Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Indian Academy of Pediatrics Consensus Statement on Diagnosis and Management of Bone and Joint Infections in Children.

JUSTIFICATION: Osteoarticular infections are fairly common in children but often these are associated with underdiagnosis, delayed diagnosis and improper management. This leads to an increased incidence of complications and poor outcomes. Given the paucity of standard protocols for the management of these children in the Indian context, Indian Academy of Pediatrics (IAP) has taken the initiative to formulate guidelines for the early diagnosis and rational management of bone and joint infections (BJIs). OBJECTIVES: To critically evaluate the current evidence and formulate consensus guidelines for the diagnosis and management of BJIs in children. PROCESS: A committee comprising of eminent national faculty from different parts of the country who are experts in the field of Pediatric Infectious Diseases, Pediatric Orthopedics and Musculoskeletal Radiology was constituted and duly approved by the IAP. On Jan 16, 2021, a virtual meeting was held and a detailed discussions were carried out regarding the need to formulate these guidelines. Subsequently, the expert group defined the key questions in the first stage followed by collection and review of scientific evidences including available national and international recommendations or guidelines. This was followed by detailed deliberation among group members and presentation of their recommendations. The same were finalized in an online meeting on Aug 01, 2021, and a consensus statement was developed and adopted by the group. STATEMENT: BJIs are medical emergencies that need early diagnosis and appropriate therapy to prevent long term sequelae like limb deformities. Bacterial infections like Staphylococcus aureus is the most common etiological agent. Nonspecific and subtle clinical manifestations make the diagnosis of pediatric BJIs more challenging. Diagnosis of BJIs is primarily clinical, supplemented by laboratory and radiological investigations. The choice of antibiotic(s), mode of administration and duration of therapy requires individualization depending upon the severity of infection, causative organism, regional sensitivity patterns, time elapsed between onset of symptoms and the child's presentation, age, risk factors and the clinical and laboratory response to treatment. There is paucity of appropriate guidelines regarding the diagnosis and management of BJIs in children in Indian context. Hence, the need for this expert consensus guidelines in Indian settings.

What is New in the Diagnosis of Childhood Tuberculosis?

The fact that almost half of the 1 million cases of childhood tuberculosis (TB) globally remain undiagnosed jeopardizes the TB elimination goal. Fortunately, there are new advances in this field which have the potential to bridge this diagnostic gap. Advances in imaging include computer assisted interpretation of chest X-rays (CXRs), point of care ultrasound (POCUS) and faster and superior computed tomography/ magnetic resonance imaging (CT/ MRI) protocols. The urine lipoarabinomannan test has proved to be a good point of care test for diagnosing TB in Human immunodeficiency virus (HIV) infected children. Stool and nasopharyngeal aspirates are emerging as acceptable alternatives for gastric lavage and induced sputum for diagnosing intrathoracic tuberculosis. Xpert MTB/RIF Ultra has improved sensitivity compared to Xpert MTB/RIF for diagnosing both pulmonary/ extrapulmonary TB. Xpert XDR is another commercially available accurate point of care test for detecting resistance to drugs other than rifampicin in smear positive samples. Other molecular methods including new line probe assays, pyrosequencing, whole genome sequencing, and targeted next generation sequencing are extremely promising but not available commercially at present. The C-Tb skin test is an acceptable alternative to the tuberculin skin test and interferon gamma release assays for diagnosis of latent infection. There is an urgent need to incorporate some of these advances in the existing diagnostic algorithms of childhood TB.

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India.

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

Burkholderia cepacia complex as a cause of community acquired bacteremia in a young immuncompetent male.

Burkholderia cepacia complex (BCC) is a well-recognized cause of nosocomial infections. We describe here a young healthy male who presented with fever and chest pain with ECG changes of acute pericarditis. Two sets of blood cultures at separate timings grew gram negative bacilli identified as BCC by molecular methods. The patient responded to intravenous ceftazidime despite high ceftazidime MIC's. The source of infection was probably contaminated nasal spray/nasal saline wash which he used after a balloon sinoplasty procedure one month ago. Issues related to accurate identification and susceptibility testing of BCC are also discussed.

Target product profiles for diagnosis of sepsis: Proposing a new approach for diagnostic innovation.

Background & objectives: Sepsis, including neonatal sepsis, remains a prevalent cause of morbidity and mortality in low- and middle-income countries such as India, representing 85 per cent of all sepsis-related deaths globally. Early diagnosis and timely initiation of treatment is challenging due to non-specific clinical manifestations and non-availability of rapid diagnostic tests. There is an urgent need for affordable diagnostics with fast turnaround time catering to the needs of end-users. Target product profiles (TPPs) have been found instrumental in developing 'fit-for-use' diagnostics, thus reducing the time taken to facilitate development and improving diagnosis. Hitherto, no such guidance or criteria has been defined for rapid diagnostics for sepsis/neonatal sepsis. We propose an innovative approach for developing the diagnostics for sepsis screening and diagnosis which can be utilized by diagnostic developers in the country. Methods: Thr@ee-round Delphi method, including two online surveys and one virtual consultation, was adopted to define criteria for minimum and optimum attributes of TPPs and build consensus on characteristics. Expert panel (n=23) included infectious disease physicians, public health specialists, clinical microbiologists, virologists, researchers/scientists and technology experts/innovators. Results: We present a three-component product profile for sepsis diagnosis, (i) screening with high sensitivity, (ii) detection of aetiological agent, and (iii) profiling of antimicrobial susceptibility/resistance, in adults and neonates with an option of testing different considerations. An agreement of >75 per cent was achieved for all TPP characteristics by Delphi. These TPPs are tailored to the Indian healthcare settings and can also be extrapolated to other resource-constraint and high-disease burden settings. Interpretation & conclusions: Diagnostics developed using these TPPs will facilitate utilization of invested resources leading to development of the products that have potential to ease the economic burden on patient and save lives.

A case of Kytococcus schroeteri prosthetic valve endocarditis in a patient with COVID-19 infection.

64 years old male presented fever, gastrointestinal symptoms, COVID-19 infection with bioprosthetic mitral in situ, cardio embolic stroke 2 years ago. The 2 D ECHO showed a vegetation indicating infective endocarditis. Three paired blood cultures grew Kytococcus schroeteri. The organism was sensitive to Vancomycin, Teicoplanin, Gentamycin and Linezolid. Patient had multiorgan dysfunction which further deteriorated into failure, disseminated intravascular coagulation resulting into death of the patient.

The mystery behind a 1000 day fever in a young male.

This case is of a 23 year old diabetic male who presented with fever and splenic lesions. He continued to have fever off and on over the next 3 years despite empirical antibiotics and anti-tubercular therapy. No definitive diagnosis could be made despite exhaustive investigations. Finally, a splenectomy resulted in sustained defervescence. The splenic histopathology showed caseating granulomas but aerobic cultures, Xpert MTB/Rif ULTRA, TB and fungal cultures were negative. A final diagnosis of splenic melioidosis was made based on the clinical features, radiology, histopathology, literature review and absence of an alternative diagnosis.