Clinical characteristics, outcome, and factors associated with mortality of pulmonary mucormycosis: a retrospective single-center study from Pakistan.

Introduction and objective: Pulmonary mucormycosis is a rare but rapidly progressive fatal disease. Limited data exist on the outcomes and factors associated with poor prognosis of pulmonary mucormycosis. The objective of this study was to evaluate clinical characteristics, factors associated with mortality, and outcomes of pulmonary mucormycosis at a tertiary care hospital in Pakistan. Methods: This was a retrospective observational study conducted at a tertiary care hospital in Karachi, Pakistan. Medical records of hospitalized patients diagnosed with proven or probable pulmonary mucormycosis between January 2018 and December 2022 were reviewed. Univariate and regression analyses were performed to identify factors associated with mortality. Results: Fifty-three pulmonary mucormycosis patients (69.8% male) were included, with mean age of 51.19 ± 21.65 years. Diabetes mellitus was the most common comorbidity [n = 26 (49.1%)]. Chronic lung diseases were present in [n = 5 (9.4%)], and [n = 16 (30.2%)] had concurrent coronavirus disease 2019 (COVID-19) pneumonia. The predominant isolated Mucorales were Rhizopus [n = 32 (60.3%)] and Mucor species [n = 9 (17%)]. Main radiological findings included consolidation [n = 39 (73.6%)] and nodules [n = 14 (26.4%)]. Amphotericin B deoxycholate was prescribed in [n = 38 (71.7%)], and [n = 14 (26.4%)] of patients received combined medical and surgical treatment. The median [interquartile range (IQR)] hospital stay was 15.0 (10.0-21.5) days. Intensive care unit (ICU) care was required in [n = 30 (56.6%)] patients, with 26 (49.1%) needing mechanical ventilation. Overall mortality was seen in 29 (54.7%) patients. Significantly higher mortality was found among patients requiring mechanical ventilation 20/29 (69%, p = 0.002). Immunosuppression (p = 0.042), thrombocytopenia (p = 0.004), and mechanical ventilation (p = 0.018) were identified as risk factors for mortality on multivariable analysis. Conclusion: This study provides essential insights into the clinical characteristics, outcomes, and mortality factors associated with pulmonary mucormycosis. The mortality rate was high (54.7%), particularly in patients with immunosuppression, thrombocytopenia, and those who required mechanical ventilation.

A comparative study on the use of procalcitonin to distinguish between central fever and infectious causes of fever.

Introduction: central fever is defined as elevated body temperature without any evidence of infection or drug reaction fever, and currently it has no definitive diagnostic criteria. The current study aims to assess the role of procalcitonin (PCT) in differentiating central fever from fever secondary to infections in patients with neurological insults. Methods: we conducted a retrospective study of patients admitted with a neurological insult (brain trauma, brain tumors and cerebrovascular accidents) in a tertiary care hospital. All patients who developed fever 48 hours after admission and had procalcitonin, C-reactive protein (CRP), and Erythrocyte sedimentation rate (ESR) done as part of fever evaluation were assessed to include in the study. Results: out of 70 patients who met inclusion criteria, 37 had infections identified and 33 had no source of infection. The mean age was 42.9 years (± 18) in the infectious group while 40.3 years (± 18.2) in the central fever group and there was male predominance in both groups. In the infectious group there were 25(67.6%) males vs. 12(32.4%) females while in non -infectious group, males vs. females were 18(54.5%) vs. 15(45.5%) and there was no difference in both group (p-value 0.26) Median procalcitonin (PCT) value was 0.09 ng/dl (IQR 0.05- 0.19) in patients with no identified cause of infection and 1.4 ng/dl (IQR 0.5-5.1) in patients with infections with a p-value of <0.001. Although CRP and ESR were low in patients with central fever as compared to those with infections, these differences did not reach statistical significance with p-value of CRP 0.18 and p-value of ESR 0.31 between two groups. Conclusion: PCT levels were low in patients with central fever and may be considered as a useful biomarker to differentiate between infectious fever from non-infectious fever in patients with brain injury. This can prevent unnecessary antibiotic use in patients without infection.

Association and outcomes of bacterial infections with acute coronary syndrome; a cross-sectional study from a tertiary care hospital in Pakistan.

OBJECTIVE: To identify the association between acute infection and acute coronary syndrome, and to evaluate the outcomes in such cases. METHODS: The cross-sectional, retrospective, analytical study was conducted at the Aga Khan University Hospital, Karachi, from July to December 2020, and comprised data from January to December 2019 of acute coronary syndrome patients aged >18 years. Data related to demographics, comorbidities, smoking status and history of dyslipidaemia. Binary logistic regression was used to explore the association of infections with acute coronary syndrome. Data was analysed using SPSS 26. RESULTS: Of the 1202 patients with acute coronary syndrome, 189(15.7%) had infection before the coronary event. The mean age of the patients was 68.5±12.4 years, and 97(51.3%) of them were females. Community-acquired pneumonia was found in 105(55.6%) patients, followed by urinary tract infection 64(33.9%) and cellulitis 8(4.2%). For pneumonia, the odds of having non-ST elevated myocardial infarction was 1.1 (95% confidence interval: 0.4-3.0). With urinary tract infections, unstable angina was associated with an odd ratio of 4.2 (95% confidence interval: 1-17.4), and ST elevated myocardial infarction was associated with odd ratio of 3.7 (95% confidence interval: 0.4-31). CONCLUSIONS: Bacterial infections were found to be associated with acute coronary syndrome. Bacterial infections with pneumonia and urinary tract infections showed a higher risk of myocardial ischaemia..

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Post-COVID-19 sequelae of the respiratory system. A single-centre experience reporting the compromise of the airway, alveolar and vascular components.

The long-term sequelae of COVID-19 have now become more common and appreciable. The SARS-CoV-2 virus can cause a variety of infectious and non-infectious pulmonary complications. The purpose of this study is to raise awareness about post-COVID-19 pulmonary sequelae, both infectious and non-infectious, in this geographical area. A retrospective study was conducted from July 1st 2020 to December 20th 2020. A total of 1200 patients were evaluated, with 83 suffering from post-COVID-19 pulmonary complications. The patients' mean age was 62 years (IQR 55-69), with 63 (75.9%) being male. The most common co-morbid illnesses were hypertension (49, 59%) and diabetes (45, 54.2%). The majority of them (37, 44.6%) had severe COVID-19, followed by critical COVID-19 (33, 39.8%). There was no statistically significant difference in recurrence of respiratory symptoms or duration of current illness between non-severe, severe, and critical COVID-19 patients. Non-infectious complications were observed in the majority of patients (n=76, 91.5%), including organizing pneumonia/ground glass opacities in 71 (88%) patients, fibrosis in 44 (55%), pulmonary embolism in 10 (12.5%), pneumomediastinum in 6 (7.4%) and pneumothorax in 7 (8.6%). Infective complications (25, 30.1%) included aspergillus infection in 10 (12.0%) and bacterial infection in 5 (8.47%), with more gram-negative infections and one patient developing Mycobacterium tuberculosis. Post COVID-19 mortality was 11 (13.3%). The long-term pulmonary sequelae of COVID-19 are not rare. Cryptogenic organizing pneumonia, ground glass opacities, and fibrosis were common post-COVID-19 sequelae in our patients. This necessitates frequent close monitoring of these patients in order to initiate early appropriate management and prevent further morbidity and eventual mortality.

Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome.

Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.

Severity of COVID-19 in bacillus Calmette-Guérin vaccinated population.

PURPOSE: Considering the cross-protection reported for bacillus Calmette-Guérin (BCG) vaccination on viral respiratory infections, it has been proposed that it could reduce the severity of coronavirus disease 2019 (COVID-19). The objective of the current study is to investigate the association between the severity of COVID-19 with prior BCG vaccination in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MATERIALS AND METHODS: Adult patients (18 years or above) with positive SARS-CoV-2 polymerase chain reaction admitted in July 2020 were included in this cross-sectional study. Patients were classified into non-severe, severe, and critical diseases. History of prior BCG vaccination and the presence of a BCG vaccination scar were recorded. RESULTS: Out of 103 patients, 64 patients with prior history of BCG vaccinations were compared with 39 patients without BCG vaccination in childhood. The median age was 55 years and 64 years in BCG vaccinated & non-BCG vaccinated patients (p-value=0.002). There was male predominance in both groups and frequent comorbid illnesses were hypertension and diabetes mellitus. Severe COVID-19 was found in 91 patients (88.3%) followed by non-severe disease and critical diseases i.e., 7 (6.8%) and 5 (4.9%) patients, respectively. No association of prior BCG vaccination with disease severity of COVID-19 was found in this study and mortality was 8.7%. Out of nine patients who expired only 2 (22.2%) had a prior history of BCG vaccination (p-value=0.01). Secondary infections were present in 26 patients and the majority had pneumonia. CONCLUSION: The BCG vaccine has no impact on the severity of COVID-19 but could have a protective role with a low mortality rate in already infected patients.

Comparison of clinical characteristics and outcomes between COVID-19 pneumonia and H1N1 influenza.

INTRODUCTION: The COVID-19 pandemic has been likened to the 2009 H1N1 influenza pandemic. We aim to study the similarities and differences between patients hospitalized with COVID-19 and H1N1 influenza in order to provide better care to patients, particularly during the co-circulation of Influenza A Subtype H1N1 and SARS-CoV-2. MATERIAL AND METHODS: A retrospective cohort study was conducted in order to compare clinical characteristics, complications, and outcomes of hospitalized patients with PCR-confirmed H1N1 influenza pneumonia and COVID-19 at a tertiary care center in Karachi, Pakistan. RESULTS: A total of 115 patients hospitalized with COVID-19 were compared with 55 patients with H1N1 Influenza A pneumonia. Median age was similar in both COVID-19 patients (54 years) and in patients with H1N1 influenza (59 years), but there was male predominance in COVID-19 patients (OR = 2.95; 95% CI: 1.12-7.79). Patients with COVID-19 pneumonia were 1.34 (95% CI: 1.14-1.62) times more likely to have a greater duration of illness prior to presentation compared to H1N1 influenza patients. COVID-19 patients were 4.59 times (95% CI: 1.32-15.94) more likely to be admitted to a general ward compared to H1N1 pneumonia patients. Moreover, patients with COVID-19 were 7.62 times (95% CI: 2.42-24.00) more likely to be treated with systemic steroids compared to patients with H1N1 pneumonia. The rate of nosocomial infections as well as mortality was similar in both H1N1 and COVID-19 pneumonia. CONCLUSION: Our study found a male predominance and longer duration of illness in hospitalized patients with COVID-19 compared to H1N1 influenza patients but no difference in outcomes with either infection.

Role of awake prone positioning in patients with moderate-to-severe COVID-19: an experience from a developing country.

There is limited evidence on the efficacy of awake prone positioning (PP) in non-ventilated patients with COVID-19 who have hypoxemia. We, therefore, aim to describe our experience with the use of early proning in awake, non-intubated patients with confirmed COVID-19. In our retrospective observational study, 23 patients with confirmed positive PCR test results for Severe Acute respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and hypoxemia that required oxygen therapy with or without non-invasive ventilation were treated with PP. Patients were classified into mild, moderate and severe COVID-19 disease. There were no targeted number of hours for proning per day and patients were kept in prone position according to their tolerance. The primary outcome measure was the avoidance of intubation and secondary outcomes were in-hospital mortality, length of hospital stays and complications related to PP. The mean (standard deviation) age of our cohort was 54.5 (11.7) years, and the majority were males (21/23, 91.3%). Sixty-one per cent (14/23) of the patients were suffering from severe disease and 82.6% (19/23) had bilateral lung involvement with interstitial infiltrates. Majority of the patients were prone positioned for a median of 6 days (IQR 4 - 8). Only one patient required transfer to ICU for mechanical ventilation and subsequently died due to severe ARDS. All 22 patients showed progressive improvement in oxygen requirement and PF ratio, mostly after 3-5 days of proning. The mean length of hospital stay was 12 days. All patients, except one, were discharged in stable conditions, on room air or on a minimal oxygen requirement of 1-2 liters. No major complication of PP was recorded. Awake prone positioning is a valuable and safe therapeutic adjunct that can be applied in patients with moderate-to-severe COVID-19. It can also be included in the home-based management protocols of COVID-19 to improve patient outcomes and mitigate the burden on health care facilities.

Predictors of mortality in hospitalized patients with influenza: a five-year experience from a tertiary care centre in Pakistan.

Influenza outbreaks are associated with significant morbidity. Our aim was to determine the factors associated with increased mortality in hospitalized patients admitted with diagnosis of influenza, at a tertiary care center in Pakistan. This study included all adult patients with an influenza infection, confirmed by realtime reverse-transcriptase polymerase-chain-reaction (RT-PCR) at Aga Khan University Hospital Pakistan. In our study, 112 patients with laboratory-confirmed influenza virus infection were admittedat our hospital from the 1st of January 2013 to the 31st of December 2018. Eighty-nine patients (79.46%) were managed in ward or special care units and 23 patients (20.5%) received treatment in intensive care unit (ICU). The overall mortality in our study was 15/112 (13.4%) with the mortality rate of ICU patients being 47.8% while the mortality rate of patients treated in special care units and wards was only 4.5%. The mean age of patients with influenza infection was 58.1 years (±16.6). Influenza virus type A was found in 87 patients (77.6%), while influenza type B was present in only 25 (22.4%) patients. Out of the 15 non-survivors, 14 had influenza A. Only 17 patients (15.2%) were found to have positive culture of respiratory specimen, out of which 3 were non-survivors and 14 were survivors. Our analysis identified septic shock (odds ratio 45.24; 95%, confidence interval 6.20-330; p<0.001), renal failure (odds ratio 10.88; 95%, confidence interval 1.61-73.52; p=0.01) and ICU stay (odds ratio 17.22; 95%, confidence interval 2.68-110.5; p=0.003) as independent risk factors associated with in-hospital mortality.

Stenotrophomonas maltophilia Meningitis - A Case Series and Review of the Literature.

Stenotrophomonas maltophilia is an infrequent cause of acute bacterial meningitis and only a few cases have been reported in the literature. Infection is associated with morbidity and mortality, and its optimal management remains ill-defined. The aim of the current study is to review the management of S. maltophilia meningitis. We described two cases of S. maltophilia meningitis following neurosurgical procedures. The first patient was a 60-year-old female. She was admitted to the hospital with a left basal ganglia bleed and underwent placement of an external ventricular drain for the treatment of hydrocephalus. She developed S. maltophilia meningitis 20 days after surgery. She was successfully treated with a combination of trimethoprim-sulfamethoxazole and intravenous colistin and the removal of the drain. She successfully underwent a ventriculoperitoneal (VP) shunt placement at the therapeutic midway point. The second patient was a 35-year-old male with a history of intracranial aneurysm bleeding. He had undergone a craniotomy and placement of a ventriculoperitoneal shunt two years previously. His shunt was replaced twice due to blockage. The last replacement had occurred 15 days prior to the development of meningitis. He was treated with a combination of trimethoprim-sulfamethoxazole and ceftazidime (as well as undergoing another shunt replacement) and experienced an excellent recovery. S. maltophilia is a rare but important cause of nosocomial meningitis. It is strongly associated with prior hospitalization and neurosurgical intervention, which is also found in our case series. The management of S. maltophilia meningitis is a therapeutic challenge due to its high resistance to multiple antibiotics. Optimal therapy is based on antimicrobial sensitivity, and the trimethoprim-sulfamethoxazole-based combination has been shown to be successful. The duration of therapy is debatable, but like most gram-negative meningitis infections, therapy lasting up to three weeks appears to be adequate.

Knowledge, attitude and perception survey of doctors regarding antibiotic use and resistance in Karachi, Pakistan.

OBJECTIVE: To establish a better understanding of physicians' knowledge and beliefs, and to compare distinctions in knowledge, attitude and perception of junior and senior doctors regarding rational use of antibiotics. METHODS: The cross-sectional study was conducted at a tertiary care hospital in Karachi, from June 1 to July 31, 2016, and comprised senior and junior doctors. A 26-item questionnaire divided in three sections was used to test knowledge, attitude and perception of the subjects regarding rational use of antibiotics. Data was analysed using SPSS 23. RESULTS: Of the 200 subjects, 132(66%) were senior doctors; 68(34%) were junior; 116(58%) were females; 84(42%) were males; and the highest number of respondents were from General Medicine 65(32.5%). While 182(91%) doctors realised that antibiotic resistance was a pressing issue, only 131(65.5%) felt confident about their prescriptions and 94(47%) admitted that they over-prescribed antibiotics. Among young physicians, 13(19.1%) believed that antibiotics did not cause side effects even when prescribed unnecesarily. Also, 47(69.1%) junior doctors felt that patients' demands influenced their prescriptions compared to 66(50%) senior doctors (p=0.01). CONCLUSIONS: Although physicians were found to be knowledgeable about rational use of antibiotics, there were gaps in knowledge and perception.

Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in an immunocompetent patient: A case report and review of literature.

BACKGROUND AND PURPOSE: Rhinocladiella mackenziei is a neurotropic fungus, which can cause devastating intracerebral infections with up to 100% fatality rate. It is difficult to isolate this fungus in laboratory as it grows slowly and requires diagnostic skills. CASE REPORT: A 42-year-old Pakistani man presented with headache, facial numbness, progressive upper limb weakness, and dysarthria. Magnetic resonance imaging of the brain showed a space-occupying lesion in the basal ganglia region. The patient underwent supratentorial craniotomy for biopsy and excision. Histopathology of the specimen revealed granulomatous inflammation with abscess formation. Periodic acid- Schiff special stains highlighted the presence of numerous septate fungal hyphae. The results revealed the growth of dematiaceous fungi, which were morphologically classified as R. mackenziei. The patient is currently stable and is being on amphotericin and posaconazole, along with neurorehabilitation therapy. CONCLUSION: Rhinocladiella mackenziei brain abscess is a devastating infection with significant mortality. This condition should be suspected in patients with brain abscess from high endemic areas.

Tocilizumab for COVID-19 Acute Respiratory Distress Syndrome: Outcomes Assessment Using the WHO Ordinal Scale.

Introduction Cytokine release syndrome in COVID-19 is characterized by hyperinflammation, which manifests as acute respiratory distress syndrome (ARDS), multiorgan failure, and high inflammatory parameters. Tocilizumab, an interleukin 6 (IL-6) antagonist has been used in COVID-19 ARDS with conflicting results from different parts of the world. Objective To study the treatment outcomes with tocilizumab in patients with COVID-19 ARDS and hyperinflammation using the World Health Organization (WHO) COVID-19 ordinal scale. Methods An observational study was conducted from Feb 2020 to May 2020 on COVID-19 ARDS patients with hyperinflammation. Results A total of 244 patients with COVID-19 were admitted, out of which 107 had ARDS. Thirty patients had both ARDS and hyperinflammation and received tocilizumab. The mean age was 62.5 years (SD: 13.5) and the majority were male (83%). The mean CRP pre-treatment was 217.5 mg/L and post 48 to 72 hours of tocilizumab treatment was 98.5 mg/L. Twenty-one patients (70%) also received concomitant intravenous (IV) methylprednisolone. Of the 30 patients, seven died and 20 recovered. Ten patients required intensive care unit admission and nine developed nosocomial infections. COVID-19-associated aspergillosis was diagnosed in three patients post tocilizumab treatment. Mortality was significantly higher in patients who developed a nosocomial infection and who required intermittent positive pressure ventilation (IPPV). Post-treatment, clinical improvement was observed in patients who had a median score of 5 on the WHO ordinal scale. Conclusion Our study supports the use of tocilizumab in COVID-19 ARDS patients with a pre-treatment median WHO ordinal severity score of 5 and recommends the monitoring of nosocomial infections and opportunistic infections.

Enterococcal Meningitis/Ventriculitis: A Tertiary Care Experience.

CONTEXT: Enterococcal meningitis is very rare among bacterial meningitis and has variable clinical outcomes. AIMS: The purpose of the current study is to evaluate clinical features, therapeutic options with susceptibility profile, and outcomes of enterococcal meningitis in a tertiary care hospital. SETTINGS AND DESIGN: We retrospectively reviewed medical records of all patients with enterococcal meningitis over the periods of 4 years. SUBJECTS AND METHODS: The clinical and laboratory data of all patients with enterococcal meningitis were evaluated between 2013 and 2016. RESULTS: Six cases of enterococcal meningitis were found (three infant and three adults). All patients developed meningitis after neurosurgical procedures, and majority of patients (four out of six) had central nervous system (CNS) devices in situ at the time of development of meningitis. The causative organism isolated from cerebrospinal fluid (CSF) culture of all patients was Enterococcus species only. All Enterococcus spp. were resistant to ampicillin, Amoxicillin-clavulanate, and oxytetracycline and two isolates were also resistant to vancomycin. Four patients with vancomycin-sensitive Enterococcus spp. were treated with vancomycin alone for mean periods of 18 days (14-21 days). One patient with vancomycin-resistant Enterococcus (VRE) meningitis was treated with linezolid alone, and another one requires combination with rifampicin to achieve microbiological clearance of CSF. CNS devices were removed in all patients. No mortality was reported in current case series. CONCLUSIONS: Enterococcal meningitis is very uncommon, mostly associated with neurosurgical intervention. Early treatment is associated with favorable outcomes. Removal of CNS devices is recommended to achieve a clinical cure.