Acute calculous cholecystitis is one of the most frequent causes of emergency abdominal surgery worldwide and represents a major complication of gallstone disease. Contemporary guidelines increasingly support early surgical management, with laparoscopic cholecystectomy (LC) adopted broadly as the preferred approach when feasible [1-3]. Meta-analytic data and recent systematic reviews report that LC is associated with shorter hospital stay, reduced postoperative wound infection and overall lower morbidity compared with open cholecystectomy (OC), while maintaining comparable rates of major biliary complications in appropriately selected patients [1,4].

Despite these advantages, LC in the acute setting carries a recognized risk of conversion to an open procedure and of procedure-related complications when dense inflammation, gangrene or pericholecystic abscesses are present. Several cohort studies have identified predictors of conversion and adverse outcomes — notably advanced age, markedly elevated inflammatory markers (e.g., C-reactive protein), diabetes and gangrenous change — which must be considered when planning the operative strategy [4-6]. Early randomized data and subsequent trials have suggested that, for many patients with acute or gangrenous cholecystitis, LC can be performed safely with outcomes similar or superior to open surgery when experienced laparoscopic surgeons and appropriate intraoperative safety strategies are employed [5].

Guideline updates (including the Tokyo Guidelines 2018 and the WSES 2020 recommendations) therefore recommend that LC be considered the first-line operative option for most patients with acute calculous cholecystitis, reserving OC or bailout strategies (conversion, subtotal cholecystectomy) for cases in which anatomy is hostile or patient factors preclude safe laparoscopic dissection [2,3]. Nonetheless, heterogeneity in patient presentation, surgical experience and institutional resources means that direct, contemporary comparisons of perioperative parameters and patient-centered outcomes between LC and OC remain important to inform local practice. Accordingly, this study was undertaken to compare intraoperative metrics, postoperative morbidity and recovery parameters between laparoscopic and open cholecystectomy in patients presenting with acute calculous cholecystitis.

This was a prospective, comparative, observational study conducted at an hospital. The study was designed to evaluate the clinical outcomes, perioperative parameters, and complications associated with laparoscopic versus open cholecystectomy in patients presenting with acute calculous cholecystitis. Sample Size and Study Population: Based on previous studies and an expected difference in postoperative complication rates between laparoscopic and open cholecystectomy of approximately 20%, with a power of 80% and α = 0.05, the minimum required sample size was calculated to be 60 patients per group. To account for possible dropouts, a total of 140 patients were enrolled and equally allocated to either the laparoscopic cholecystectomy group (n=70) or the open cholecystectomy group (n=70). Inclusion Criteria: Patients fulfilling all of the following criteria were included in the study: • Age 18–70 years. • Clinical diagnosis of acute calculous cholecystitis based on the Tokyo Guidelines 2018, including right upper quadrant pain, tenderness, and supportive laboratory/imaging findings. • Fit for general anesthesia as per ASA Physical Status I–III. Exclusion Criteria: Patients with any of the following were excluded: • Gallbladder perforation or generalized peritonitis. • Previous upper abdominal surgery precluding laparoscopic access. • Coagulopathy or immunosuppression. • Pregnancy. Preoperative Assessment: All patients underwent detailed clinical examination, routine hematological investigations (complete blood count, liver function tests, coagulation profile), and imaging with abdominal ultrasonography. In selected cases, contrast-enhanced CT of the abdomen was performed for complicated presentations. Surgical Procedure • Laparoscopic Cholecystectomy (LC): Standard four-port technique under general anesthesia. Pneumoperitoneum was established with CO₂ to 12–14 mmHg. The cystic duct and artery were identified, clipped, and divided. Gallbladder was dissected from the liver bed using electrocautery and retrieved through the umbilical port. • Open Cholecystectomy (OC): Right subcostal (Kocher) incision was used. The gallbladder was dissected from the liver bed, and cystic structures were ligated. Hemostasis was ensured, and the incision closed in layers with a drain left as indicated. Postoperative Care: All patients received standard postoperative analgesia and antibiotic prophylaxis. Early mobilization and oral intake were encouraged as tolerated. Postoperative complications such as wound infection, bile leak, bleeding, and pulmonary complications were recorded. Length of hospital stay and time to return to normal activity were noted. Outcome Measures: Primary outcomes included operative time, intraoperative blood loss, postoperative complications, and length of hospital stay. Secondary outcomes included time to return to normal activity and patient satisfaction. Statistical Analysis: Data were entered into Microsoft Excel and analyzed using SPSS version 25. Continuous variables were expressed as mean ± standard deviation and compared using the Student’s t-test. Categorical variables were expressed as frequencies and percentages and analyzed using the Chi-square test. A p-value <0.05 was considered statistically significant.

Demographic and Clinical Patterns

A total of 210 culture-confirmed dermatophytosis cases were enrolled. Table 1 presents demographic and clinical characteristics stratified by infection type. The mean age was 34.8 ± 14.2 years and males predominated overall (62.9%). Tinea corporis was the most common presentation (32.4%), followed by tinea cruris (24.8%), tinea unguium (21.9%), and tinea capitis (13.3%). Topical corticosteroid misuse was documented in 40.0% of cases overall, with the highest prevalence in tinea corporis (52.9%) and tinea cruris (46.2%). Recurrent disease was reported by 43.8% of patients, and 61.0% reported prior antifungal use. Diabetes mellitus was most prevalent among tinea unguium patients (34.8%), and tinea capitis occurred exclusively in children aged under 14 years.

Table 1. Demographic and Clinical Characteristics by Infection Type (n=210)

Values are n (%) unless otherwise stated. SD = Standard Deviation. Mixed/Other includes tinea pedis, tinea manuum, and mixed-site infections.

Species Distribution

Table 2 summarizes the distribution of dermatophyte species across infection types. T. mentagrophytes complex was the predominant organism overall (39.0%), with the highest prevalence in tinea cruris (50.0%). T. rubrum accounted for 32.4% of isolates and was the dominant species in tinea unguium (52.2%). T. violaceum and M. canis were primarily associated with tinea capitis (35.7% and 28.6% of capitis cases, respectively). ITS sequencing confirmed that 74.4% of T. mentagrophytes complex isolates belonged to the Indian epidemic genotype (ITS type VIII), associated with high terbinafine resistance rates.

Table 2. Dermatophyte Species Distribution by Infection Type (n=210)

Values are n (%). Species totals may not sum to column totals due to mixed-site infections. ITS sequencing performed for T. mentagrophytes complex isolates (n=82).

Antifungal Susceptibility Profiles

MIC distributions for major antifungal agents against the principal species are presented in Table 3. Terbinafine resistance was observed in 31.7% of T. mentagrophytes and 16.2% of T. rubrum isolates. Fluconazole demonstrated the poorest in vitro activity, with resistance rates of 43.9% and 36.8% against T. mentagrophytes and T. rubrum respectively; given its limited use as a primary antifungal for dermatophytosis, this likely reflects intrinsic reduced susceptibility rather than acquired resistance. Voriconazole demonstrated superior activity compared to fluconazole, with resistance rates of 17.1% and 11.8% for the two major species. Itraconazole resistance was detected in 19.5% of T. mentagrophytes and 13.2% of T. rubrum. Griseofulvin showed resistance rates of 29.3% and 17.6% for T. mentagrophytes and T. rubrum respectively.

Table 3. Minimum Inhibitory Concentration (MIC) Profiles by Antifungal Agent and Species

MIC50/MIC90 = MIC values inhibiting 50%/90% of isolates. Resistance breakpoints based on EUCAST epidemiological cut-off values (ECOFFs): Terbinafine >0.5 µg/mL; Itraconazole >1 µg/mL; Fluconazole >8 µg/mL; Voriconazole >1 µg/mL; Griseofulvin >1 µg/mL. Intermediate category represents values above ECOFF but below MIC90 for clearly resistant strains.

SQLE Mutations in Terbinafine-Resistant Isolates

Sequencing of the SQLE hot-spot region was performed on 46 isolates with terbinafine MIC ≥0.5 µg/mL. SQLE mutations were identified in 39 of these (84.8%). Table 4 presents selected representative isolates with their mutation profiles. The F397L substitution was the most frequently encountered mutation (detected in 58.7% of mutant isolates), followed by L393F (28.3%), H440Y (10.9%), and A448T (8.7%). Compound heterozygous mutations (F397L+L393F; F397L+A448T) were associated with the highest MIC values (8–32 µg/mL). Prior terbinafine exposure exceeding 3 months was documented in all high-level (MIC ≥16 µg/mL) resistant isolates. Seven isolates exhibited high-level terbinafine resistance (MIC ≥8) without detectable SQLE mutations, suggesting additional resistance mechanisms (possibly involving drug efflux or altered membrane composition) not captured by coding sequence analysis.

Table 4. SQLE Mutation Profile in Selected Terbinafine-Resistant Isolates

SQLE = Squalene Epoxidase gene. F397L, L393F, H440Y, A448T: single-letter amino acid code; position numbers refer to T. mentagrophytes CBS 371.66 reference sequence. MIC values in µg/mL. Prior terbinafine exposure classified by cumulative duration.

Treatment Outcomes

Table 5 summarizes treatment outcomes by regimen. Overall clinical cure rates at 4 weeks ranged from 69.2% to 88.9%. Combination oral and topical therapy and oral voriconazole achieved the highest cure rates (83.3% and 88.9% respectively) but voriconazole was associated with a substantially higher adverse event rate (33.3%), predominantly transaminase elevation requiring monitoring. Terbinafine monotherapy showed the lowest clinical cure rate (72.2%) in this cohort, consistent with the high prevalence of terbinafine-resistant isolates. Recurrence rates at 3 months were highest in the topical terbinafine group (44.4%) and lowest in the combination therapy group (18.2%), underscoring the importance of adequate treatment duration and systemic therapy for extensive or recalcitrant disease.

Table 5. Treatment Outcomes by Antifungal Regimen

Clinical cure = complete resolution of erythema, scaling, and pruritus at 4 weeks. Mycological cure = negative KOH and culture at 4 weeks. Recurrence = reappearance of clinical features within 3 months of treatment completion. Adverse events principally include gastrointestinal symptoms and transaminase elevation. Regimen allocation was not randomized.

Risk Factors for Antifungal Resistance

Multivariate logistic regression results are presented in Table 6. Prior terbinafine use exceeding 3 months was the strongest independent predictor of resistance (adjusted OR 4.24, 95% CI 2.18–8.23, p<0.001), followed by topical corticosteroid misuse (OR 3.12), tinea incognito presentation (OR 2.86), and recurrent disease of two or more episodes per year (OR 2.47). T. mentagrophytes infection was associated with significantly higher resistance odds compared to T. rubrum (OR 1.98, p=0.023). Diabetes mellitus and immunocompromised status showed elevated point estimates but did not reach statistical significance after adjustment. Sex and urbanicity were not independent predictors.

Table 6. Multivariate Logistic Regression: Independent Predictors of Terbinafine Resistance

OR = Odds Ratio; CI = Confidence Interval. *Statistically significant (p<0.05). Nagelkerke R² = 0.44; Hosmer-Lemeshow goodness-of-fit p=0.68. Reference categories: T. rubrum (for species); female (for sex); rural (for residence). Adjusted ORs from backward stepwise regression (entry p<0.05, removal p>0.10).

This prospective clinico-mycological study provides comprehensive data on the epidemiology, species distribution, antifungal susceptibility, resistance mechanisms, and treatment outcomes of dermatophytosis in a tertiary care center in Telangana, India. Our findings document an alarming prevalence of terbinafine resistance—31.7% among T. mentagrophytes complex isolates and 16.2% among T. rubrum—driven predominantly by SQLE point mutations and strongly associated with identifiable, modifiable clinical exposures.

The predominance of T. mentagrophytes complex (39.0%) over T. rubrum (32.4%) in our cohort is a notable shift from historical Indian data, which consistently identified T. rubrum as the leading isolate across most tinea types. This epidemiological transition has been documented progressively since approximately 2013–2014 across multiple Indian centers, and is attributed to the emergence and clonal expansion of the terbinafine-resistant Indian epidemic genotype. The near-exclusive association of T. violaceum and M. canis with tinea capitis in our cohort is consistent with global literature and reflects the distinct ecologic niches and transmission routes of zoophilic and anthropophilic dermatophytes.

Our terbinafine resistance rates are concordant with, and in some analyses exceed, those reported by recent Indian multicenter studies. Singh et al. (2014) documented terbinafine resistance in 24.6% of T. mentagrophytes complex isolates in New Delhi, while Gupta et al. (2014) reported 28.3% resistance in a pan-India survey. The somewhat higher rate in our cohort (31.7%) may reflect regional prescribing practices, a high proportion of referred refractory cases, or the specific patient demographics of a tertiary institution. The F397L mutation, identified in 58.7% of sequenced resistant isolates, has consistently been the dominant SQLE alteration in Indian epidemic isolates, and our data corroborate this finding. The presence of compound mutations (F397L+L393F; F397L+A448T) in the most resistant isolates (MIC ≥16 µg/mL) suggests stepwise mutational accumulation driven by continued drug pressure under inadequate therapy.

Topical corticosteroid misuse emerged as the second-strongest predictor of resistance (OR 3.12) and was documented in 40.0% of our entire cohort—a figure that likely underestimates true prevalence given recall bias and the widespread availability of steroid-antifungal combinations without prescription. The pathomechanism by which corticosteroid use promotes resistance is multifactorial: local immunosuppression reduces the host inflammatory response that partially constrains fungal replication, thereby increasing fungal burden and the probability of spontaneous resistance mutations; simultaneously, the concurrent antifungal component in compound preparations provides intermittent, subtherapeutic drug exposure that selects for resistant mutants without achieving mycological cure. The resulting tinea incognito phenotype—the modified, non-pruritic, less erythematous presentation—delays diagnosis and prolongs the selection window. Regulatory restriction of over-the-counter sales of potent corticosteroid-antifungal combinations is an urgent public health priority.

Voriconazole demonstrated the most favorable in vitro activity against terbinafine-resistant isolates in our study, consistent with its broad-spectrum triazole mechanism of action and the preservation of azole susceptibility in SQLE-mutant strains (which affect the allylamine but not the azole target). However, the high rate of adverse events observed (33.3%, primarily transaminase elevation) with oral voriconazole cautions against its routine use as first-line therapy and argues for reservation as salvage treatment for documented resistant, refractory cases. Itraconazole, with a resistance rate of 19.5% in T. mentagrophytes and a more manageable safety profile, appears to be a reasonable first alternative to terbinafine pending susceptibility results in patients with recurrent or atypical disease, particularly at pulse dosing schedules.

The recurrence rate of 34.6% at 3 months in the terbinafine monotherapy group, compared to 18.2% in the combination therapy group, highlights the inadequacy of current standard-of-care treatment durations and the clinical significance of in vitro resistance. These findings underscore the need for susceptibility-guided prescribing rather than reflexive empirical terbinafine therapy, especially in patients with identified risk factors for resistance. Several limitations warrant acknowledgment: as a single-center tertiary referral study, our case mix may over-represent severe and refractory disease; the unrandomized treatment allocation precludes efficacy comparisons between regimens; and long-term follow-up data beyond 3 months are not available. Additionally, while SQLE coding sequence mutations account for most resistance, alternative mechanisms (efflux pumps, promoter region variants, non-coding SQLE changes) were not fully interrogated and may account for the sequencing-negative resistant isolates.

particularly high-level terbinafine resistance mediated by SQLE mutations in the Indian epidemic T. mentagrophytes genotype—is a clinically significant and prevalent phenomenon in Telangana, India. The strong and independent associations with prior terbinafine exposure, topical corticosteroid misuse, and recurrent disease point to clear, actionable targets for intervention. We recommend: (1) inclusion of antifungal susceptibility testing in the workup of recurrent, extensive, or treatment-refractory tinea; (2) urgent regulatory restriction of over-the-counter potent topical corticosteroid-antifungal combinations; (3) prescriber education on rational antifungal use, adequate treatment duration, and the avoidance of subtherapeutic courses; and (4) establishment of a national sentinel surveillance system for dermatophyte antifungal resistance with standardized reporting. Voriconazole and combination therapy offer viable options for documented resistant cases but require careful monitoring. Future randomized controlled trials comparing treatment strategies in terbinafine-resistant dermatophytosis are urgently needed.

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