Correlation between lung function tests and peak oxygen consumption in post-TB lung disease.

BACKGROUND: After TB treatment, many patients have post-TB lung disease (PTLD), associated with increased mortality and morbidity. Nevertheless, relationships between lung function testing and exercise capacity in people with PTLD are poorly understood.METHODS: This single-centre study investigated the association between lung function testing and peak oxygen consumption (VO2peak) and percentage-predicted VO2peak (VO2peak (%pred)) in adults with PTLD investigated for surgery.RESULTS: Eighty-two patients (52 males, 30 females) with a mean age of 43.2 years (SD 11.3) were included. Spirometric values of forced vital capacity (FVC) percentage predicted (%pred) and forced expiratory volume in 1 sec (FEV1) %pred suggested significant correlations with VO2peak (%pred) (P < 0.001 and P < 0.001), whereas FEV1/FVC did not. Diffusing capacity for carbon monoxide (DLCO) %pred also correlated significantly with VO2peak (%pred) (P = 0.002). However, the magnitude of all significant correlation coefficients were weak. No significant correlations for any plethysmographic values with VO2peak (%pred) could be robustly concluded. Correlations with VO2peak (ml/kg/min) for most physiological variables were less robust than for VO2peak (%pred).CONCLUSIONS: Although statistically significant, the correlations between any measure of lung function and VO2peak or VO2peak (%pred) were weak, with only FVC correlation coefficient surpassing 0.50.

Corticosteroids in critical COVID-19: Are all corticosteroids equal?

BACKGROUND: The hyperinflammation seen as part of a dysregulated immune response to SARS-CoV-2 in its most severe form leads to acute respiratory distress syndrome (ARDS), multiorgan failure and death. Corticosteroid therapy targets this hyperinflammation, otherwise known as a cytokine storm. It is the only therapeutic agent to date with a mortality benefit, with clear guidelines from national and international health authorities guiding its use. Objectives. To compare severity-of-illness indices, survival, length of intensive care unit (ICU) stay and potential ICU complications in patients treated with different corticosteroid regimens (high-dose hydrocortisone, high-dose methylprednisolone and lower-dose dexamethasone). Methods. In this single-centre descriptive retrospective observational study of a cohort of patients with severe COVID-19 admitted to a COVID-dedicated ICU, we compared patients treated with the three different corticosteroid regimens. Results. In 242 cases we could not demonstrate any statistically or clinically significant difference in the outcome of patients with critical COVID-19 treated with high-dose intravenous hydrocortisone (n=88) or methylprednisolone (n=46) compared with a relatively lower dose of dexamethasone (n=108). The survival rates were 38.6%, 39.1% and 33.3%, respectively (p=0.68). Patients treated with methylprednisolone tended to have a shorter length of ICU stay (median (interquartile range) 6 (4 - 10), 4 (2 - 8) and 5 (2 - 8) days; p=0.015) and fewer episodes of nosocomial sepsis (47.7%, 32.6% and 48.1%; p=0.01). Conclusions. Hydrocortisone or methylprednisolone can be given as an alternative to dexamethasone in the management of critical COVID-19, and this is a feasible alternative, especially in resource-constrained settings.

Bacterial infection, antibiotic use and COVID-19: Lessons from the intensive care unit.

BACKGROUND: Empirical broad-spectrum antibiotics are frequently prescribed to patients with severe COVID-19, motivated by concern about bacterial coinfection. There is no evidence of benefit from such a strategy, while the dangers of inappropriate antibiotics are well described. OBJECTIVES: To investigate the frequency, profile and related outcomes of infections by bacterial pathogens in patients admitted to an intensive care unit (ICU) with severe COVID-19 pneumonia. METHODS: This was a prospective, descriptive study in a dedicated COVID-19 ICU in Cape Town, South Africa, involving all adult patients admitted to the ICU with confirmed COVID-19 pneumonia between 26 March and 31 August 2020. We collected data on patient comorbidities, laboratory results, antibiotic treatment, duration of admission and in-hospital outcome. RESULTS: We included 363 patients, who collectively had 1 199 blood cultures, 308 tracheal aspirates and 317 urine cultures performed. We found positive cultures for pathogens in 20 patients (5.5%) within the first 48 hours of ICU admission, while 73 additional patients (20.1%) had positive cultures later during their stay. The most frequently isolated pathogens at all sites were Acinetobacter baumannii (n=54), Klebsiella species (n=13) and coagulase-negative staphylococci (n=9). Length of ICU stay (p<0.001) and intubation (p<0.001) were associated with positive cultures on multivariate analysis. Disease severity (p=0.5), early antibiotic use (p=0.5), diabetes mellitus (p=0.1) and HIV (p=0.9) were not associated with positive cultures. Positive cultures, particularly for tracheal aspirates (p<0.05), were associated with longer ICU length of stay and mortality. Early empirical antibiotic use was not associated with mortality (odds ratio 2.5; 95% confidence interval 0.95 - 6.81). CONCLUSIONS: Bacterial coinfection was uncommon in patients at the time of admission to the ICU with severe COVID-19. Avoiding early empirical antibiotic therapy is therefore reasonable. Strategies to avoid coinfection and outbreaks in hospital, such as infection prevention and control, as well as the strict use of personal protective equipment, are important to improve outcomes.

High HIV prevalence in an early cohort of hospital admissions with COVID-19 in Cape Town, South Africa.

BACKGROUND: South Africa (SA) has a high prevalence of HIV and tuberculosis. Cape Town was the SA metropole most affected in the early stages of the COVID-19 pandemic. Early observational data from Africa may provide valuable insight into what can be expected as the pandemic expands across the continent. OBJECTIVES: To describe the prevalence, clinical features, comorbidities and outcome of an early cohort of HIV-positive and HIV-negative patients admitted with COVID-19. METHODS: This was a descriptive observational study of an early cohort of adults with COVID-19 pneumonia admitted from 25 March to 11 May 2020. RESULTS: Of 116 patients (mean age 48 years, 61% female) admitted, 24 were HIV-positive (21%). The most common symptoms reported were cough (n=88; 73%), shortness of breath (n=78; 69%), fever (n=67; 59%), myalgia (n=29; 25%) and chest pain (n=22; 20%). The most common comorbidities were hypertension (n=46; 41%), diabetes mellitus (n=43; 38%), obesity (n=32; 28%) and HIV (n=24; 21%). Mortality was associated with older age (mean (standard deviation) 55 (12) years v. 46 (14) years; p<0.01); the presence of hypertension or hypertension along with diabetes and/or obesity; lower partial pressure of arterial oxygen to fraction of inspired oxygen ratio; and higher urea level, white cell count, neutrophil count, and C-reactive protein, lactate dehydrogenase and ferritin levels, and high neutrophil to lymphocyte ratio. The overall survival rate for all hospital admissions was 86/116 (73%). In this early cohort, survival was similar in patients with HIV (n=18; 75%) compared with those without HIV (n=67; 75%) (p=1). Of the 74 patients admitted to the wards, 63 (85%) survived, whereas 22 of 42 (52%) admitted to the intensive care unit survived. CONCLUSIONS: Patients with HIV infection represented a large proportion of all COVID-19 admissions. The presentation and outcome of patients with HIV did not differ significantly from those of patients without HIV.

High HIV prevalence in an early cohort of hospital admissions with COVID-19 in Cape Town, South Africa

Background. South Africa (SA) has a high prevalence of HIV and tuberculosis. Cape Town was the SA metropole most affected in the early stages of the COVID-19 pandemic. Early observational data from Africa may provide valuable insight into what can be expected as the pandemic expands across the continent.Objectives. To describe the prevalence, clinical features, comorbidities and outcome of an early cohort of HIV-positive and HIV-negative patients admitted with COVID-19.Methods. This was a descriptive observational study of an early cohort of adults with COVID-19 pneumonia admitted from 25 March to 11 May 2020.Results. Of 116 patients (mean age 48 years, 61% female) admitted, 24 were HIV-positive (21%). The most common symptoms reported were cough (n=88; 73%), shortness of breath (n=78; 69%), fever (n=67; 59%), myalgia (n=29; 25%) and chest pain (n=22; 20%). The most common comorbidities were hypertension (n=46; 41%), diabetes mellitus (n=43; 38%), obesity (n=32; 28%) and HIV (n=24; 21%). Mortality was associated with older age (mean (standard deviation) 55 (12) years v. 46 (14) years; p<0.01); the presence of hypertension or hypertension along with diabetes and/or obesity; lower partial pressure of arterial oxygen to fraction of inspired oxygen ratio; and higher urea level, white cell count, neutrophil count, and C-reactive protein, lactate dehydrogenase and ferritin levels, and high neutrophil to lymphocyte ratio. The overall survival rate for all hospital admissions was 86/116 (73%). In this early cohort, survival was similar in patients with HIV (n=18; 75%) compared with those without HIV (n=67; 75%) (p=1). Of the 74 patients admitted to the wards, 63 (85%) survived, whereas 22 of 42 (52%) admitted to the intensive care unit survived.Conclusions. Patients with HIV infection represented a large proportion of all COVID-19 admissions. The presentation and outcome of patients with HIV did not differ significantly from those of patients without HIV

The pharmacokinetics of enteral antituberculosis drugs in patients requiring intensive care.

BACKGROUND: There is a paucity of data on the pharmacokinetics of fixed-dose combination enteral antituberculosis treatment in critically ill patients. OBJECTIVES: To establish the pharmacokinetic profile of a fixed-dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol given according to weight via a nasogastric tube to patients admitted to an intensive care unit (ICU). METHODS: We conducted a prospective, observational study on 10 patients (mean age 32 years, 6 male) admitted to an ICU and treated for tuberculosis (TB). Serum concentrations of the drugs were determined at eight predetermined intervals over 24 hours by means of high-performance liquid chromatography. RESULTS: The therapeutic maximum plasma concentration (Cmax) for rifampicin at time to peak concentration was achieved in only 4 patients, whereas 2 did not achieve therapeutic Cmax for isoniazid. No patient reached sub-therapeutic Cmax for pyrazinamide (6 were within and 4 above therapeutic range). Three patients reached sub-therapeutic Cmax for ethambutol, and 6 patients were within and 1 above the therapeutic range. Patients with a sub-therapeutic rifampicin level had a higher mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score (p=0.03) and a lower estimated glomerular filtration rate (GFR) (p=0.03). CONCLUSIONS: A fixed-dose combination tablet, crushed and mixed with water, given according to weight via a nasogastric tube to patients with TB admitted to an ICU resulted in sub-therapeutic rifampicin plasma concentrations in the majority of patients, whereas the other drugs had a more favourable pharmacokinetic profile. Patients with a sub-therapeutic rifampicin concentration had a higher APACHE II score and a lower estimated GFR, which may contribute to suboptimal outcomes in critically ill patients. Studies in other settings have reported similar proportions of patients with 'sub-therapeutic' rifampicin concentrations.