherapy (45%) treatments. Platelet counts were significantly lower in the control polytherapy (284 ± 74 × 109/L) and both VPA groups (279 ± 113 × 109/L) as compared with the control monotherapy group (314 ± 85 × 109/L). Baseline fibrinogen levels were significantly lower in the VPA than in the control groups (223 ± 91 g/dl vs. 278 ± 95 g/dl). Both pre- and postoperatively, the VPA group had lower red blood cells counts, hematocrit, and hemoglobin levels. There was no significant difference between groups in estimated blood loss during surgery or qualitative wound discharge postsurgery. There was only one case of a bleeding complication, which occurred 14 days postoperatively in a patient receiving carbamazepine monotherapy. The results of this study confirm the clinical observations of an absence of bleeding complications in patients receiving VPA therapy at the time of surgery, despite differences in laboratory parameters.


2017 ◽  
Vol 8 (3) ◽  
pp. 465
Author(s):  
Nelly Indrasari ◽  
Purwati Purwati

<p>The case of maternal mortality in Bandar Lampung city in 2013 is 19 cases, in 2014 there are 7 cases and all died during childbirth and there are 19 cases of maternal death by 2015. (Profile of Lampung Province Health Office 2014). Research Objectives to Detect the Influence of Vulva Hygiene Technique on Number of Vulva Germs In Nifas Mother In BPM Bandar Lampung City Year 2016. This research method using quasi-experiment design. This study compares between treated groups and control groups. Treatment group 1 was treated with vulvar hygiene by using 1 cotton, group 2 using 3 kinds of cotton, group 3 using 5 cotton and control group without treatment. Population in this research is mother Nanyang checking his health at BPM in Bandar Lampung city at the time of research. The sample of respondent's research is 120. Data collection with Teradata is done as much as 1 time then done culture and examination in a local laboratory. Data were processed and analyzed by independent T-test. The result showed that the average number of germs was 2277,37 germs (95% CI 7140,59-38402,16) with standard deviation 65553,94 germs. The lowest number of germs and pathogen bacteria still 0.35% of respondents on the vulva hygiene of a cotton with a duration of 26 days. The result of analysis with cruciate Wallis test is 3,498. Looking at the statistics of the table by looking at the Chi-square table, for df (degrees of freedom)=3 and the significance level (α) = 5%, then obtained statist table 2.32. Because of the count statistic (2.32&gt; 0.321), then Ho accepted, or no significant difference (significant). The research unit can utilize and apply vulva hygiene technique with antiseptic, so it can prevent the occurrence of infection in the postpartum mother.</p>


2012 ◽  
Vol 57 (1) ◽  
pp. 382-389 ◽  
Author(s):  
Jorge Meneses Nunes ◽  
Fernando César Bizerra ◽  
Renata Carmona e Ferreira ◽  
Arnaldo Lopes Colombo

ABSTRACTRhodotorulaspecies are emergent fungal pathogens capable of causing invasive infections, primarily fungemia. They are particularly problematic in immunosuppressed patients when using a central venous catheter. In this study, we evaluated the species distribution of 51 clinical and 8 environmentalRhodotorulaspecies isolates using the ID32C system and internal transcribed spacer (ITS) sequencing. Antifungal susceptibility testing and biofilm formation capability using a crystal violet staining assay were performed. Using ITS sequencing as the gold standard, the clinical isolates were identified as follows: 44R. mucilaginosaisolates, 2R. glutinisisolates, 2R. minutaisolates, 2R. dairenensisisolates, and 1Rhodosporidium fluvialeisolate. The environmental isolates included 7R. mucilaginosaisolates and 1R. slooffiaeisolate. Using the ID32C system, along with a nitrate assimilation test, only 90.3% of the isolates tested were correctly identified. In the biofilm formation assay,R. mucilaginosaandR. minutaexhibited greater biofilm formation ability compared to the otherRhodotorulaspecies; the clinical isolates ofR. mucilaginosashowed greater biofilm formation compared to the environmental isolates (P= 0.04). Amphotericin B showed goodin vitroactivity (MIC ≤ 1 μg/ml) against planktonic cells, whereas voriconazole and posaconazole showed poor activity (MIC50/MIC90, 2/4 μg/ml). Caspofungin and fluconazole MICs were consistently high for all isolates tested (≥64 μg/ml and ≥ 4 μg/ml, respectively). In this study, we emphasized the importance of molecular methods to correctly identifyRhodotorulaspecies isolates and non-R. mucilaginosaspecies in particular. The antifungal susceptibility profile reinforces amphotericin B as the antifungal drug of choice for the treatment ofRhodotorulainfections. To our knowledge, this is the first study evaluating putative differences in the ability of biofilm formation among differentRhodotorulaspecies.


2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Jessica J. Talbot ◽  
Jens C. Frisvad ◽  
Jacques F. Meis ◽  
Ferry Hagen ◽  
Paul E. Verweij ◽  
...  

ABSTRACT The past decade has seen an increase in aspergillosis in humans and animals due to Aspergillus viridinutans species complex members. Azole resistance is common to these infections, carrying a poor prognosis. cyp51A gene mutations are the main cause of acquired azole resistance in Aspergillus fumigatus. This study aimed to determine if the azole-resistant phenotype in A. viridinutans complex members is associated with cyp51A mutations or extrolite profiles. The cyp51A gene of clinical and environmental isolates was amplified using novel primers, antifungal susceptibility was tested using the Clinical and Laboratory Standards Institute methodology, and extrolite profiling was performed using agar plug extraction. Very high azole MICs were detected in 84% of the isolates (31/37). The MICs of the newer antifungals luliconazole and olorofim (F901318) were low for all isolates. cyp51A sequences revealed 113 nonsynonymous mutations compared to the sequence of wild-type A. fumigatus. M172A/V and D255G, previously associated with A. fumigatus azole resistance, were common among all isolates but were not correlated with azole MICs. Two environmental isolates with nonsusceptibility to itraconazole and high MICs of voriconazole and isavuconazole harbored G138C, previously associated with azole-resistant A. fumigatus. Some novel mutations were identified only among isolates with high azole MICs. However, cyp51A homology modeling did not cause a significant protein structure change for these mutations. There was no correlation between extrolite patterns and susceptibility. For A. viridinutans complex isolates, cyp51A mutations and the extrolites that they produced were not major causes of antifungal resistance. Luliconazole and olorofim show promise for treating azole-resistant infections caused by these cryptic species.


2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Dipika Shaw ◽  
Shreya Singh ◽  
Sunil Dogra ◽  
Jyothi Jayaraman ◽  
Ramesh Bhat ◽  
...  

ABSTRACT Dermatophytosis due to the Trichophyton mentagrophytes-Trichophyton interdigitale complex is being increasingly reported across India. Reports of therapeutic failure have surfaced recently, but there are no clinical break points (CBP) or epidemiological cutoffs (ECVs) available to guide the treatment of dermatophytosis. In this study, a total of 498 isolates of the T. mentagrophytes-interdigitale complex were collected from six medical centers over a period of five years (2014 to 2018). Antifungal susceptibility testing of the isolates was carried out for itraconazole, fluconazole, ketoconazole, voriconazole, luliconazole, sertaconazole, miconazole, clotrimazole, terbinafine, amorolfine, naftifine, ciclopirox olamine, and griseofulvin. The MICs (in mg/liter) comprising >95% of the modeled populations were as follows: 0.06 for miconazole, luliconazole, and amorolfine; 0.25 for voriconazole; 0.5 for itraconazole, ketoconazole, and ciclopirox olamine; 1 for clotrimazole and sertaconazole; 8 for terbinafine; 16 for naftifine; 32 for fluconazole; and 64 for griseofulvin. A high percentage of isolates above the upper limit of the wild-type MIC (UL-WT) were observed for miconazole (29%), luliconazole (13.9%), terbinafine (11.4%), naftifine (5.2%), and voriconazole (4.8%), while they were low for itraconazole (0.2%). Since the MICs of itraconazole were low against the T. mentagrophytes-interdigitale complex, this could be considered the choice of first-line treatment. The F397L mutation in the squalene epoxidase (SE) gene was observed in 77.1% of isolates with a terbinafine MIC of ≥1 mg/liter, but no mutation was detected in isolates with a terbinafine MIC of <1 mg/liter. In the absence of CBPs, evaluation of the UL-WT may be beneficial for managing dermatophytosis and monitoring the emergence of isolates with reduced susceptibility.


1988 ◽  
Vol 69 (3) ◽  
pp. 332-339 ◽  
Author(s):  
Tetsuji Inagawa ◽  
Mitsuo Yamamoto ◽  
Kazuko Kamiya ◽  
Hidenori Ogasawara

✓ A total of 299 patients with aneurysmal subarachnoid hemorrhage (SAH) were classified into three age groups, that is, those aged 59 years or younger (Group 1: 159 patients, 53%), those aged 60 to 69 years (Group 2: 85 patients, 28%), and those aged 70 years or older (Group 3: 55 patients, 18%). A comparison was made of the surgical indications and their overall management outcome in these age groups. The overall outcome at 1 year after SAH of Group 3 was significantly poorer than that of Group 1 (p < 0.01) or Group 2 (p < 0.01), but no significant difference could be demonstrated between Groups 1 and 2. Overall, 104 of the 299 patients died, for a mortality rate of 35%. The mortality rate by age group was 29% for Group 1, 33% for Group 2, and 55% for Group 3. Surgery was performed on 122 patients (77%) in Group 1, 56 (66%) in Group 2, and 25 (45%) in Group 3. The overall operative outcome at 1 year after SAH in Group 3 was significantly poorer than that of Group 1 (p < 0.01), but no significant difference was observed in this regard between Groups 1 and 2. The operative mortality rate of the patients in Groups 1 , 2, and 3 who were preoperatively in Hunt and Hess Grades I and II was 1%, 7%, and 22%, respectively (no significant difference). By life-table analysis the 5-year survival probability was 65% for Group 1, 60% for Group 2, and 37% for Group 3. The rate of patients surviving in good condition or in a disabled but independent condition at 1 year after SAH was 93% and no statistically significant difference in survival probability was observed among the three age groups.


1976 ◽  
Vol 45 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Bryce Weir ◽  
Pierre Band ◽  
Raul Urtasun ◽  
Gilles Blain ◽  
Don McLean ◽  
...  

✓ Forty-one consecutive patients with supratentorial primary brain tumors (38 Grade III and IV astrocytomas, one giant-cell astrocytoma, and two cases with insufficient tissue for diagnosis) were randomly allocated within 2 weeks of surgery to one of three therapeutic groups. Group 1 (15 patients) received radiation therapy totaling 4000 to 4500 rads in 4 to 5 weeks. Group 2 (13 patients) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) 130 mg/sq m orally every 6 weeks. Group 3 (13 patients) received radiation therapy plus CCNU as for Groups 1 and 2. When the disease progressed, patients in Groups 1 and 2 were crossed over to receive CCNU and irradiation respectively. The median survival time in these groups was 188, 259, and 252 days, and the mean survival 263, 262, and 329 days. The median time from diagnosis to crossover (Groups 1 and 2) or to progression (Group 3) was 163, 99, and 220 days, and the mean time was 172, 108, and 231 days. There was no statistically significant difference between the means or medians in any of these situations.


2018 ◽  
Vol 62 (4) ◽  
pp. e01927-17 ◽  
Author(s):  
Pavlina Lyskova ◽  
Vit Hubka ◽  
Lucie Svobodova ◽  
Vanessa Barrs ◽  
Navneet K. Dhand ◽  
...  

ABSTRACT Cryptic species of Aspergillus fumigatus, including the Aspergillus viridinutans species complex, are increasingly reported to be causes of invasive aspergillosis. Their identification is clinically relevant, as these species frequently have intrinsic resistance to common antifungals. We evaluated the susceptibilities of 90 environmental and clinical isolates from the A. viridinutans species complex, identified by DNA sequencing of the calmodulin gene, to seven antifungals (voriconazole, posaconazole, itraconazole, amphotericin B, anidulafungin, micafungin, and caspofungin) using the reference European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. The majority of species demonstrated elevated MICs of voriconazole (geometric mean [GM] MIC, 4.46 mg/liter) and itraconazole (GM MIC, 9.85 mg/liter) and had variable susceptibility to amphotericin B (GM MIC, 2.5 mg/liter). Overall, the MICs of posaconazole and the minimum effective concentrations of echinocandins were low. The results obtained by the EUCAST method were compared with the results obtained with Sensititre YeastOne (YO) panels. Overall, there was 67% agreement (95% confidence interval [CI], 62 to 72%) between the results obtained by the EUCAST method and those obtained with YO panels when the results were read at 48 h and 82% agreement (95% CI, 78 to 86%) when the results were read at 72 h. There was a significant difference in agreement between antifungals; agreement was high for amphotericin B, voriconazole, and posaconazole (70 to 86% at 48 h and 88 to 93% at 72 h) but was very low for itraconazole (37% at 48 h and 57% at 72 h). The agreement was also variable between species, with the maximum agreement being observed for A. felis isolates (85 and 93% at 48 and 72 h, respectively). Elevated MICs of voriconazole and itraconazole were cross-correlated, but there was no correlation between the other azoles tested.


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