Successful treatment of sino-pulmonary infection & skull base osteomyelitis caused by New Delhi metallo-ß-lactamase-producing Pseudomonas aeruginosa in a renal transplant recipient by using an investigational antibiotic cefepime/zidebactam (WCK 5222).

A case of sino-pulmonary infection with skull base osteomyelitis due to XDR-Pseudomonas aeruginosa in renal transplant recipient was successfully treated with investigational antibiotic, cefepime/zidebactam (WCK 5222). This case highlights challenges in managing XDR-pseudomonal infection where source control was infeasible, antibiotic options were extremely limited and individualized dose adjustments were needed.

Post covid cerebral phaeohyphomycosis by Rhinocladiella mackenziei: An unusual association.

Cerebral phaeohyphomycosis (CP) is a rare but a highly morbid fungal infection of the central nervous system caused by the fungi belonging to the order Chaetothyriales, which includes Cladophialophora bantiana, Exophiala dermatitidis, Rhinocladiella mackenziei (RM) etc. This disease is associated with poor clinical outcomes, with reported mortality of over 80%. We present the case of a 65-year gentleman who developed CP secondary to RM infection following COVID-19 and the associated challenges in his medical and surgical management.

A fatal misidentification: Burkholderia pseudomallei misidentified as Acinetobacter spp.

A middle-aged uncontrolled diabetic with chronic kidney disease presented with high-grade fever, skin abscesses and cough for two weeks. His blood cultures grew Burkholderia pseudomallei. A few weeks prior, blood cultures drawn for PUO workup elsewhere grew an organism identified as Acinetobacter sp with an unusual susceptibility pattern. His fever responded to a short course of meropenem. In retrospect, the earlier blood culture had likely misidentified B.pseudomallei as Acinetobacter sp given the background history, risk factors and the peculiar susceptibility report. Through this case, we discuss important aspects of melioid diagnostics which may be clinically relevant to establish this diagnosis.

Ceftazidime-resistant Burkholderia pseudomallei masquerading as isolated atypical neuromelioidosis.

A middle-aged recently diagnosed uncontrolled diabetic from Mumbai, India presented with fever and headache for 8 weeks. Two weeks prior to his symptoms, he travelled to Lonavala during the monsoons and gave history of indoor swimming in a chlorinated pool. Investigations showed isolated neurological involvement with multiple brain abscesses. Abscess cultures grew a non-lactose fermenter. Automated systems failed to identify it. After assessment of his background history and detailed microbiological analysis of the organism, specific investigations were requested which confirmed the suspected diagnosis of melioidosis. We report an unusual presentation of ceftazidime-resistant Burkholderia pseumodmallei as isolated neuromelioidosis with brain abscesses.

Second Ray Amputation in Diabetic Foot - Functionally Better than Proximal Foot Amputations, but Beware of Charcot Arthropathy: A Case Report and Review of Literature.

Introduction: Lower limb amputations secondary to diabetic foot infection/osteomyelitis (OM) are the most common cause for non-traumatic amputations of the lower extremity. Hind/midfoot amputations are commonly done for metatarsal (MT) OM. They are, however, associated with higher complication and revision rates and often lead to below knee amputation. In comparison, distal/forefoot toe disarticulation/ray amputation (R amp) have lesser revision rates/complications and give better functional outcome. Here, we report a case of 2nd R amp with an uncommon complication. Case Report: A 42-year-old male with uncontrolled diabetes and bilateral diabetic neuropathy presented with discharging sinus over plantar aspect of the left foot since 1 week. There was no evidence of underlying OM on MRI. Wound healed with soft-tissue debridement and empirical antibiotics (culture negative) for 2 weeks. Re-debridement was done for a wound gape 6 weeks later. Infection resolved with targeted antibiotics (oral ciprofloxacin and doxycycline) for Enterobacter cloacae given for 1 month. Six months later, he developed pain and swelling in the left foot following prolonged barefoot walking and possible injury with a stone. There was local redness, swelling, and a plantar sinus. MRI revealed septic arthritis of the left 2nd metatarsophalangeal (MTP) joint, OM of the 2nd MT head, and an encapsulated soft-tissue abscess. Aggressive debridement with 2nd R amp and careful separation of encapsulated abscess was done leaving behind base of 2nd MT to maintain stability of the Lisfranc joint. Wound healed primarily. Targeted antibiotics for Methicillin Susceptible Staphylococcus aureus were given for 6 weeks. Good diabetic control and avoiding bare foot walking were advised and he is infection free, fully functional, and asymptomatic at 36 months. However, he was noted to have developed valgus deformity of the midfoot secondary to Charcot osteoarthropathy of the Lisfranc joints at 36 months follow-up, involving 1st, 3rd, and 4th TMT joints. The other foot did not show any evidence of Charcot arthropathy. Conclusion: Recurrent wound infections with subsequent OM are a common feature of diabetic foot. R amps have better functional outcomes with preserved foot stability, shorter length of hospitalization, and associated costs as compared to hind/midfoot amputations. They may, however, develop Charcot osteoarthropathy due to the void between adjoining MTs resulting in altered forces across the Lisfranc joints. Surgeons must beware of this complication, especially following R amps and monitor these patients with serial clinical and radiographic examination.

Melioidosis: Missed opportunities and opportunistic pathogens.

A 31-year Indian homemaker, known to have Systemic Lupus Erythematosus (SLE) and lupus nephritis, was admitted previously in another medical care unit with fever, hemoptysis, arthralgia, and joint swelling. She had been treated with antibiotics and corticosteroids for probable diffuse alveolar hemorrhage (DAH) with clinical and radiological resolution. She was readmitted one month later for similar complaints. Her autoimmune workup revealed evidence of active lupus. Her chest imaging showed the presence of well-circumscribed macronodular lesions with halo sign, but Bronchoalveolar Lavage (BAL) cultures and serum galactomannan were negative. BAL tested positive for hemosiderin-laden macrophages. She was treated with corticosteroids, plasmapheresis, and empiric antibiotics with partial clinical response. One week later, her fever recurred, and she developed new-onset myositis. Bactec blood cultures grew Burkholderia pseudomallei. She received treatment for 3 months with good clinical and radiological resolution. In hindsight, a CT-guided biopsy of the lung lesion may have provided an earlier diagnosis of melioidosis.

Salvaging lives in carbapenem-resistant Gram-negative osteoarticular and soft tissue infections: early compromises save lives.

PURPOSE: Incidence of carbapenem-resistant Gram-negative infections has risen alarmingly all across the globe, both in developed and developing countries alike. The purpose of this study was to assess whether challenges of life-threatening infections with very high resistance pattern can be successfully addressed by a modified approach. METHODS: This is a retrospective study of 26 patients with osteoarticular and soft tissue infections with carbapenem-resistant Gram-negative bacilli treated between 2001 and 2017 with at least two year follow-up after stopping antibiotics. All were treated by a multispecialty team approach with primary aim of "source control at the earliest and avoiding recurrence at all cost". The protocol involved opting for early compromises especially in at "risk individuals", such as resorting to early amputations, especially if salvage meant multiple bony and soft tissue reconstructive procedures, explanation of prosthesis than staged revision, avoiding internal fixations, opting for shortest possible time in external fixators with reshaping and telescoping bone ends to get bony stability and increase surface area even if it meant compromising length. RESULTS: There were five amputations, two excision arthroplasty of hip, many minor but acceptable malunions and shortening. However, lives of 24/26 patients could be salvaged, much better than most of the published data. The two patients who died had peri-prosthetic joint infection after total hip arthroplasty and presented very late in sepsis and died within days of explantation. Infection remission could be achieved in remaining patients. CONCLUSION: These "risk to life" cases can be successfully treated by lowering the aims and expectations from "excellent function to salvage of life and infection remission". Therein lies the "success" in these complex high-risk cases.

Increased frequency of pneumothorax and pneumomediastinum in COVID-19 patients admitted in the ICU: A multicentre study from Mumbai, India.

BACKGROUND: There are limited data regarding the incidence of pneumothorax in COVID-19 patients as well as the impact of the same on patient outcomes. METHODS: A retrospective review of the medical records at three large tertiary care hospitals in Mumbai was performed to identify patients hospitalised with COVID-19 from March 2020 to October 2020. The presence of pneumothorax and/or pneumomediastinum was noted when chest radiographs or CT scans were performed. Demographic and clinical characteristics of patients who developed air leak were recorded. RESULTS: 4,906 patients with COVID-19 were admitted, with 1,324 (27%) having severe COVID-19 disease. The overall incidence of pneumothorax and/or pneumomediastinum in patients with severe disease was 3.2% (42/1,324). Eighteen patients had pneumothorax, 16 had pneumomediastinum and 8 patients had both. Fourteen patients (33.3%) developed this complication breathing spontaneously, 28 patients (66.6%) developed it during mechanical ventilation. Overall mortality in this cohort was 74%, compared with 17% in the COVID-19 patients without pneumothorax (p<0.001). CONCLUSIONS: Our study demonstrates that air leaks occur with a higher frequency in patients with COVID-19 than in other ICU patients. When present, such air leaks contributed to poor outcomes with almost 74% mortality rates in these patients.

Reinfection in COVID-19: A scoping review.

Reinfections in COVID-19 are being reported all around the world and are a cause for concern, considering that a lot of our assumptions and modeling (including vaccination) related to the disease have relied on long-term immunity. We were one of the first groups to report a series of 4 healthcare workers to have been reinfected. This review article reports a scoping review of the available literature on reinfections, with a discussion of the implications of reinfections.

Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis, India.

During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.

Tale of compounding oddities.

We present a case of a 59-year-old man, who on being evaluated for abdominal pain and headache, was found to have a pancreatic head mass and inflammatory hypophysitis. Xpert MTB/Rif of the pancreatic mass biopsy showed the presence of tuberculosis (TB) with a very low load, and rifampicin resistance was detected with absence of probes A and B. Pyrosequencing (a novel genotypic test for TB) of the Xpert MTB/Rif isolate detected a single, rare, high-confidence mutation (S512T) in the rpoB region (rifampicin resistance determining region in the MTB genome). The TB mycobacteria growth indicator tube (TBMGIT) phenotypic drug susceptibility test (DST), however, showed rifampicin susceptibility. Incidentally, he was unable to tolerate rifampicin and responded well to a non-rifampicin-based regimen. We discuss a possible hypothesis of the Xpert-DST discordance in accordance with a recent literature review on phenotypic DST methods. We also discuss the utility of pyrosequencing in clinical practice for the diagnosis of TB and its resistance patterns.

Evaluation of CSF pyrosequencing to diagnose tuberculous meningitis: A retrospective diagnostic accuracy study.

BACKGROUND: We evaluated the performance of pyrosequencing, a genotypic test which detects TB and XDR-defining mutations within 6 h, directly on CSF samples for diagnosing TB meningitis(TBM). METHODS: This retrospective, diagnostic accuracy study was conducted in Hinduja hospital, Mumbai from May-2017 to May-2019. 107 consecutive patients with physician-suspected TBM for whom CSF pyrosequencing was requested were screened. Seven patients with incomplete data were excluded. Diagnostic accuracy of pyrosequencing was compared with Xpert MTB/Rif and TBMGIT (TB Mycobacterial Growth Indicator Tube) culture against the uniform case definition of definite or probable TBM. Susceptibility concordance rate of pyrosequencing with TBMGIT culture and Xpert MTB/Rif was determined. RESULTS: The study cohort comprised of 100 patients[Definite(n = 33), Probable(n = 20), Possible(n = 30), Alternative(n = 17)] with 50% males[median age(years):38(Range:2-87)]. Against the uniform case definition, pyrosequencing had 98·11%(95%CI 89·93-99·95; n = 52/53) sensitivity and 97·79%(86·31-99·67; n = 44/45) negative predictive value(NPV) compared with 43.39%(29·83-57·72; n = 23/53,p < 0.0001) sensitivity and 61.04%(55·31-66·48; n = 47/77) NPV for Xpert MTB/Rif and 45·28%(31·56-59·55; n = 24/53,p < 0.0001) sensitivity and 61·84%(55·92-67·43; n = 47/76) NPV for TBMGIT culture. Susceptibility concordance rate of pyrosequencing with phenotypic Drug Susceptibility Testing was 91.3%(n = 21/23) and with Xpert MTB/Rif was 95·45%(n = 21/22). CONCLUSION: CSF pyrosequencing is significantly more sensitive than Xpert MTB/Rif and TBMGIT culture for diagnosing TBM. Additionally, it facilitates early therapeutic decision-making by providing information on XDR-defining mutations.

Successful treatment of disseminated granulomatous aspergillosis in an apparently immunocompetent host.

A young Indian man presented elsewhere with a short history of haematuria and cough. Investigations revealed renal and pulmonary lesions. Histopathology of these lesions was reported as mucormycosis. He consulted us two months after onset of symptoms, asymptomatic and clinically well, having received no treatment. In view of clinico-histopathological discordance, a review of the biopsy slides was advised but the patient refused further work-up at that time. One week later, however, he was admitted with left hemiparesis. Brain imaging showed an abscess. He underwent surgical excision of the brain abscess and nephrectomy. Review of previous slides showed septate fungal filaments with granulomatous inflammation. Intraoperative cultures grew Aspergillus flavus. He received voriconazole for one year and is well at his two-year follow-up. His immunological work-up was negative for immunodeficiency. This case illustrates that granulomatous aspergillosis may be an indolent infection in apparently normal individuals and reiterates the importance of interpreting diagnostic reports in conjunction with clinical features.

Implications for Diagnosis and Treatment of Infective Endocarditis: Eight year Experience of an Infectious Disease Team in a Private Tertiary Care Centre.

Background: The profile of Infective endocarditis (IE) has been evolving continuously. Like other infectious Diseases (ID) syndromes, IE has not escaped from antibiotic resistance issues. The aim of this study was to determine the implications for diagnosis and treatment by studying the clinical profile and outcome of patients admitted with IE in a tertiary care centre in Mumbai during the period from 2007-2015. Methods: 53 patients having definite or possible IE as per Modified Duke's Criteria (MDC), that were referred to the ID division, were included in this study. Results: 44 (83%) patients had definite IE and 9 (17%) patients had possible IE. 77.4% of the patients were above 40 years of age. 3 patients presented as euthermic IE. Vegetations were not seen on transthoracic echocardiography (TTE) in 3 patients and were seen only on transesophageal echocardiography (TEE). 15 patients had prosthetic valve IE. 7 patients had rheumatic heart disease. 3 patients had bicuspid aortic valve and 4 had ventricular septal defect (VSD). The rest had no apparent underlying heart disease (45.3%). 41 patients (77.3%) had culture-positive IE and 12 patients (22.6%) had culture-negative IE. Streptococcus spp. was found in 14 (26.4%) patients, Enterococcus spp. in 9 patients (17%). Other organisms isolated were methicillin-sensitive S. aureus (3), Methicillin Resistant S. aureus (1), Eikenella corrodens (1), B. cepacia (2), Salmonella Typhi (1), P. aeruginosa (1), M. abscessus (2) and other rapidly growing mycobacteria (RGM) (5), Candida parapsilosis (1), Candida pelliculosa (1) and Aspergillus fumigatus (1). Notably there was only one case of MRSA. Among the Streptococcus spp., Penicillin MIC testing was done in 11 cases of the 14 cases of Strep spp. 3 of them showed intermediate resistance and 2 were resistant. Among enterococcal IE, 3 had high level aminoglycoside resistance (HLAR) and 2 had ß-lactamase producing enterococci with HLAR and 1 had Vancomycin resistance. These were successfully treated with combinations of Ampicillin with Ceftriaxone, Ampicillin-Sulbactam with Imipenem and Daptomycin respectively. The only case of MRSA prosthetic valve endocarditis was successfully treated with Vancomycin and Rifampicin in addition to surgery. Surgery for IE was performed in 26 out of 53 (49%) patients. Early valve surgery (within 15 days of hospital admission) was performed in 6 of these 26 patients. . Conclusion: There is a change in the spectrum and antimicrobial susceptibility of organisms causing IE. We encountered several difficulties with the use of the MDC as 43.5% patients had no predisposing factors for IE and blood cultures were negative in 22.6% cases. In our study, PVE was the most common predisposing condition for IE. VGS followed by enterococci were found to be the commonest cause for IE in our setting. Both organisms show variable drug resist patterns. MRSA was isolated in 1 patient only. Thus vancomycin may not be required as empiric treatment in our setting. This is important from the perspective of antimicrobial stewardship Good infection control practices are essential to prevent nosocomial IE due to pathogens such as non-tuberculous mycobacteria (NTM). Important changes in the disease characteristic, treatment, and outcome are noted. Surgery, whenever indicated, helps in improving outcome in these patients thus reiterating the need for a team approach for optimal management of this complex, challenging condition..

Aspergillus Osteomyelitis of the Ribs in Immunocompetent Hosts: Report of Two Rare Cases.

INTRODUCTION: Osteomyelitis is rarely caused by fungi, most common among them being Candida. Aspergillus is a rare cause of fungal osteomyelitis mimics tuberculous osteomyelitis. Aspergillus osteomyelitis (AO) of the ribs is relatively uncommon, with an incidence rate of only 9% among all reported cases of AO. With mortality rates of almost 25%, AO is on the rise attributed to increasing numbers of immunocompromised individuals. There are very few case reports of AO of ribs in immunocompetent individuals. We report two such cases. CASE REPORT: Case 1: A 51-year-old male developed spontaneous chest pain along right costal margin with a low-grade fever. High-resolution computed tomography chest revealed osteomyelitis of anterolateral chest wall. He did not improve with empirical antitubercular therapy, and subsequent debridement showed polymicrobial pyogenic infection which was managed with appropriate antibiotics elsewhere. Samples were not sent for fungal culture. He presented to us 3 months later, and surgical debridement showed growth of Aspergillus flavus which was managed with oral voriconazole. The lesion healed with no recurrence at 24-month follow-up. Case 2: A 40-year-old male presented to our institute with left-sided chest pain, low-grade fever, and loss of appetite. There was a history of injury with a sharp piece of wood 2 years earlier. Magnetic resonance imaging defined the lesion which was biopsied under ultrasound guidance. Cultures grew A. flavus which was treated with oral voriconazole. He had complete clinical improvement at 16-month follow-up. CONCLUSION: More number of AO cases are being reported in immunocompetent individuals. Variability in clinical picture, rarity, misdiagnosis, empirical therapy, and failure to send deep tissue samples for fungal cultures are some of the reasons for the high mortality rates. It is paramount in today's scenario of atypical presentations, to obtain deep tissue for all cultures including fungal culture and histopathology, either surgically or under image guidance to achieve good clinical outcomes. Our study highlights that following the strict protocol of obtaining tissue for fungal culture, systemic antifungal therapy, and surgical debridement where necessary can help to diagnose and treat this rare pathology and ensure the good clinical outcome.

Intravascular Stent-related Endocarditis due to Rapidly Growing Mycobacteria : A New Problem in the Developing World.

We report five patients with infective endocarditis (IE) due to rapidly growing mycobacteria (RGM) which we postulate are related to the reuse of percutaneous transluminal angioplasty balloon catheters prior to the intravascular stent placement. The index procedure was performed at various institutes in different parts of the country. We call attention to diagnostic and therapeutic difficulties and the uniformly dismal outcome of RGM IE as well as the potential hazards of re-use of single-use devices.