Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a diagnostic evaluation study

ObjectivesThe diagnosis of extrapulmonary tuberculosis (EPTB) is often made on clinical suspicion alone, resulting in both under- and overdiagnosis and relatively poor outcomes. In this study, we evaluated the clinical utility of the Xpert MTB/RIF on routinely collected extrapulmonary specimens in Ethiopia.MethodsThis study was carried out at Jimma University Specialized Hospital, Southwest Ethiopia. Extrapulmonary specimens were collected from 572 patients clinically suspected of suffering from EPTB. All specimens were tested for TB by smear microscopy, culture, and Xpert MTB/RIF. The diagnostic accuracy of Xpert MTB/RIF was calculated and compared to a composite reference standard (CRS), comprising clinical and laboratory results.ResultsIn total, 572 extrapulmonary specimens (279 lymph node, 159 pleural, 80 peritoneal, 45 cerebrospinal, and nine pericardial fluids) were tested. The pooled sensitivity and specificity of Xpert MTB/RIF were calculated to be 75% (95% CI 70–80) and 98% (95% CI 97–100) respectively when compared to the CRS. The highest sensitivity was documented for lymph node specimens (90%; 95% CI 86–94), moderate sensitivity for cerebrospinal fluid (53%; 95% CI 28–79), while the sensitivity was lowest for pleural (30%; 95% CI 17–44) and peritoneal (32%; 95% CI 12–51) fluids. Xpert MTB/RIF in addition detected rifampicin resistance in 13 patients, in perfect agreement with results from the line probe assay.ConclusionsXpert MTB/RIF may be used as initial diagnostic tool for testing of lymph node specimens from patients suspected of having TB lymphadenitis. The added value of Xpert MTB/RIF to diagnose pleural or peritoneal TB is limited by its poor sensitivity.     

Risk factors for Cutibacterium acnes spinal implant-associated infection: a case–case–control study

ObjectivesThe aim was to determine the characteristics of patients who developed Cutibacterium acnes spinal implant-associated infection (SIAI) and the associated risk factors.MethodsWe conducted two parallel case–control studies comparing 59 patients with SIAI caused by C. acnes (cases 1) and 93 patients with SIAI caused by other microorganisms (cases 2) diagnosed during 2010–2015 with 302 controls who underwent spinal instrumentation without subsequent infection.ResultsLate-onset infections (median time to diagnosis, 843 days versus 23 days; p < 0.001) were more common in cases 1 than in cases 2. However, 20/59 (34%) of cases 1 occurred within the first 3 months after the index surgery. In addition, cases 1 were less likely to have fever (27%, 16/59 versus 58%, 54/93; p 0.001) or wound inflammation (39%, 23/59 versus 72%, 67/93; p < 0.001). Moreover, 24/59 (40%) of cases 1 presented with polymicrobial infections, and staphylococcal pathogens accounted for 22/24 (92%) of the co-infections. By comparing and contrasting the two multivariate risk models (cases 1 versus controls and cases 2 versus controls), the following factors associated with C. acnes SIAI development were identified: age <54 years (adjusted odds ratio (aOR) 2.43, 95% confidence interval (CI) 1.09–5.58, p 0.03), a body mass index <22 kg/m² (aOR 2.47, 95% CI 1.17–5.29, p 0.02), and thoracic instrumentation (aOR 16.1, 95% CI 7.57–37.0, p < 0.001).ConclusionsFuture therapeutic and prophylactic studies on C. acnes SIAI should focus on young, thin patients who undergo spinal instrumentation procedures involving the thoracic spine.     

Severe lower limb cellulitis: defining the epidemiology and risk factors for primary episodes in a population-based case-control study

ObjectiveTo describe the epidemiology and risk factors for primary episodes of severe lower leg cellulitis (LLC).MethodsThis was a longitudinal cohort study using state-wide data linkage of adults presenting to Western Australian (WA) hospitals with a first ever LLC from January 2002 to December 2013. The study aimed at determining risk factors, medical records from the index patient, together with comparable data from controls matched by age, sex, postcode, and month of admission.ResultsDuring the period, 36 276 patients presented with their first episode of LLC. The incidence increased by 4.7% per annum, reaching 204.8 (95% CI 198.6–211.1) per 100 000 population by December 2013. Analysis of 29 062 case-control pairs showed several conditions with lower limb pathology were independently associated with LLC, including varicose veins (AOR 2.95, 95% CI 2.50–3.48, p < 0.001), lymphoedema (AOR 2.65, 95% CI 1.71–4.10, p < 0.001), tinea pedis (AOR 3.05, 95% CI 1.45–6.42, p 0.003), and saphenous vein harvest during coronary artery bypass grafting (AOR 1.74, 95% CI 1.32–2.30, p < 0.001). Also associated with LLC was obesity (AOR 2.05, 95% CI 1.82–2.31, p < 0.001), renal disease (AOR 1.28, 95% CI 1.14–1.44, p < 0.001), rheumatologic conditions (AOR 2.12, 95% CI 1.72–2.60, p < 0.001), hemiplegia/paraplegia (AOR 1.31, 95% CI 1.13–1.52, p < 0.001), and liver disease (AOR 1.77, 95% CI 1.51–2.06, p < 0.001).ConclusionsLLC presents a major burden to the health sector and is increasing with an ageing population. Given the high rates of recurrence, long-term morbidity, and economic impact, efforts to reduce primary episodes should be incorporated into the infectious diseases and healthy ageing research agenda.     

Comparison of clinical outcomes of patients infected with KPC- and NDM-producing Enterobacterales: a retrospective cohort study

ObjectivesWe aimed to compare clinical outcomes of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and those with New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales.MethodsWe performed a retrospective cohort study of all adult patients with KPC- or NDM-producing Enterobacterales isolates in a 2700-bed tertiary referral hospital in Seoul, South Korea, between 2010 and 2019. The primary outcome was 30-day mortality after first isolation of KPC- or NDM-producing Enterobacterales. The secondary outcome was the development of infection within 30 days by the colonizing isolates, among colonized patients. We performed Cox regression analysis for 30-day mortality and competing risk analysis for development of infection.ResultsA total of 859 patients were identified during the study period; 475 (55%) had KPC and 384 (45%) had NDM. Thirty-day mortality was significantly higher in the KPC group than in the NDM group (17% (81/475) vs 9% (33/384); p < 0.001). The KPC group developed infection within 30 days from the initial colonization after first isolation more frequently than the NDM group (8% (27/353) vs. 3% (10/295); p 0.02). Multivariable analysis revealed that independent risk factors for 30-day mortality were solid cancer (adjusted hazard ratio (aHR) 2.51; 95% confidence interval (CI) 1.66–3.79; p < 0.001), solid organ transplant (aHR 0.32; 95% CI 0.17–0.61; p < 0.001), a high APACHE II score (aHR 1.11; 95% CI 1.08–1.13; p < 0.001), KPC-producing Enterobacterales (aHR 1.69; 95% CI 1.02–2.79; p 0.04), previous carbapenem use within 3 months (aHR 1.86; 95% CI 1.26–2.75; p < 0.001) and site of KPC- or NDM-producing Enterobacterales infection at the time of the first culture (p < 0.001).DiscussionOur study suggests that KPC-producing Enterobacterales is significantly associated with poorer outcomes than NDM-producing Enterobacterales.     

Predictors of progression from moderate to severe coronavirus disease 2019: a retrospective cohort

ObjectiveMost cases of coronavirus disease 2019 (COVID-19) are identified as moderate, which is defined as having a fever or dry cough and lung imaging with ground-glass opacities. The risk factors and predictors of prognosis in such cohorts remain uncertain.MethodsAll adults with COVID-19 of moderate severity diagnosed using quantitative RT-PCR and hospitalized at the Central Hospital of Wuhan, China, from 1 January to 20 March 2020 were enrolled in this retrospective study. The main outcomes were progression from moderate to severe or critical condition or death.ResultsAmong the 456 enrolled patients with moderate COVID-19, 251/456 (55.0%) had poor prognosis. Multivariate logistic regression analysis identified higher neutrophil count: lymphocyte count ratio (NLR) on admission (OR 1.032, 95% CI 1.042–1.230, p 0.004) and higher C-reactive protein (CRP) on admission (OR 3.017, 95% CI 1.941–4.690, p < 0.001) were associated with increased OR of poor prognosis. The area under the receiver operating characteristic curve (AUC) for NLR and CRP in predicting progression to critical condition was 0.77 (95% CI 0.694–0.846, p < 0.001) and 0.84 (95% CI 0.780–0.905, p < 0.001), with a cut-off value of 2.79 and 25.95 mg/L, respectively. The AUC of NLR and CRP in predicting death was 0.81 (95% CI 0.732–0.878, p < 0.001) and 0.89 (95% CI 0.825–0.946, p < 0.001), with a cut-off value of 3.19 and 33.4 mg/L, respectively.ConclusionsHigher levels of NLR and CRP at admission were associated with poor prognosis of individuals with moderate COVID-19. NLR and CRP were good predictors of progression to critical condition and death.     

Evolution of the prevalence of hepatitis C virus infection and hepatitis C virus genotype distribution in human immunodeficiency virus-infected patients in Italy between 1997 and 2015

ObjectivesTo analyse the variation of hepatitis C virus (HCV) prevalence and genotype distribution and their determinants in people living with human immunodeficiency virus (HIV) who entered care between 1997 and 2015.MethodsHIV-infected patients enrolled in ICONA who were tested for HCV antibodies (HCV-Ab) were included.ResultsOverall 3407 of 12 135 (28.1%) were HCV-Ab+; and 735 of 12 135 (6.1%) were HBsAg+. Among patients whose HCV genotype was known, the most represented were genotypes 1 and 3. The prevalence of HCV infection decreased from 49.2% (2565/5217) during 1997–2002 to 10.2% (556/5466) during 2009–2015. The frequency of genotype 1a increased from 29.0% (264/911) to 43.0% (129/300), whereas genotype 3 decreased from 38.5% (351/911) to 27.0% (81/300). Independent predictors of HCV-Ab+ status were being female (adjusted OR (AOR) 1.23, 95% CI 1.04–1.50, p = 0.01), risk category (versus injecting drug users: men who have sex with men AOR 0.01, 95% CI 0.01–0.01, p <0.001; heterosexuals AOR 0.01, 95% CI 0.01–0.01, p <0.001; other/unknown AOR 0.02, 95% CI 0.01–0.02, p <0.001), being cared for in Central Italy (versus being cared for in Northern Italy: AOR 0.85, 95% CI 0.73–0.98, p <0.001), being Italian-born (AOR 1.44, 95% CI 1.16–1.80, p = 0.001) and being enrolled in less recent calendar years (versus 1997–2002: 2009–2015 AOR 0.23, 95% CI 0.19–0.27, p <0.001; 2003–2008 AOR 0.49, 95% CI 0.41–0.61, p <0.001).ConclusionsThe prevalence of HCV infection in HIV-infected patients entering into care in Italy significantly declined in more recent calendar years. After adjusting for risk factors and calendar years, HCV co-infection was more frequent in females and in those born in Italy.     

Identifying predictors for bacterial and fungal coinfection on chest computed tomography in patients with Pneumocystis pneumonia

BackgroundPneumocystis pneumonia (PCP) is a common opportunistic infection with high mortality in individuals with decreased immunity. Pulmonary coinfections with PCP are associated with poor prognosis. The study aims to identify radiological predictors for pulmonary coinfections in patients with PCP and risk factors for mortality.MethodsThis is a retrospective, five-year study was conducted in a medical center, enrolling patients diagnosed with PCP, who received a chest computed tomography (CT) scan. The radiological findings and medical records of all participants were reviewed carefully by 2 independent doctors. Univariable and multivariable analysis was performed to identify radiological predictors for pulmonary coinfection and clinical risk factors for poor prognosis.ResultsA total of 101 participants were included, of which 39 were HIV-infected and 62 were non-HIV-infected. In multivariable analysis, radiologic predictors on chest CT for coinfection with bacteria pneumonia included lack of ground glass opacity (adjusted odds ratio [aOR], 6.33; 95% confidence interval [CI], 2.03–19.77; p = 0.001) and presence of pleural effusion (aOR, 3.74; 95% CI, 1.27–10.99; p = 0.017). Predictors for fungal pneumonia included diffuse consolidation (adjusted OR, 6.27; 95% CI, 1.72–22.86; p = 0.005) and presence of pleural effusion (adjusted OR, 5.26; 95% CI, 1.44–19.17; p = 0.012). A significantly higher in-hospital mortality was associated with older age, recent corticosteroid exposure, cytomegalovirus coinfection, and acute respiratory failure.ConclusionEarly identification of pulmonary coinfections in PCP using radiological features on the CT scans, will enable appropriate treatment which is crucial to improve the prognosis.     

SARS-CoV-2 new infections among health-care workers after the first dose of the BNT162b2 mRNA COVID-19 vaccine. A hospital-wide cohort study

ObjectivesTo evaluate the effect of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on the incidence of new SARS-CoV-2 infections in health-care workers (HCW).MethodsThe evolution of the incident rate of microbiologically confirmed SARS-CoV-2 infection in a cohort of 2590 HCW after BNT162b2 mRNA SARS-CoV-2 vaccination, compared with the rate in the community (n = 170 513) was evaluated by mixed Poisson regression models.ResultsA total of 1820 HCW (70.3% of total) received the first dose of the BNT162b2 mRNA vaccine between 10 January and 16 January 2021, and 296 (11.4%) received it the following week. All of them completed vaccination 3 weeks later. Incidence rates of SARS-CoV-2 infection after the first dose of mRNA SARS-CoV-2 vaccine declined by 71% (Incidence Rate Ratio (IRR) 0.286, 95% CI 0.174–0.468; p < 0.001) and by 97% (IRR 0.03, 95% CI 0.013–0.068; p < 0.001) after the second dose, compared with the perivaccine time. SARS-CoV-2 incidence rates in the community (with a negligible vaccination rate) had a much lower decline: 2% (IRR 0.984, 95% CI 0.943–1.028; p 0.47) and 61% (IRR 0.390, 95% CI 0.375–0.406; p < 0.001) for equivalent periods. Adjusting for the decline in the community, the reduction in the incident rates among HCW were 73% (IRR 0.272, 95% CI 0.164–0.451 p < 0.001) after the first dose of the vaccine and 92% (IRR 0.176, 95% CI 0.033–0.174; p < 0.001) after the second dose.ConclusionsmRNA SARS-CoV-2 vaccination is associated with a dramatic decline in new SARS-CoV-2 infection among HCW, even before the administration of the second dose of the vaccine.     

Usefulness of EQUAL Candida Score for predicting outcomes in patients with candidaemia: a retrospective cohort study

BackgroundThe European Confederation of Medical Mycology (ECMM) Quality of Clinical Candidaemia Management (EQUAL) score is a tool designed by the ECMM to measure guideline adherence. The current study investigated the association between EQUAL scores and clinical outcomes.MethodsThis retrospective study was conducted in three hospitals in Taiwan. Patients with candidaemia between January 2014 and July 2018 were enrolled. Guideline adherence was evaluated using EQUAL score indicators. Clinical outcomes and predictors of 30-day mortality were investigated.ResultsA total of 384 patients were enrolled. The overall mean EQUAL score was 8.91 ± 3.42 (9.42 ± 3.60 in survivors vs. 8.10 ± 2.94 in non-survivors, p < 0.001). Higher scores were positively correlated with survival (p < 0.001). Scores of 16–22 indicated the highest survival rates (p for trend <0.001). The Kaplan–Meier plot revealed that patients with EQUAL scores ≥10 exhibited significantly higher survival rates (p < 0.001) than those with scores <10. Multivariable analysis revealed that EQUAL scores ≥10 (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.19–0.74), advanced age (OR 1.02, 95% CI 1.00–1.04), septic shock (OR 4.42, 95% CI 2.09–9.36), high sequential organ failure assessment scores (OR 4.28, 95% CI 2.15–8.52), intravascular catheter-related source (OR 0.42, 95% CI 0.19–0.94) and central venous catheter retention (OR 5.41, 95% CI 2.06–14.24) were independent predictors of 30-day mortality.DiscussionGreater guideline adherence with a higher EQUAL score was significantly associated with survival. An EQUAL score cutoff point <10 predicted 30-day mortality.     

A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients

ObjectivesTo describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance.MethodsCirrhotic patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model.ResultsWe enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure–SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29–18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93–5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28–1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73–4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48–4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12–0.73; p 0.008).ConclusionsMDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.     

Predictors of poor prognosis in healthy,young, individuals with SARS-CoV-2 infections

ObjectivesTo identify predictors of poor prognosis in previously healthy young individuals admitted to hospital with coronavirus disease 2019 (COVID-19).MethodsWe studied a cohort of patients hospitalized with COVID-19. All patients without co-morbidities, without usual treatments and ≤65 years old were selected from an international registry (HOPE-COVID-19, NCT04334291). We focused on baseline variables—symptoms and signs at admission—to analyse risk factors for poor prognosis. The primary end point was a composite of major adverse clinical events during hospitalization including mortality, mechanical ventilation, high-flow nasal oxygen therapy, prone, sepsis, systemic inflammatory response syndrome and embolic events.ResultsOverall, 773 healthy young patients were included. The primary composite end point was observed in 29% (225/773) and the overall mortality rate was 3.6% (28/773). In the combined event group, 75% (168/225) of patients were men and the mean age was 49 (±11) years, whereas in the non-combined event group, the prevalence of male gender was 43% (238/548) and the mean age was 42 (±13) years (p < 0.001 for both). On admission, respiratory insufficiency and cough were described in 51.4% (114/222) and 76% (170/223) of patients, respectively, in the combined event group, versus 7.9% (42/533) and 56% (302/543) of patients in the other group (p < 0.001 for both). The strongest independent predictor for the combined end point was desaturation (Spo₂ <92%) (OR 5.40; 95% CI 3.34–8.75; p < 0.001), followed by tachypnoea (OR 3.17; 95% CI 1.93–5.21; p < 0.001), male gender (OR 3.01; 95% CI 1.96–4.61; p < 0.001) and pulmonary infiltrates on chest X-ray at admission (OR 2.21; 95% CI 1.18–4.16; p 0.014).ConclusionsMajor adverse clinical events were unexpectedly high considering the baseline characteristics of the cohort. Signs of respiratory compromise at admission and male gender, were predictive for poor prognosis among young healthy patients hospitalized with COVID-19.     

Community-acquired pneumonia in patients with bacterial meningitis: a prospective nationwide cohort study

ObjectivePneumonia is considered a focus of infection in patients presenting with community-acquired bacterial meningitis but the impact on disease course is unclear. The aim was to study presenting characteristics, clinical course and outcome of meningitis patients with co-existing pneumonia on admission.MethodsWe evaluated adult patients with community-acquired bacterial meningitis with pneumonia on admission in a nationwide, prospective cohort performed from March 2006 to June 2017. We performed logistic regression analysis to identify clinical characteristics predictive of pneumonia on admission, and to quantify the effect of pneumonia on outcome.ResultsPneumonia was diagnosed on admission in 315 of 1852 (17%) bacterial meningitis episodes and confirmed by chest X-ray in 256 of 308 (83%) episodes. Streptococcus pneumoniae was the causative organism in 256 of 315 episodes (81%). Pneumonia on admission was associated with advanced age (OR 1.03 per year increase, 95% CI 1.02–1.04, p < 0.001), alcoholism (OR 1.96, 95% CI 1.23–3.14, p 0.004), cancer (OR 1.54, 95% CI 1.12–2.13, p 0.008), absence of otitis or sinusitis (OR 0.44, 95% CI 0.32–0.59, p < 0.001) and S. pneumoniae (OR 2.14, 95% CI 1.55–2.95, p < 0.001) in the multivariate analysis. An unfavourable outcome defined as a score of 1–4 on the Glasgow Outcome Scale was observed in 172 (55%) episodes and 87 patients (28%) died. Pneumonia on admission was independently associated with unfavourable outcome and mortality in the multivariate analysis (OR 1.48, 95% CI 1.12–1.96; p 0.005).ConclusionPneumonia on admission in bacterial meningitis is a frequent coexisting infection and is independently associated with unfavourable outcome and mortality.     

Risk factors for candidaemia in hospitalized patients with liver cirrhosis: a multicentre case–control–control study

ObjectivesThe aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis.MethodsThis was a case–control–control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission.ResultsDuring the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09–4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19–4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00–7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26–6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62–9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11–10.18), p <0.001] Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19–0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97–2.75) p = 0.06).ConclusionsWe identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor.     

Evaluating the risk of hyperkalaemia and acute kidney injury with cotrimoxazole: a retrospective observational study

ObjectivesIncreasing antimicrobial resistance has renewed interest in older, less used antimicrobials. Cotrimoxazole shows promise; however, hyperkalaemia and acute kidney injury (AKI) are potential complications. Identifying risk factors for and quantification of these events is required for safe use. This study aimed to evaluate predictors of cotrimoxazole-associated AKI and hyperkalaemia in a clinical setting.MethodsPatients prescribed cotrimoxazole were identified using electronic healthcare records over 3 years (1 April 2016 to 31 March 2019). Individual risk factors were recognized. Serum creatinine and potassium trends were analysed over the subsequent 21 days. AKI and patients with hyperkalaemia were classified using Kidney Disease Improving Global Outcomes (KDIGO) and laboratory criteria. Univariate and multiple logistic regression analyses were performed.ResultsAmong 214 patients prescribed cotrimoxazole, 42 (19.6%, 95% confidence interval (CI) 14.6–25.7) met AKI criteria and 33 (15.4%, 95% CI 11.0–21.1) developed hyperkalaemia. Low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m², odds ratio (OR) 7.78, 95% CI 3.57–16.13, p < 0.0001) and cardiac disorders (OR 2.40, 95% CI 1.17–4.82, p 0.011) predicted AKI, while low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m², OR 6.80, 95% CI 3.09–15.06, p < 0.0001) and higher baseline serum potassium (p 0.001) predicted hyperkalaemia. Low-dose cotrimoxazole (<1920 mg/d) was associated with lower AKI and hyperkalaemia risk (p 0.007 and 0.019 respectively). Early (within the first 2–4 days of therapy) serum creatinine changes predicted AKI (OR 3.65, 95% CI 1.73–7.41, p 0.001), and early serum potassium changes predicted hyperkalaemia (>0.6 mmol/L, OR 2.47, 95% CI 1.14–5.27, p 0.0236).ConclusionsCotrimoxazole-associated AKI and hyperkalaemia is frequent and dose dependent. Renal function, serum potassium and preexisting cardiac disorders should be evaluated before prescribing cotrimoxazole. Serum creatinine and potassium monitoring within first 2 to 4 days of treatment to identify susceptible patients is recommended, and the lowest effective dose ought to be prescribed.     

Patient pathway analysis of tuberculosis diagnostic delay: a multicentre retrospective cohort study in China

ObjectivesDelay in diagnosis of tuberculosis (TB) is an important but under-appreciated problem. Our study aimed to analyse the patient pathway and possible risk factors of long diagnostic delay (LDD).MethodsWe enrolled 400 new bacteriologically diagnosed patients with pulmonary TB from 20 hospitals across China. LDD was defined as an interval between the initial care visit and the confirmation of diagnosis exceeding 14 days. Its potential risk factors were investigated by multivariate logistic regression and multilevel logistic regression. Hospitals in China were classified by increasing size, from level 0 to level 3. TB laboratory equipment in hospitals was also evaluated.ResultsThe median diagnostic delay was 20 days (IQR: 7–72 days), and 229 of 400 patients (57.3%, 95%CI 52.4–62.1) had LDD; 15% of participants were diagnosed at the initial care visit. Compared to level 0 facilities, choosing level 2 (OR 0.27, 95%CI 0.12–0.62, p 0.002) and level 3 facilities (OR 0.34, 95%CI 0.14–0.84, p 0.019) for the initial care visit was independently associated with shorter LDD. Equipping with smear, culture, and Xpert at initial care visit simultaneously also helped to avoid LDD (OR 0.28, 95%CI 0.09–0.82, p 0.020). The multilevel logistic regression yielded similar results. Availability of smear, culture, and Xpert was lower in level 0–1 facilities than in level 2–3 facilities (p < 0.001, respectively).ConclusionsMost patients failed to be diagnosed at the initial care visit. Patients who went to low-level facilities initially had a higher risk of LDD. Improvement of TB laboratory equipment, especially at low-level facilities, is urgently needed.     

N-antigenemia detection by a rapid lateral flow test predicts 90-day mortality in COVID-19: A prospective cohort study

ObjectivesTo evaluate if the detection of N antigen of SARS-CoV-2 in plasma by a rapid lateral flow test predicts 90-day mortality in COVID-19 patients hospitalized at the wards.MethodsThe presence of N-antigenemia was evaluated in the first 36 hours after hospitalization in 600 unvaccinated COVID-19 patients, by using the Panbio COVID-19 Ag Rapid Test Device from Abbott (Abbott Laboratories Inc., Chicago, IL, USA). The impact of N-antigenemia on 90-day mortality was assessed by multivariable Cox regression analysis.ResultsPrevalence of N-antigenemia at hospitalization was higher in nonsurvivors (69% (82/118) vs. 52% (250/482); p < 0.001). The patients with N-antigenemia showed more frequently RNAemia (45.7% (148/324) vs. 19.8% (51/257); p < 0.001), absence of anti-SARS-CoV-2 N antibodies (80.7% (264/327) vs. 26.6% (69/259); p < 0.001) and absence of S1 antibodies (73.4% (240/327) vs. 23.6% (61/259); p < 0.001). The patients with antigenemia showed more frequently acute respiratory distress syndrome (30.1% (100/332) vs. 18.7% (50/268); p = 0.001) and nosocomial infections (13.6% (45/331) vs. 7.9% (21/267); p = 0.026). N-antigenemia was a risk factor for increased 90-day mortality in the multivariable analysis (HR, 1.99 (95% CI,1.09–3.61), whereas the presence of anti-SARS-CoV-2 N-antibodies represented a protective factor (HR, 0.47 (95% CI, 0.26–0.85).DiscussionThe presence of N-antigenemia or the absence of anti-SARS-CoV-2 N-antibodies after hospitalization is associated to increased 90-day mortality in unvaccinated COVID-19 patients. Detection of N-antigenemia by using lateral flow tests is a quick, widely available tool that could contribute to early identify those COVID-19 patients at risk of deterioration.     

Recurrent pulmonary tuberculosis after treatment success: a population-based retrospective study in China

ObjectivesPost-treatment recurrence remains a challenge for the global control of tuberculosis (TB). This study investigated longitudinal data on pulmonary TB recurrence rates and risk factors for recurrence among successfully treated smear-positive tuberculosis cases in China.MethodsBetween 1st January 2009 and 31st December 2016 we evaluated 33 441 treatment-naïve patients diagnosed with sputum-smear-positive, non-multidrug-resistant TB in Hangzhou, China. We included the data of 9828 patients with TB who were treated successfully.ResultsA total of 4.9% of the cases were recurrent (479/9828), identified within a median observation period lasting 1565 days. Altogether, 51.1% (245/479) of the recurrences occurred within 1 year. The cumulative 2- and 5-year recurrence rates were 3.90% (95% confidence interval (CI) 3.3–4.5%) and 5.4% (95%CI 4.8–6.0%), respectively. Prolonged treatment (over 7 months) occurred in 64.7% (6363/9828), with a median treatment duration of 242 days (interquartile range 195–348 days). Male sex (adjusted hazard ratio (aHR) (95%CI) 1.61 (1.30–2.00), p < 0.001), age 60 years old or older (aHR (95%CI) 2.03 (1.70–2.44), p < 0.001), pulmonary cavity (aHR (95%CI) 1.51 (1.25–1.82), p < 0.001) and sputum positivity at 2 months (aHR (95%CI) 1.39 (1.05–1.81), p 0.02) all increased the risk of TB recurrence. Prolonged treatment was associated with reduced TB recurrence (aHR (95%CI) 0.73 (0.61–0.88), p 0.001).ConclusionsRecurrence remains a problem for successfully treated patients with sputum-smear-positive pulmonary TB, especially those with independent risk factors. Further analysis of prolonged treatment is required.     

A novel PCR-based point-of-care method facilitates rapid,efficient, and sensitive diagnosis of influenza virus infection

ObjectiveThe aim of this single-centre study was the comparative analysis of the GeneXpert (Cepheid Inc.) and the LIAT (Roche) system for the rapid polymerase chain reaction (PCR)-based detection of influenza A (IA) and influenza B (IB) viruses.Patients and methodsDuring the 2017–2018 flu season, 651 prospectively collected samples (throat and nasal swabs) of patients with symptoms of influenza-like illness or acute respiratory infection were tested for the presence of IA and IB viruses using the GeneXpert and LIAT systems. To evaluate the usefulness for near-patient testing, a LIAT system was installed at the Department of Emergency Medicine, and sample testing was performed on site. Reference testing of all samples was performed with the Xpert Flu assay and for 313 samples in addition with the Xpert Xpress Flu/RSV (respiratory syncytial virus) assay at the central laboratory. Analysis of all samples was carried out within 24 hr after collection.ResultsOverall, 267 of the 651 samples analysed were positive for influenza viruses in at least one of the three assays investigated (IA, 88; IB, 179). The overall rates of agreement between the LIAT assay and the Xpert Flu assay was 96.0% for the detection of IA and IB viruses. The sensitivity and specificity of the LIAT assay compared to the Xpert Flu assay for the detection of IA was 98.80% (95% confidence interval (CI) 93.47–99.97%) and 99.12% (95% CI, 97.96% to 99.71%) and for the detection of IB 98.76% (95% CI 95.58–99.85%), and 96.33% (95% CI 94.26–97.81%), respectively. The LIAT assay showed a statistically significant higher detection rate of IB virus than the Xpert Flu assay (p <0.01). No significant difference was found between the detection rate of the LIAT assay and the Xpert Xpress Flu/RSV assay. The mean time to the availability of a definite test result was significantly shorter with the on-site LIAT system than the GeneXpert system (mean 59 min saving time; p <0.01).ConclusionThe LIAT system represents a robust and highly sensitive point-of-care device for the rapid PCR-based detection of influenza A and influenza B viruses.     

Diagnostic Accuracy of Xpert MTB/RIF for Extrapulmonary Tuberculosis Specimens: Establishing a Laboratory Testing Algorithm for South Africa

South Africa implemented Xpert MTB/RIF as the initial diagnostic test for pulmonary tuberculosis (TB). Xpert MTB/RIF''s accuracy for diagnosing extrapulmonary tuberculosis (EPTB) was investigated. EPTB specimens (n = 7,916) from hospitalized patients received over a 6-month period at a high-throughput TB referral laboratory in Johannesburg were investigated. Large-volume specimens were centrifuged, tissue biopsy specimens homogenized, and all specimens checked for growth of contaminating bacteria on blood agar. Contaminated samples received NALC-NaOH (N-acetyl-l-cysteine–sodium hydroxide) decontamination prior to liquid culture. Residual specimens (volumes > 1 ml) after inoculation of culture (n = 1,175) were tested using the Xpert MTB/RIF sputum protocol. Using culture as the reference, Xpert MTB/RIF''s overall sensitivity was 59% (95% confidence interval [95% CI], 53% to 65%) and specificity was 92% (CI, 90% to 94%), with the highest sensitivities of 91% (95% CI, 78% to 97%) for pus, 80% (95% CI, 56% to 94%) for lymph node aspirates, and 51% (95% CI, 44% to 58%) for fluids (ascitic, 59%; pleural, 47%). A difference in sensitivities was noticed between specimens classified as having a thick (87% [95% CI, 76% to 94%]) versus clear (watery) (48% [95% CI, 36% to 61%]) appearance. This was unchanged with traces of blood (52% [95% CI, 44% to 60%]) or precentrifugation (57% [95% CI, 28% to 82%]) among clear specimens. Xpert MTB/RIF generated an additional 124 specimen results that were contaminated by Mycobacterial Growth Indicator Tubes (MGIT; 10.5%) and diagnosed rifampin (RIF) resistance earlier (9.6% [25/260]). Xpert MTB/RIF''s performance on EPTB specimens provides very promising results and should be considered for incorporation into national TB guidelines. Xpert MTB/RIF is less affected by contaminating bacteria and reduces laboratory labor and diagnostic delay compared to traditional methods.     

Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study

ObjectivesWe aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity.MethodsThis was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2–4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity.ResultsOf 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2–4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5–163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m², 95% confidence interval (CI) 1.014–1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782–3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015–1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146–3.443, p 0.014). No serious adverse events resulting from the vaccine were reported.ConclusionsKidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.