An Observational Study of Fungal Infections in COVID-19: Highlighting the Role of Mucormycosis in Tertiary Healthcare Settings.

Background Fungal infections, especially mucormycosis, have remarkably surged during the coronavirus disease 2019 (COVID-19) era, especially during the second wave peak of the pandemic raising the concern of the clinicians for the admitted patients. Steroid therapy, diabetes, and other immunocompromised states are more commonly associated with COVID-19-associated mucormycosis (CAM). Aim and objective The aim of this study is to ascertain the prevalence of fungal infections amidst the second wave of the COVID-19 pandemic and discern the associated risk factors. Materials and methods During the second peak of COVID-19, samples were received in the microbiology laboratory from all clinically suspected mucormycosis patients. These samples underwent processing for potassium hydroxide (KOH) wet mount, fungal culture on Sabouraud's dextrose agar (SDA) medium, and COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) testing. All relevant clinical and associated risk factors were tabulated and analyzed. Results Among the 107 suspected cases of mucormycosis, 39 (36.4%) were confirmed positive for COVID-19 via RT-PCR, while 68 (63.6%) tested negative. Males exhibited a predominant infection rate, with the rhinocerebral system being the most commonly affected site. Significantly higher mortality rates were observed in COVID-19-associated mucormycosis (CAM) patients (33.4%) compared to those without COVID-19 (5.9%), with a notable p-value of 0.0005. CAM patients also demonstrated a higher frequency of ICU admissions (77%) compared to non-COVID-19-associated mucormycosis patients (21.4%), a statistically significant finding (p-value of 0.007). Additionally, immunocompromised states, diabetes, and the administration of oxygen therapy were identified as significant risk factors in CAM (p < 0.05). Notably, mucormycosis accounted for the majority of fungal isolates (48.27%) among COVID-19 patients. Conclusion Mucormycosis infection is more commonly seen in COVID-19-infected patients as compared to non-COVID-19 patients, especially with comorbidities such as diabetes mellitus, steroid usage, and other immunocompromised states.

Comparative performance of biofire pneumonia panel and standard culture-based methods for diagnosing pneumonia in critically ill patients: Impact on antibiotic stewardship.

INTRODUCTION: Lower respiratory tract infections (LRTIs) are a common cause of morbidity and mortality worldwide. Accurate identification of the pathogens causing LRTIs is crucial for ensuring of diagnostic and antibiotic stewardship. The Biofire Pneumonia Panel (BFPP) is a molecular diagnostic test that allows rapid detection of various bacterial and viral pathogens. In this study, we compared the performance of BFPP with standard culture methods for the detection of pathogens. MATERIALS AND METHODS: Respiratory samples from 70 patient with suspected LRTIs were tested using both BFPP and standard culture methods. The distribution of isolated bacterial pathogens was analyzed, and the sensitivity and specificity of BFPP were calculated. Additionally, the performance of BFPP in detecting antimicrobial resistance genes was evaluated. The results were compared with those obtained from VITEK-2 antimicrobial susceptibility testing and culture-based methods. RESULTS: Among the suspected LRTI cases, BFPP identified a single pathogen in 32.8% of cases and multiple pathogens in 40% of cases. The standard culture method detected a single pathogen in 47.1% of cases. BFPP showed a sensitivity of 93.9% and a specificity of 45.9% for the total sample. The performance of BFPP in detecting antimicrobial resistance genes varied for different pathogens with overall sensitivity of 40.1% and specificity of 95.9%. CONCLUSION: The Biofire Pneumonia Panel (BFPP) demonstrated high sensitivity for several bacterial pathogens, indicating its potential as a rapid diagnostic tool. However, its performance varied for different microorganisms, and it had limitations in detecting certain pathogens and antimicrobial resistance genes for which still required more further studies to explore different resistance gene mechanism that can be incorporated in this panel in future. The BFPP can complement standard culture methods as a rapid tool in the diagnosis of LRTIs.

Revolutionizing Tuberculosis Treatment: Uncovering New Drugs and Breakthrough Inhibitors to Combat Drug-Resistant Mycobacterium tuberculosis.

Tuberculosis (TB) is a global health threat that causes significant mortality. This review explores chemotherapeutics that target essential processes in Mycobacterium tuberculosis, such as DNA replication, protein synthesis, cell wall formation, energy metabolism, and proteolysis. We emphasize the need for new drugs to treat drug-resistant strains and shorten the treatment duration. Emerging targets and promising inhibitors were identified by examining the intricate biology of TB. This review provides an overview of recent developments in the search for anti-TB drugs with a focus on newly validated targets and inhibitors. We aimed to contribute to efforts to combat TB and improve therapeutic outcomes.

Post mastectomy pain syndrome at an Indian tertiary cancer centre and its impact on quality of life.

Background: Literature on Post mastectomy pain in the Indian population is scarce. Most literature is from the West. The current study aimed to identify the incidence of post-mastectomy pain syndrome (PMPS), pain severity, and its impact on quality of life in Indian patients. Method: Prospective observational study of 120 women undergoing mastectomy between March and December 2017, followed until 6 months after surgery. The Brief Pain Inventory (BPI) questionnaire and the quality of life questionnaire (QLQ) by the European Organization for Research and Treatment of Cancer (EORTC) and known as (EORTC-QLQ 30) were used to identify the impact on function and quality of life. Results: A 35.8% PMPS incidence was identified at 6 months after mastectomy. Pain was located in the anterior chest wall (41.8%), axilla (32.6%), and medial upper arm (25.6%). Most (48.8%) patients described it as dull aching and of mild intensity (55.8%). No significant association of age, BMI, surgery, Intercostobrachial nerve (ICBN) dissection, postoperative pain severity, pain history {dysmenorrhea, headache}, and postoperative radiotherapy with PMPS was found. Pain interfered with daily activities and quality of life in those with PMPS, as deduced from BPI and EORTC-QLQ. Conclusion: PMPS is very much a problem affecting the quality of life in our set of patients. Most women tried to cope and accept the pain as part of the treatment process. This shows the need for creating awareness about PMPS among healthcare providers and patients alike. Early identification and treatment of post mastectomy pain should be an essential aspect of patient care.

Severe Sepsis Due to Chryseobacterium indologenes, a Possible Emergent Multidrug-Resistant Organism in Intensive Care Unit-Acquired Infections.

Opportunistic infections in the intensive care unit are quite common which can cause devastating disease in many hospitalized and immunocompromised patients. Chryseobacterium indologenes is one such microorganism which is an emerging cause of nosocomial infections. Many cases had been reported from its infections, but the treatment protocol for its management is still not established. We present two cases of C. indologenes infections which were hospital acquired. The pandrug-resistant nature of the bacteria and the associated mortality were uncommon with these two cases.

Emergence of Carbapenem Resistant Non-Fermenting Gram-Negative Bacilli Isolated in an ICU of a Tertiary Care Hospital.

INTRODUCTION: The emergence and spread of Multi-Drug Resistant (MDR) Non-Fermenting Gram-Negative Bacilli (NFGNB) in Intensive Care Units (ICU) and their genetic potential to transmit diverse antibiotic resistance regardless of their ability to ferment glucose poses a major threat in hospitals. The complex interplay of clonal spread, persistence, transmission of resistance elements and cell-cell interaction leads to the difficulty in controlling infections caused by these multi drug-resistant strains. Among non-fermenting Gram-negative rods, the most clinically significant species Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia are increasingly acquiring resistant to carbapenems. Carbapenems once considered as a backbone of treatment of life threatening infections appears to be broken as the resistance to carbapenems is on rise. AIM: To document the prevalence of carbapenem resistance in non-fermenting Gram-negative bacilli isolated from patients with respiratory tract infections in the ICU of Himalayan Institute of Medical Sciences, Dehradun. MATERIALS AND METHODS: This is a cross-sectional study conducted in ICU patients between October 2015 to March 2016. A total of 366 lower respiratory tract samples were collected from 356 patients with clinical evidence of lower respiratory tract infections in form of Endotracheal (ET) aspirate, Tracheal Tube (TT) aspirate and Bronchoalveolar Lavage (BAL) specimen. Organism identification and the susceptibility testing was done by using an automated system VITEK 2. RESULTS: Out of 366 samples received 99 NFGNB were isolated and most common sample was ET aspirate sample 256 (64.5%). Acinetobacter baumannii was the most common NFGNB isolated 63 (63.63%) followed by Pseudomonas aeruginosa 25 (25.25%), Elizabethkingia meningoseptica seven (7.07%) and Strenotrophomonas maltophilia four (4.04%). We observed that 90.5% Acinetobacter baumannii were resistant to imipenem and 95.2% resistant to meropenem, Pseudomonas aeruginosa came out to be 52% resistant to imipenem and 56% resistant to meropenem while Stenotrophomonas maltophilia and Elizabethkingia meningoseptica were 100% resistant to carbapenems as they are intrinsically resistant to carbapenems. CONCLUSION: The resistance rate of carbapenems for NFGNB infections is very high in our study and variable in different regions. Overall carbapenem resistance is on rise. So, the infection control team and microbiologist needs to work together to determine the risk carried by multi drug resistant non-fermenting gram-negative infections and the resistance surveillance programs are mandatory to control these bacteria in ICU settings.

Diagnostic performance of automated liquid culture and molecular line probe assay in smear-negative pulmonary tuberculosis.

The diagnosis of smear-negative pulmonary tuberculosis (PTB) is particularly challenging, and automated liquid culture and molecular line probe assays (LPA) may prove particularly useful. The objective of our study was to evaluate the diagnostic potential of automated liquid culture (ALC) technology and commercial LPA in sputum smear-negative PTB suspects. Spot sputum samples were collected from 145 chest-symptomatic smear-negative patients and subjected to ALC, direct drug susceptibility test (DST) testing and LPA, as per manufacturers' instructions. A diagnostic yield of 26.2% was observed among sputum smear-negative TB suspects with 47.4% of the culture isolates being either INH- and/or rifampicin-resistant. Complete agreement was observed between the results of ALC assay and LPA except for two isolates which demonstrated sensitivity to INH and rifampicin at direct DST but were rifampicin-resistant in LPA. Two novel mutations were also detected among the multidrug isolates by LPA. In view of the diagnostic challenges associated with the diagnosis of TB in sputum smear-negative patients, our study demonstrates the applicability of ALC and LPA in establishing diagnostic evidence of TB.

ESBL and MBL in Cefepime Resistant Pseudomonas aeruginosa: An Update from a Rural Area in Northern India.

INTRODUCTION: Cefepime, a fourth generation cephalosporin, is widely used for the empirical treatment of serious infections in critically ill hospitalized patients. Pseudomonas aeruginosa (P. aeruginosa), one of the commonest bacteria causing nosocomial infections has a propensity to develop antibiotic resistance quite promptly. AIM: We undertook this study to assess the efficacy of cefepime against current clinical isolates of P. aeruginosa and to study existence of different beta-lactamase enzymes among cefepime resistant P. aeruginosa isolates. MATERIALS AND METHODS: Total of 618 isolates of P. aeruginosa recovered consecutively from various clinical samples of a tertiary care hospital were analysed. Their Antimicrobial sensitivity profile against piperacilin (100µg), piperacillin/tazobactam (100µg/10µg), ceftazidime (30µg), cefoperazone (75µg), cefepime (30µg), ciprofloxacin (5µg), gentamycin (10µg), amikacin (30µg) and imipenem (10µg) (Himedia) was tested by Kirby-Bauer disc diffusion method (Clinical and Laboratory Standards Institute guidelines). We further looked for ESBL, MBL and ESBL + MBL co producers among the cefepime resistant isolates by two different methods (combined double disc synergy test, imipenem-EDTA combined disc test and vitek2). RESULTS: Among 618 consecutive clinical isolates of P. aeruginosa, we observed resistance to cefepime in 457 (74%) isolates. We observed resistance to ciprofloxacin (n=506, 82%) in maximum number of isolates followed by that to Gentamycin (n=475, 77%), amikacin (n=366, 60%), and cefoperazone (n=350, 56.6%). Among all our cefepime resistant P. aeruginosa isolates only 27(6%) were ESBL producers, 18(4%) MBL producers and 2(0.4%) were ESBL+ MBL co-producers. All the ESBL and MBL isolates were also tested by VITEK 2 advanced expert system (bioMirieux Vitek Systems Inc, Hazelwood, MO, France) which revealed a 100% concordance with the phenotypic method tested. CONCLUSION: This paper highlights the need to reconsider prescribing empirical antibiotics for Pseudomonas infections in this region and formulate a strong antibiotic policy to curb the menace of spread of multidrug resistant strains.

Granzyme B as a diagnostic marker of tuberculosis in patients with and without HIV coinfection.

Immunodiagnostic tests for tuberculosis (TB) are based on the estimation of interferon γ (IFN-γ) or IFN-γ-secreting CD4(+) T cells following ex vivo stimulation with ESAT6 and CFP-10. Sensitivity of these tests is likely to be compromised in CD4(+) T-cell-depleted situations, like HIV-TB coinfection. CD4(+) and CD8(+) T cells, isolated from 3 groups, viz., HIV-negative patients with active TB, HIV-TB coinfected patients, and healthy household contacts (HHCs) were cocultivated with autologous dendritic cells, and the cytokine response to rESAT6 stimulation was compared between groups in supernatants. While CD4(+) T-cell stimulation yielded significantly elevated levels of IFN-γ and interleukin 4 in HIV-negative TB patients, compared to HHCs, the levels of both these cytokines were nondiscriminatory between HIV-positive TB patients and HHCs. However, CD8(+) T-cell stimulation yielded significantly elevated granzyme B titers in both groups of patients, irrespective of HIV coinfection status. Hence, contrary to IFN-γ, granzyme B might be a useful diagnostic marker for Mycobacterium tuberculosis infection particularly in HIV coinfected patients.

Amphotericin B Resistant Apophysomyces elegans Causing Rhino-oculo-Cerebral Mucormycosis in an Immunocompetent Host.

Mucormycosis, an angioinvasive infection is caused by the ubiquitous filamentous fungi of the order Mucorales and class Mucormycetes. Reports of this disease are on the rise over the past few decades. Rhino-oculo-Cerebral presentation associated with uncontrolled diabetes is the predominant characteristic of this entity. We report here a case of rhinooculocerebral mucormycosis (ROCM) due to Apophysomyces elegans (A. elegans) in a 45-year-old diabetic lady with background illness of hypothyroidism and polyradiculoneuropathy. Though this condition is usually managed with surgical debridement of the affected tissue and medical therapy with Amphotericin B, the isolate recovered in our case was found to be resistant to Amphotericin B.

Epidemiological and mycological characteristics of candidemia in patients with hematological malignancies attending a tertiary-care center in India.

BACKGROUND AND OBJECTIVES: We undertook the present study to ascertain the contributing risk factors and explore the epidemiological and mycological characteristics of opportunistic candidemia among patients with hematological malignancies. DESIGN AND SETTINGS: Observational cross-sectional study in a tertiary care center. PATIENTS AND METHODS: Consecutive patients with hematological malignancies reporting to the collaborating medical and pediatric units with a febrile episode were recruited and screened for candidemia by blood culture. Recovered Candida isolates were speciated and antifungal susceptibility testing was performed as per Clinical and Laboratory Standards Institute guideline (CLSI) guidelines M44-A. Further analysis was done for potential risk factors and compared between culture positive and negative patients. RESULTS: Of 150 patients recruited, the majority (n=27) were between 51 and 60 years and the male to female ratio was 1.63:1. Fifteen patients (10%) were culture positive. The culture positivity was significantly higher in acute lymphocytic leukemia (ALL) than in non-ALL patients (p=0.03). There was significant association of candidaemia with leucopenia, chemotherapeutic drugs, corticosteroids and presence of indwelling devices. Duration of disease (p=0.032) and duration of hospitalization (p=0.003) were significantly prolonged in culture positive patients. C. tropicalis was the commonest isolate (46.67%), with non- Candida albicans outnumbering C. albicans in all categories of hematological malignancies (2.75:1). All isolates of C. albicans were uniformly sensitive to all the azoles, but only 50% were sensitive to amphotericin B and none to nystatin and flucytosine. CONCLUSIONS: This observational study identifies ALL and chronic lymphocytic leukemia (CLL) as the forms of hematological malignancy predominantly associated with candidemia; specifies risk factors and chemotherapeutic agents predisposing patients towards its occurrence; reports a preponderance of C. tropicalis among the causative agents and finds voriconazole to be the most effective antifungal agent against the recovered isolates. This information could assist in tailoring prophylactic and therapeutic antifungal practices for this infection, according to local epidemiological and mycological characteristics.

Non traumatic keratitis due to colletotrichum coccodes: a case report.

Colletotrichum species, a rare and emerging fungus is a well- known plant pathogen and an uncommon cause of human infection. It has been implicated as the etiological agent of cutaneous phaeohyphomycosis and keratitis, particularly following colonization of traumatized tissues or in immunocompromised patients. However, it has hardly ever been reported in the absence of such predisposing risk factors. Here, we report a case of keratitis with Colletotrichum coccodes occurring in a middle- aged, immunocompetent person without any history of trauma or co-morbidity. The isolate was sensitive to Amphotericin B and Voriconazole, and accordingly the patient was treated successfully with ocular administration of Amphotericin B.

Ibuprofen-mediated reversal of fluconazole resistance in clinical isolates of Candida.

INTRODUCTION: In view of the increasing prevalence of invasive Candidiasis in today's health-care scenario and the emergence of fluconazole resistance among clinical isolates of Candida, we sought to determine if Ibuprofen could elicit a reversal of fluconazole resistance and thereby offer a potential therapeutic breakthrough in fluconazole-resistant Candidiasis. MATERIALS AND METHODS: We selected 69 clinical isolates of Candida, which demonstrated an MIC of >32 µg/ml for fluconazole, and subjected them to broth microdilution in presence and absence of Ibuprofen. RESULTS: Forty two of the 69 isolates (60.9%) demonstrated reversal of Fluconazole resistance with concomitant use of Ibuprofen. This was characterized by significant species-wise variation (p=0.00008), with all the C. albicans isolates and none of the C. glabrata isolates demonstrating such reversal. Only 22.2% and 37.7% of C. krusei and C. tropicalis isolates respectively showed Ibuprofen-mediated reversal of Fluconazole resistance. CONCLUSION: Since Ibuprofen is a known efflux pump inhibitor, our findings hint at the possible mechanism of Fluconazole resistance in most of our Candida isolates and suggest a potential therapeutic alternative that could be useful in the majority of Fluconazole-resistant clinical isolates of Candida.

Fluconazole Resistant Candida Oesophagitis in Immunocompetent Patients: Is Empirical Therapy Justifiable?

INTRODUCTION: C. albicans (Candida albicans) is the foremost cause of fungal oesophagitis, however other species such as Candida tropicalis, Candida krusei and Candida stellatoidea have also been implicated to cause this condition. Although, numerous studies have identified risk factors for C. albicans oesophagitis, data for non- C. albicans species is still sparse. AIM: To determine the aetiology of Candida oesophagitis in our medical centre over a two year period. Additionally, to investigate predisposing conditions for oesophageal candidiasis caused by different Candida species. MATERIAL AND METHODS: All consecutive patients posted for upper gastrointestinal endoscopy at the endoscopy unit of a tertiary care hospital in north India with findings consistent with oesophagitis were screened for the presence of Candida oesophagitis by performing KOH (potassium hydroxide) examination and culture on SDA (Sabouraud's dextrose agar). Antifungal susceptibility testing as per CLSI guidelines was performed for fluconazole, a most common empirically prescribed antifungal for the condition. RESULTS: A total of 1868 patients with no known immune-compromised condition underwent upper gastroscopy at our centre during the study period. The prevalence of Candida oesophagitis was 8.7% (n = 163). C. albicans was recovered from majority of infections (52.1%), followed by C. tropicalis (24%), C. parapsilosis (13.4%), C. glabrata (6.9%) and C. krusei (3.6%). Alarmingly, among the C. albicans isolates 8.6% were resistant to fluconazole. CONCLUSION: With rising reports of antifungal drug resistance among the isolates of Candida species, an increasing prevalence of this organism could have an impact on the treatment of Candidal oesophagitis and it should be approached with caution by the clinician.

Application of lipoarabinomannan antigen in tuberculosis diagnostics: current evidence.

Tests based on the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine have emerged as potential point-of-care tests for tuberculosis (TB). We aimed to assimilate the current evidence regarding the diagnostic performance of LAM assays and to ascertain their clinical indication in settings with high and low prevalence of HIV-TB co-infection. Owing to suboptimal sensitivity, the urinary LAM assays are unsuitable as general screening tests for TB. However, unlike traditional diagnostic methods, they demonstrate improved sensitivity in HIV-TB co-infection which further increases with low CD4 counts. Accordingly, these assays are indicated as rule-in tests for TB in patients with advanced HIV-induced immunosuppression, and facilitate the early initiation of antituberculous treatment in them. They also offer incremental sensitivity and specificity when used as adjunct tests to smear microscopy and chest radiography in HIV-TB co-infection. They obviate the biohazards associated with sputum samples and provide an alternative diagnostic tool in sputum-scarce patients. Notwithstanding these advantages, the specificity of these assays is variable, which is mostly attributable to misclassification bias and cross-reactivity with non-tuberculous mycobacteria or other commensal flora. Furthermore, the inability to detect low titres of antigen in HIV-uninfected patients makes these assays unsuitable for use in settings with a low HIV prevalence. Future research targeted towards inclusion of specific monoclonal antibodies and more sensitive immunoassay platforms might help to improve the diagnostic performance of these assays and extend their applicability to the general population of patients with TB.