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ABSTRACTBackgroundRickettsia felis is emergent in tropical areas. Despite its high morbidity, its natural history has not yet been fully determined. We investigated the role of the common household booklouse, Liposcelis bostrychophila, recently found to harbour R. felis.MethodsBlood samples from 372 febrile patients from Senegalese villages, as well as nasal and skin samples from 264 asymptomatic individuals, were tested for cat flea-associated and booklice-associated strains of R. felis. Dust samples from beds were collected to isolate booklice and R. felis. Mice were infected with aerosol of R. felis strain from naturally infected booklice.ResultsForty febrile patients (11%) were infected by R. felis, including 26 (7%) by the booklice-associated strain. Nine nasal samples (3.4%) and 28 skin samples (10.6%) contained R. felis, including seven and 24, respectively, with the booklice-associated strain. The presence of live L. bostrychophila was observed in 32 dust samples (16.8%); R. felis was identified in 62 dust samples (32.5%). Several mice samples were positive for R. felis; interstitial lymphohistiocytic infiltrates were identified in lungs.ConclusionsL. bostrychophila may be a reservoir of R. felis. The booklice-associated strain is pathogenic in mammals causing pneumonia. Human infection may be acquired via inhalation of infected booklice particles.

by Olena V. Moshynets, Taras P. Baranovskyi, Scott Cameron, Olga S. Iungin, Ianina Pokholenko, Robyn Jerdan, Aleksandr Kamyshnyi, Alexey A. Krikunov, Viktoria V. Potochilova, Kateryna L. Rudnieva, Andrew J. Spiers

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which combination will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays.

by Mansoor Saleh, Karishma Sharma, Jasmit Shah, Farrok Karsan, Angela Waweru, Martin Musumbi, Reena Shah, Shahin Sayed, Innocent Abayo, Noureen Karimi, Stacey Gondi, Sehrish Rupani, Grace Kirathe, Heldah Amariati

Background Low dose radiation therapy (LDRT) has been used for non-malignant conditions since early 1900s based on the ability of single fractions between 50–150 cGy to inhibit cellular proliferation. Given scarcity of resources, poor access to vaccines and medical therapies within low and middle income countries, there is an urgent need to identify other cost-effective alternatives in management of COVID-19 pneumonia. We conducted a pilot phase Ib/II investigator-initiated clinical trial to assess the safety, feasibility, and toxicity of LDRT in patients with severe COVID-19 pneumonia at the Aga Khan University Hospital in Nairobi, Kenya. Additionally, we also assessed clinical benefit in terms of improvement in oxygenation at day 3 following LDRT and the ability to avoid mechanical ventilation at day 7 post LDRT. Methods Patients with both polymerase chain reaction (PCR) and high-resolution computer tomogram (HRCT) confirmed severe COVID-19 pneumonia, not improving on conventional therapy including Dexamethasone and with increasing oxygen requirement were enrolled in the study. Patients on mechanical ventilation were excluded. Eligible patients received a single 100cGy fraction to the whole lung. In the absence of any dose limiting toxicity the study proposed to treat a total of 10 patients. The primary endpoints were to assess the safety/feasibility, and toxicity within the first 24 hours post LDRT. The secondary endpoints were to assess efficacy of LDRT at Day 3, 7, 14 and 28 post LDRT. Results Ten patients were treated with LDRT. All (100%) of patients were able to complete LDRT without treatment related SAE within the first 24 hours post treatment. None of the patients treated with LDRT experienced any acute toxicity as defined by change in clinical and respiratory status at 24hr following LDRT. Majority (90%) of patients avoided mechanical ventilation within 7 days of LDRT. Four patients (40%) demonstrated at least 25% improvement in oxygen requirements within 3 days. Six patients (60%) were discharged and remained off oxygen, whereas four progressed and died (1 due to sepsis and 3 in cytokine storm). Median time to discharge (n = 6) was 16.5 days and median time to death (n = 4) was 11.0 days. Patients who ultimately died showed elevated inflammatory markers including Ferritin, CRP and D-dimers as compared to those who were discharged alive. Conclusion LDRT was feasible, safe and shows promise in the management of severe COVID-19 pneumonia including in patients progressing on conventional systemic treatment. Additional phase II trials are warranted to identify patients most likely to benefit from LDRT.…

by Hakjun Hyun, Joon Young Song, Jin Gu Yoon, Hye Seong, Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim

Background Healthcare-associated pneumonia (HCAP) lies in the intersection of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). Although HCAP is excluded from the revised HAP guideline, reassessment for HCAP is needed considering its heterogeneous characteristics. Methods The microbiological distribution, antibiotic resistance, and clinical outcomes in CAP, HCAP, and HAP were studied retrospectively. The susceptibility to standard CAP regimens (β-lactams plus macrolide or fluoroquinolone monotherapy) and rates of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) infections were evaluated in the CAP group and HCAP subgroups. Results In total, 933 cases were included (CAP, n = 557; HCAP, n = 264; HAP, n = 112). In the CAP and HCAP cases, Streptococcus pneumoniae (7.4% vs. 5.7%) and P. aeruginosa (9.2% vs. 18.6%) were the most common gram-positive and gram-negative pathogens. Staphylococcus aureus (methicillin-resistant, 2.7%; methicillin-susceptible, 2.4%) and carbapenem-resistant Acinetobacter baumannii (20.5%) were the most common Gram-positive and Gram-negative pathogens in the HAP group, respectively. Higher susceptibility to levofloxacin was observed in CAP and HCAP isolates than that to β-lactam agents. However, levofloxacin non-susceptibility was significantly higher in long-term care facility (LTCF)-onset HCAP compared to community-onset HCAP (43.6% vs. 22.7%, P = 0.014). Conclusion HCAP showed higher rates of P. aeruginosa and MRSA infections than CAP. Empirical antipseudomonal therapy should be considered in the treatment of HCAP. Prior isolation of P. aeruginosa was the most important risk factor for P. aeruginosa infection.…

Abstract

Background

Antimicrobial resistance is a major threat to global health and the world economy. The economic burden of carbapenem-resistant infections has not previously been evaluated. We aimed to compare the potential economic burden and clinical outcomes between carbapenem-resistant infections and carbapenem-susceptible infections in Japan.

Methods

We conducted a retrospective cohort study using electronic medical records. Patients aged 15 years or older and with the diagnosis of pneumonia, urinary tract infection, biliary infection, and sepsis were included. Multivariable regression models with random effects were used to estimate the impact of carbapenem resistance on cost, length of hospital stay, and in-hospital mortality.

Results

Among the 9,517 patients, 86 (0.9%) had carbapenem-resistant (CR) infections. Compared to carbapenem-susceptible (CS) infections, the patients with the CR infections were significantly more likely to receive mechanical ventilation (37.2 vs. 21.2%, P-value = 0.003), antibiotics (88.4 vs. 63.0%, P-value < 0.001), and especially carbapenem (31.4 vs. 8.3%, P-value < 0.001), before the bacterial culture test positive. Significantly higher median costs were found for the CR infections than the CS infections in the categories of medications (3477 US dollars vs. 1609 US dollars), laboratory tests (2498 US dollars, vs. 1845 US dollars), and hospital stay (14,307 US dollars vs. 10,560 US dollars). In the multivariable regression analysis, the length of stay was 42.1% longer and the cost was 50.4% higher in the CR infections than in the CS infections. The risk of in-hospital mortality did not differ between the two groups (odds ratio 1.24, 95% CI 0.72–2.11), due to the small sample size. The result was robust with a similar trend in the analysis using the inverse probability treatment weighting method.

Conclusions

Compared to carbapenem-susceptible infections, carbapenem-resistant infections were associated with a higher cost and a longer length of stay. Detailed cost analysis showed significant differences in the categories of medication, laboratory tests, and hospital stay. To our knowledge, this study is the first to assess the potential economic burden of carbapenem-resistant infections using a large hospital-based database.

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Objective

To compare the patient profile and outcomes in Qatar during the first and second waves of the COVID-19 pandemic.

Setting

A retrospective observational study was conducted comparing the demographic, clinical and laboratory characteristics of patients with COVID-19 infection admitted to a secondary care hospital, during the first and second waves of the pandemic.

Participants

1039 patients from the first wave and 991 from the second wave who had pneumonia on chest X-ray and had a confirmed SARS-CoV-2 infection by a real-time PCR test of a nasopharyngeal swab were included. Patients with a normal chest X-ray and those who had a negative PCR test despite a positive COVID-19 antigen test were excluded.

Outcome

Length of stay, need for mechanical ventilation, final disposition and mortality were the key outcomes studied

Results

Influenza like symptoms (18.5% in the first wave vs 36.1% in the second wave, p 0.001), cough (79.2% vs 87%, p<0.001) and dyspnoea (27.5% vs 38% p<0.001) were more common in the second wave. Second wave patients had significantly higher respiratory rate, lower peripheral oxygen saturation, needed more supplemental oxygen and had higher incidence of pulmonary embolism. More patients received hydroxychloroquine and antibiotics during the first wave and more received steroids, antivirals and interleukin-1 antagonist during the second wave. The second wave had a shorter length of stay (14.58±7.75 vs 12.61±6.16, p<0.001) and more patients were discharged home (22% vs 10%, p<0.001).

Conclusions

Patients who presented during the second wave of COVID-19 pandemic appeared to be more ill clinically and based on their laboratory parameters. They required shorter hospitalisation and were more likely to be discharged home. This could represent greater expertise in handling such patients that was acquired during the first wave as well as use of more appropriate and combination therapies during the second wave.

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John Bunyan coined the phrase “The Captain of all these the men of death” and applied it to consumption (ie, tuberculosis); Sir William Osler subsequently applied the phrase (“Captain of the men of death”) to pneumonia in the pre-antibiotic era; but both diseases gave way to tobacco-related lung disease, which now has the unanswerable claim on that title. Eventually, the pioneering work of Sir Richard Doll and many others was recognised, demonstrating the toll of premature death caused by the tobacco industry, but only after many decades of harm.

Abstract

Background

Pneumocystis jirovecii pneumonia (PJP) in an immunocompromised host is often associated with the Macklin effect, which can progress to spontaneous pneumomediastinum (SPM), subcutaneous emphysema (SCE), and pneumothorax (PNX). Diagnosing the causative organism of these conditions in non-HIV infected patients and treating hypoxemia while preventing further lung damage can be challenging. This study examines the case of a non-HIV infected male with SPM, SCE, and PNX secondary to severe Pneumocystis jirovecii (PJ) infection.

Case presentation

A 53-year-old male with pure red cell aplasia (PRCA) was admitted with fever, dry cough, and shortness of breath. His respiratory function progressively deteriorated due to the development of SPM, SCE, and PNX, eventually requiring endotracheal intubation and invasive ventilation. As a result of high pressure in his airways occasioned by lung recruitment maneuvers, his pulmonary parameters worsened, necessitating veno-venous (VV) extracorporeal membrane oxygenation (ECMO) therapy. The early initiation of VV-ECMO facilitated ultra-protective lung ventilation and prevented the progression of SPM, SCE, and PNX. Traditional diagnostic assays were unrevealing, whereupon the patient resorted to the metagenomic next-generation sequencing technology for uncovering potential pathogens. Consequently, we detected a significantly higher infection by PJ in the patient’s bronchoscopy lavage fluid. Finally, the patient was successfully treated with appropriate antimicrobials and was decannulated after nine days of ECMO support.

Conclusions

SPM, SCE, and PNX are rare clinical manifestations of PJP. However, they can be considered as poor prognostic factors of the infection. Physicians should, therefore, be alert to the possibility of PJP in immunocompromised patients.

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Abstract

Background

There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB).

Methods

We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed.

Results

PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02–1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12–1.72, p = 0.003) and being “overweight or obese” (AHR 1.30 95%CI 1.03–1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95–1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84–2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels.

Conclusion

In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population.

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Introduction

Community-acquired pneumonia (CAP), frequently encountered in both outpatient and inpatient settings, is the leading cause of infectious disease-related mortality. While equipoise regarding the optimal duration of antimicrobial therapy to treat CAP remains, recent studies suggest shorter durations of therapy may achieve optimal outcomes. We have therefore planned a systematic review and meta-analysis evaluating the impact of shorter versus longer durations of antibiotic therapy for patients with CAP.

Methods and analysis

We searched Ovid MEDLINE, Embase, CINAHL and Cochrane Central Register of Controlled Trials from inception to September 2021 for randomised controlled trials evaluating shorter versus longer duration of antibiotics. Eligible studies will compare durations with a minimum difference of two days of antibiotic therapy, irrespective of antibiotic agent, class, route, frequency or dosage, and will report on any patient-important outcome of benefit or harm. Paired reviewers working independently will conduct title and abstract screening, full-text screening, data extraction and risk of bias (RoB) evaluation using a modified Cochrane RoB 2.0 tool. We will perform random-effects modelling for meta-analyses, with study weights generated using the inverse variance method, and will assess certainty in effect estimates using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN) tool will inform assessments of credibility of subgroup effects based on severity of illness, drug class, duration of therapy, setting of CAP acquisition and RoB.

Ethics and dissemination

The results will be of importance to general practitioners and internists managing CAP, and may directly inform international clinical guidance. Where concerns regarding antimicrobial resistance continue to grow internationally, this evidence summary may motivate new recommendations regarding shorter durations of therapy. We intend to disseminate our findings via national and international conferences, and publication in a peer-reviewed journal.

PROSPERO registration number

CRD42021283990.

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Christopher J L Murray and colleagues1 provide a sobering analysis on the burden of common antimicrobial-resistant infections and a warning that, as a global community, we are rapidly surrendering any advantage we had on treating infections such as pneumonia and sepsis.2…

ABSTRACTBackgroundEmpiric antibiotic use among hospitalized U.S. adults is largely undescribed. Identifying factors associated with broad-spectrum empiric therapy may inform antibiotic stewardship interventions and facilitate benchmarking.MethodsWe performed a retrospective cohort study of adults discharged in 2019 from 928 hospitals in the Premier Healthcare Database. “Empiric” Gram-negative antibiotics were defined by administration before Day 3 of hospitalization. Multivariable logistic regression models with random-effects by hospital were used to evaluate associations between patient and hospital characteristics and empiric receipt of broad-spectrum, compared to narrow-spectrum, Gram-negative antibiotics.Results2,928,657 of 8,017,740 (37%) hospitalized adults received empiric Gram-negative antibiotics. Among 1,781,306 who received broad-spectrum therapy, 30% did not have a common infectious syndrome present-on-admission (pneumonia, urinary tract infection, sepsis, or bacteremia), or surgery or an ICU stay in the empiric window. Holding other factors constant, males were 22% more likely (aOR 1.22, 95% CI: 1.22–1.23), and all non-White racial groups were 6%-13% less likely (aOR range: 0.87–0.94), to receive broad-spectrum therapy. There were significant prescribing differences by region, with the highest adjusted odds of broad-spectrum therapy in the U.S. West South Central. Even after model adjustment, there remained substantial inter-hospital variability: among patients receiving empiric therapy, the probability of receiving broad-spectrum antibiotics varied as much as 34 + percentage-points due solely to the admitting hospital (95% interval of probabilities: 43% - 77%).ConclusionsEmpiric Gram-negative antibiotic use is highly variable across U.S. regions, and there is high, unexplained inter-hospital variability. Sex and racial disparities in the receipt of broad-spectrum therapy warrant further investigation.

Objective

To identify aetiologies of childhood community-acquired pneumonia (CAP) based on a comprehensive diagnostic approach.

Design

‘Partnerships for Enhanced Engagement in Research-Pneumonia in Paediatrics (PEER-PePPeS)’ study was an observational prospective cohort study conducted from July 2017 to September 2019.

Setting

Government referral teaching hospitals and satellite sites in three cities in Indonesia: Semarang, Yogyakarta and Tangerang.

Participants

Hospitalised children aged 2–59 months who met the criteria for pneumonia were eligible. Children were excluded if they had been hospitalised for >24 hours; had malignancy or history of malignancy; a history of long-term (>2 months) steroid therapy, or conditions that might interfere with compliance with study procedures.

Main outcome(s) measure(s)

Causative bacterial, viral or mixed pathogen(s) for pneumonia were determined using microbiological, molecular and serological tests from routinely collected specimens (blood, sputum and nasopharyngeal swabs). We applied a previously published algorithm (PEER-PePPeS rules) to determine the causative pathogen(s).

Results

188 subjects were enrolled. Based on our algorithm, 48 (25.5%) had a bacterial infection, 31 (16.5%) had a viral infection, 76 (40.4%) had mixed bacterial and viral infections, and 33 (17.6%) were unable to be classified. The five most common causative pathogens identified were Haemophilus influenzae non-type B (N=73, 38.8%), respiratory syncytial virus (RSV) (N=51, 27.1%), Klebsiella pneumoniae (N=43, 22.9%), Streptococcus pneumoniae (N=29, 15.4%) and Influenza virus (N=25, 13.3%). RSV and influenza virus diagnoses were highly associated with Indonesia’s rainy season (November–March). The PCR assays on induced sputum (IS) specimens captured most of the pathogens identified in this study.

Conclusions

Our study found that H. influenzae non-type B and RSV were the most frequently identified pathogens causing hospitalised CAP among Indonesian children aged 2–59 months old. Our study also highlights the importance of PCR for diagnosis and by extension, appropriate use of antimicrobials.

Trail registration number

NCT03366454

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Abstract

Background

There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB).

Methods

We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed.

Results

PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02–1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12–1.72, p = 0.003) and being “overweight or obese” (AHR 1.30 95%CI 1.03–1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95–1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84–2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels.

Conclusion

In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population.

…

Abstract

Background

Melioidosis caused by Burkholderia pseudomallei is an emerging infection in Sri Lanka with a high case fatality rate. The disease usually manifests as pneumonia, however multisystem involvement is common. Myositis is an extremely rare occurrence and this is the only documented case where the initial presentation of melioidosis has been myositis and later complicated to myonecrosis.

Case presentation

A 45-year-old gentleman with pre-existing diabetes presented with a tender, right thigh lump for 1 week duration without any history of trauma or infection. Investigations revealed neutrophil leukocytosis, high erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels whilst ultrasonography showed focal myositis of right quadriceps. The patient went into sepsis amidst antibacterial treatment which warranted urgent surgery. At surgery, a large intramuscular abscess with myonecrosis was observed within vastus medialis which was completely drained and pus was taken for culture which eventually isolated Burkholderia pseudomallei. Melioidosis was diagnosed and intravenous meropenem was prescribed for 3 weeks. Following complete recovery, the patient was discharged on doxycycline and trimethoprim sulfamethoxazole for 3 months.

Conclusions

Melioidosis, an endemic disease in south east Asia and northern Australia, is an emerging infection in Sri Lanka. Myositis is a rare presentation of the disease that can lead to myonecrosis and abscess formation which can cause rapid disease escalation and sepsis. Early surgical intervention may be life-saving in such cases where antibiotic therapy alone may not suffice.

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Abstract

Background

Human immunodeficiency virus (HIV) contributes significantly to morbidity and mortality in South Africa. Pneumonia and opportunistic infections remain a major cause for hospital admission among those living with HIV, even in the era of the widespread availability of antiretroviral therapy.

Methods

In this retrospective cohort study, the records of patients admitted with HIV and severe pneumonia, requiring high care/intensive care admission, during a period of 12 months (February 2018 to January 2019) were reviewed. Demographic details, antiretroviral use, HIV viral load, CD4 count, sputum culture results and radiological imaging of patients were recorded. Data was analysed to determine variables associated with mortality.

Results

One hundred and seventeen patient records were reviewed for this study. The patients were young (mean age 38.3 years), had advanced disease with low CD4 counts (mean 120.2 cells/mm3) and high HIV viral loads (mean 594,973.7 copies/mL). Only 36.9% (42/117) were on highly active antiretroviral therapy (HAART) on presentation to the hospital. Mycobacterium tuberculosis (M. tuberculosis) was found to be the cause for pneumonia in 35% (41/117), whilst Pneumocystis jirovecii (P. jirovecii) was found in 21.4% (25/117). Bacterial pneumonia was the cause in 17.1% (20/117) of patients while no specific aetiology was found in 26.6% (31/117) of patients in the cohort. Mortality among the cohort studied was high (40.1%) and the average length of stay in hospital in excess of two weeks. The need for ICU admission, ventilation and CMV viremia was associated with increased mortality. Chest X-ray findings did not correlate with the aetiology of pneumonia, but multiple B-lines on lung ultrasound correlated with P. jirovecii as an aetiology and there was a signal that pleural effusion with fibrin stranding predicts tuberculosis.

Conclusions

Patients studied presented with advanced HIV and were often naïve to antiretroviral therapy. Mortality in this cohort of young patients was high, which emphasis the need for earlier diagnosis and treatment of HIV at a primary care level. Lung ultrasound may have clinical utility in the management of patients with HIV and pneumonia, particularly to diagnose P. jirovecii as an aetiology.

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Objective

To describe the epidemiology and risk factors for hospitalisation and death in Mexican children under 18 years of age with COVID-19.

Design

Retrospective, cross-sectional and analytical study.

Setting

Mexican Ministry of Health open databases with COVID-19 cases occurred from 7 March 2020 to 30 September 2021.

Participants

Mexican children under 18 years of age with COVID-19.

Main outcome measures

COVID-19 hospitalisations and deaths were characterised by age group, sex, presence of pneumonia and comorbidities, intubation and intensive care unit admission, and institution that provided medical care. Cumulative incidence, mortality, case fatality rates and ORs for hospitalisation and death were estimated by age group.

Results

5.5% (204 641) of national COVID-19 cases were children under 18 years of age: 2.9% under 1 year, 12.5% from 1 to 5 years, 15% from 6 to 9 years and 69.4% from 10 to 17 years. 4.6% of all cases were hospitalised, from which 54.6% were male, 35.3% were children under 1 year old, 39.6% were adolescents and 34% had pneumonia. Pneumonia developed in 2.3% of cases, from which 50% were adolescents. Case fatality rate was higher in children less than 1 year old (4.2%). Risk analyses showed that male sex (OR 1.16–1.28), history of pneumonia (OR 29.7–65.4), immunosuppression (OR 5.3–42.9), cardiovascular disease (OR 4.4–14.6) and other comorbidities (OR 5.4–19.1), as well as age less than 1 year (OR 20.1, 95% CI 18.8 to 21.4), confer a greater risk of hospitalisation; in addition to comorbidities, age less than 1 year (OR 16.6, 95% CI 14.1 to 19.6), history of pneumonia (OR 14.1–135.1) and being an adolescent from an indigenous community (OR 2.6, 95% CI 1.23 to 5.54, p=0.012) increase the risk of death.

Conclusions

In Mexico, children less than 1 year old with COVID-19 have higher risk of hospitalisation and death than older children. Adolescents with COVID-19 in association with comorbidities develop adverse outcomes more frequently.

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Abstract

Background

Melioidosis caused by Burkholderia pseudomallei is an emerging infection in Sri Lanka with a high case fatality rate. The disease usually manifests as pneumonia, however multisystem involvement is common. Myositis is an extremely rare occurrence and this is the only documented case where the initial presentation of melioidosis has been myositis and later complicated to myonecrosis.

Case presentation

A 45-year-old gentleman with pre-existing diabetes presented with a tender, right thigh lump for 1 week duration without any history of trauma or infection. Investigations revealed neutrophil leukocytosis, high erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels whilst ultrasonography showed focal myositis of right quadriceps. The patient went into sepsis amidst antibacterial treatment which warranted urgent surgery. At surgery, a large intramuscular abscess with myonecrosis was observed within vastus medialis which was completely drained and pus was taken for culture which eventually isolated Burkholderia pseudomallei. Melioidosis was diagnosed and intravenous meropenem was prescribed for 3 weeks. Following complete recovery, the patient was discharged on doxycycline and trimethoprim sulfamethoxazole for 3 months.

Conclusions

Melioidosis, an endemic disease in south east Asia and northern Australia, is an emerging infection in Sri Lanka. Myositis is a rare presentation of the disease that can lead to myonecrosis and abscess formation which can cause rapid disease escalation and sepsis. Early surgical intervention may be life-saving in such cases where antibiotic therapy alone may not suffice.

…

Abstract

Background

Human immunodeficiency virus (HIV) contributes significantly to morbidity and mortality in South Africa. Pneumonia and opportunistic infections remain a major cause for hospital admission among those living with HIV, even in the era of the widespread availability of antiretroviral therapy.

Methods

In this retrospective cohort study, the records of patients admitted with HIV and severe pneumonia, requiring high care/intensive care admission, during a period of 12 months (February 2018 to January 2019) were reviewed. Demographic details, antiretroviral use, HIV viral load, CD4 count, sputum culture results and radiological imaging of patients were recorded. Data was analysed to determine variables associated with mortality.

Results

One hundred and seventeen patient records were reviewed for this study. The patients were young (mean age 38.3 years), had advanced disease with low CD4 counts (mean 120.2 cells/mm3) and high HIV viral loads (mean 594,973.7 copies/mL). Only 36.9% (42/117) were on highly active antiretroviral therapy (HAART) on presentation to the hospital. Mycobacterium tuberculosis (M. tuberculosis) was found to be the cause for pneumonia in 35% (41/117), whilst Pneumocystis jirovecii (P. jirovecii) was found in 21.4% (25/117). Bacterial pneumonia was the cause in 17.1% (20/117) of patients while no specific aetiology was found in 26.6% (31/117) of patients in the cohort. Mortality among the cohort studied was high (40.1%) and the average length of stay in hospital in excess of two weeks. The need for ICU admission, ventilation and CMV viremia was associated with increased mortality. Chest X-ray findings did not correlate with the aetiology of pneumonia, but multiple B-lines on lung ultrasound correlated with P. jirovecii as an aetiology and there was a signal that pleural effusion with fibrin stranding predicts tuberculosis.

Conclusions

Patients studied presented with advanced HIV and were often naïve to antiretroviral therapy. Mortality in this cohort of young patients was high, which emphasis the need for earlier diagnosis and treatment of HIV at a primary care level. Lung ultrasound may have clinical utility in the management of patients with HIV and pneumonia, particularly to diagnose P. jirovecii as an aetiology.

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American Journal of Respiratory and Critical Care Medicine, Volume 205, Issue 12, Page 1429-1439, June 15, 2022. …

Objectives

To determine the disease burden of acute lower respiratory tract disease (aLRTD) and its subsets (pneumonia, lower respiratory tract infection (LRTI) and heart failure) in hospitalised adults in Bristol, UK.

Setting

Single-centre, secondary care hospital, Bristol, UK.

Design

We estimated aLRTD hospitalisations incidence in adults (≥18 years) in Bristol, UK, using two approaches. First, retrospective International Classification of Diseases 10th revision (ICD-10) code analysis (first five positions/hospitalisation) identified aLRTD events over a 12-month period (March 2018 to February 2019). Second, during a 21-day prospective review (19 August 2019 to 9 September 2019), aLRTD admissions were identified, categorised by diagnosis and subsequently annualised. Hospital catchment denominators were calculated using linked general practice and hospitalisation data, with each practice’s denominator contribution calculated based on practice population and per cent of the practices’ hospitalisations admitted to the study hospital.

Participants

Prospective review: 1322 adults screened; 410 identified with aLRTD. Retrospective review: 7727 adult admissions.

Primary and secondary outcome measures

The incidence of aLRTD and its subsets in the adult population of Southmead Hospital, Bristol UK.

Results

Based on ICD-10 code analysis, annual incidences per 100 000 population were: aLRTD, 1901; pneumonia, 591; LRTI, 739; heart failure, 402. aLRTD incidence was highest among those ≥65 years: 65–74 (3684 per 100 000 adults), 75–84 (6962 per 100 000 adults) and ≥85 (11 430 per 100 000 adults). During the prospective review, 410/1322 (31%) hospitalised adults had aLRTD signs/symptoms and annualised incidences closely replicated retrospective analysis results.

Conclusions

The aLRTD disease burden was high, increasing sharply with age. The aLRTD incidence is probably higher than estimated previously due to criteria specifying respiratory-specific symptoms or radiological change, usage of only the first diagnosis code and mismatch between case count sources and population denominators. This may have significant consequences for healthcare planning, including usage of current and future vaccinations against respiratory infection.

…

Introduction

Dysphagia is a common functional disorder after stroke. Most patients post-stroke are incapable of oral feeding, which often leads to complications such as malnutrition, aspiration pneumonia and dehydration that seriously affect the quality of life of patients. Oropharyngeal muscle strength training is a major method of swallowing training, and recent studies have focused on healthy adults, elderly persons, and patients with head and neck cancer or neurodegenerative diseases; but there have been few studies on such training in patients with post-stroke dysphagia. Our study aims to systematically review the safety and performance of oropharyngeal muscle strength training in the treatment of post-stroke dysphagia during oral feeding.

Methods and analysis

The Cochrane Library, Web of Science, PubMed, Embase and ClinicalTrials.gov databases will be systematically searched, and all relevant articles in English from the establishment of the databases to January 2022 will be reviewed. The study will be conducted in accordance with the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and will be reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The primary outcome measures include the Penetration–Aspiration Scale and the Functional Oral Intake Scale. Two authors will independently screen the articles, extract the data and assess the study quality. Any disagreements during this process will be resolved by discussion or by consultation with a third author. Next, quantitative or qualitative, subgroup and sensitivity analyses of the included literature data will be performed as appropriate.

Ethics and dissemination

Ethical approval is not required for this systematic review as no primary data collection will be required. The results of the present study will be published in a peer-reviewed journal in the field of deglutition disorders.

PROSPERO registration number

CRD42022302471.

…

Abstract

Background

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection. In non-HIV immunocompromised patients with PCP, a standard second-line treatment has not been established up to now.

Methods

Non-HIV immunocompromised patients with confirmed PCP between April 2013 and December 2020 were included. Their PCP treatment history was tracked. Factors related to first-line trimethoprim/sulfamethoxazole (TMP/SMX) and second-line treatment failure were identified. Different second-line treatment strategies were compared.

Results

Among the 220 patients, 127 (57.73%) did not respond to first-line TMP/SMX treatment. Risk factors related to treatment failure included symptom triad with breathlessness at rest, persistent fever and cough (85% in the treatment failure group versus 74% in the treatment success group, P = 0.034), treatment with invasive mechanical ventilation (67 vs. 19%, P < 0.001), coinfection with CMV (69 vs. 47%, P = 0.035), and bacteremia (59 vs. 10%, P < 0.001). A total of 49 patients received second-line treatment on the basis of TMP/SMX, and 28 (57.1%) of them responded to the treatment. No clinical parameter, including selection of different therapies, was found to be significantly associated with second-line treatment failure. Further, the prognosis of different second-line therapies showed no drug or drug combination strategy superior to others. The primaquine group had lower 90-day mortality rate (45.9%) but showed no statistically significant difference compared with the non-primaquine group (64.6%). The patients in the clindamycin plus primaquine group had the lowest in-hospital mortality rate (22.2%, P = 0.042) among different second-line therapies, although the in-hospital mortality of the primaquine group was not significantly different from that of the non-primaquine group. The differences in 28 day mortality and overall mortality rates were not statistically significant, too.

Conclusion

CMV infection and bacteremia were risk factors significantly associated with treatment failure of TMP/SMX. The response and survival rates of second-line treatment, including clindamycin, primaquine, and caspofungin, were poor, maybe clindamycin plus primaquine as second line treatment was better than other treatment strategies. These results suggest that clinicians should carefully evaluate whether the treatment of TMP/SMX has failed due to a coinfection rather than hastily changing to a second-line drug when the patient worsens.

…

by Mariana Brena Souza, Maria Cecília Cergole-Novella, Delma Aparecida Molinari, Daniela Rodrigues Colpas, Andréia Moreira dos Santos Carmo, Vilma dos Santos Menezes Gaiotto Daros, Ivana Barros de Campos

Meningitis caused by Streptococcus pneumoniae is still a disease of great impact on Public health, which requires immediate diagnosis and treatment. However, the culture of clinical specimens is often negative and antibiotic susceptibility testing (AST) must be performed with isolated strains. Multiplex real-time polymerase chain reaction (qPCR) has high sensitivity and specificity, produces faster results to identify the pathogen, and it can also be an important tool to identify resistance antibiotic genes earlier than AST, especially in the absence of an isolated strain. This study developed a multiplex qPCR assay, using SYBR Green as a nonspecific dye, to detect antibiotic resistance genes to predict pneumococcal susceptibility/resistance in cerebrospinal fluid (CSF) samples from meningitis patients. From 2017 to 2020, CSF samples were cultured and analyzed by qPCR to detect the main three bacteria causing meningitis. Isolated and reference strains were applied in SYBR Green qPCR multiplex to detect pbp2b, ermB, and mef genes, and the results were compared with the AST. Pneumococcal-positive CSF samples (lytA-positive gene) without isolated strains were also tested to evaluate the antimicrobial susceptibility profile in the region from 2014 to 2020. From the received 873 CSF samples; 263 were cultivated, 149 were lytA-positive in the qPCR, and 25 produced viable isolated pneumococci strains, which were evaluated by AST. Melting temperature for each gene and the acceptance criteria were determined (pbp2b: 78.24–79.86; ermB: 80.88–82.56; mef: 74.85–76.34 ºC). A total of 48/51 strains presented a genetic profile in agreement with the AST results. Resistant strains to erythromycin and clindamycin were ermB-positive, and two were also mef-positive, indicating both resistance mechanisms were present. In the retrospective study of the genetic profile of resistance, 82 lytA-positive CSF samples plus 4 strains were applied in the SYBR Green qPCR multiplex: 51% of samples presented the wild genotype (pbp2b positive and ermB/mef negative); 15% were negative for all the three evaluated, indicating pneumococci resistant to penicillin; and 17% represented the multidrug-resistant pneumococci (pbp2b negative and ermB positive or pbp2b negative and ermB and mef positive). Therefore, SYBR Green qPCR multiplex proved to be a reliable tool to identify resistance genes in S. pneumoniae and would be less expensive than multiplex qPCR using specific probes. This could be easily introduced into the routine of diagnostic laboratories and provide a strong presumption of pneumococcal resistance, especially in the absence of isolated strains.

Abstract

Background

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection. In non-HIV immunocompromised patients with PCP, a standard second-line treatment has not been established up to now.

Methods

Non-HIV immunocompromised patients with confirmed PCP between April 2013 and December 2020 were included. Their PCP treatment history was tracked. Factors related to first-line trimethoprim/sulfamethoxazole (TMP/SMX) and second-line treatment failure were identified. Different second-line treatment strategies were compared.

Results

Among the 220 patients, 127 (57.73%) did not respond to first-line TMP/SMX treatment. Risk factors related to treatment failure included symptom triad with breathlessness at rest, persistent fever and cough (85% in the treatment failure group versus 74% in the treatment success group, P = 0.034), treatment with invasive mechanical ventilation (67 vs. 19%, P < 0.001), coinfection with CMV (69 vs. 47%, P = 0.035), and bacteremia (59 vs. 10%, P < 0.001). A total of 49 patients received second-line treatment on the basis of TMP/SMX, and 28 (57.1%) of them responded to the treatment. No clinical parameter, including selection of different therapies, was found to be significantly associated with second-line treatment failure. Further, the prognosis of different second-line therapies showed no drug or drug combination strategy superior to others. The primaquine group had lower 90-day mortality rate (45.9%) but showed no statistically significant difference compared with the non-primaquine group (64.6%). The patients in the clindamycin plus primaquine group had the lowest in-hospital mortality rate (22.2%, P = 0.042) among different second-line therapies, although the in-hospital mortality of the primaquine group was not significantly different from that of the non-primaquine group. The differences in 28 day mortality and overall mortality rates were not statistically significant, too.

Conclusion

CMV infection and bacteremia were risk factors significantly associated with treatment failure of TMP/SMX. The response and survival rates of second-line treatment, including clindamycin, primaquine, and caspofungin, were poor, maybe clindamycin plus primaquine as second line treatment was better than other treatment strategies. These results suggest that clinicians should carefully evaluate whether the treatment of TMP/SMX has failed due to a coinfection rather than hastily changing to a second-line drug when the patient worsens.

…

Abstract

Background

The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers.

Methods

This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables.

Results

A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26–6.24), p = 0.01].

Conclusions

These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.

…

Antimicrobial Agents and Chemotherapy, Ahead of Print. …

Abstract

Background

The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers.

Methods

This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables.

Results

A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26–6.24), p = 0.01].

Conclusions

These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.

…

Abstract

Background

The empirical prescription of antibiotics to inpatients with Coronavirus Disease 2019 (COVID-19) is frequent despite uncommon bacterial coinfections. Current knowledge of the effect of antibiotics on the survival of hospitalized children with COVID-19 is limited.

Objective

To characterize the survival experience of children with laboratory-positive COVID-19 in whom antibiotics were prescribed at hospital admission.

Methods

A retrospective cohort study was conducted in Mexico, with children hospitalized due to COVID-19 from March 2020 to December 2021. Data from 1601 patients were analyzed using the Kaplan–Meier method and the log-rank test. We computed hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the effect of the analyzed exposures on disease outcomes.

Results

Antibiotics were prescribed to 13.2% (

(n)

= 211) of enrolled children and a higher mortality rate [14.9 (95% CI 10.1–19.8) vs. 8.3 (95% CI 6.8–9.8)] per 1000 person-days,

(p)

< 0.001) was found among them. At any given cut-off, survival functions were lower in antibiotic-positive inpatients (

(p)

< 0.001). In the multiple model, antibiotic prescription was associated with a 50% increase in the risk of fatal outcome (HR = 1.50, 95% CI 1.01–2.22). A longer interval between illness onset and healthcare-seeking and pneumonia at hospital admission was associated with a poorer prognosis.

Conclusions

Our results suggest that antibiotic prescription in children hospitalized due to COVID-19 is associated with decreased survival. If later replicated, these findings highlight the need for rational antibiotics in these patients.

…

Abstract

Background

The empirical prescription of antibiotics to inpatients with Coronavirus Disease 2019 (COVID-19) is frequent despite uncommon bacterial coinfections. Current knowledge of the effect of antibiotics on the survival of hospitalized children with COVID-19 is limited.

Objective

To characterize the survival experience of children with laboratory-positive COVID-19 in whom antibiotics were prescribed at hospital admission.

Methods

A retrospective cohort study was conducted in Mexico, with children hospitalized due to COVID-19 from March 2020 to December 2021. Data from 1601 patients were analyzed using the Kaplan–Meier method and the log-rank test. We computed hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the effect of the analyzed exposures on disease outcomes.

Results

Antibiotics were prescribed to 13.2% (

(n)

= 211) of enrolled children and a higher mortality rate [14.9 (95% CI 10.1–19.8) vs. 8.3 (95% CI 6.8–9.8)] per 1000 person-days,

(p)

< 0.001) was found among them. At any given cut-off, survival functions were lower in antibiotic-positive inpatients (

(p)

< 0.001). In the multiple model, antibiotic prescription was associated with a 50% increase in the risk of fatal outcome (HR = 1.50, 95% CI 1.01–2.22). A longer interval between illness onset and healthcare-seeking and pneumonia at hospital admission was associated with a poorer prognosis.

Conclusions

Our results suggest that antibiotic prescription in children hospitalized due to COVID-19 is associated with decreased survival. If later replicated, these findings highlight the need for rational antibiotics in these patients.

…

by Luke Bracegirdle, Alexander Jackson, Ryan Beecham, Maria Burova, Elsie Hunter, Laura G. Hamilton, Darshni Pandya, Clare Morden, Michael P. W. Grocott, Andrew Cumpstey, Ahilanandan Dushianthan, the REACT COVID-19 Investigators

Background Acute hypoxic respiratory failure (AHRF) is a hallmark of severe COVID-19 pneumonia and often requires supplementary oxygen therapy. Critically ill COVID-19 patients may require invasive mechanical ventilation, which carries significant morbidity and mortality. Understanding of the relationship between dynamic changes in blood oxygen indices and clinical variables is lacking. We evaluated the changes in blood oxygen indices–PaO2, PaO2/FiO2 ratio, oxygen content (CaO2) and oxygen extraction ratio (O2ER) in COVID-19 patients through the first 30-days of intensive care unit admission and explored relationships with clinical outcomes. Methods and findings We performed a retrospective observational cohort study of all adult COVID-19 patients in a single institution requiring invasive mechanical ventilation between March 2020 and March 2021. We collected baseline characteristics, clinical outcomes and blood oxygen indices. 36,383 blood gas data points were analysed from 184 patients over 30-days. Median participant age was 59.5 (IQR 51.0, 67.0), BMI 30.0 (IQR 25.2, 35.5) and the majority were men (62.5%) of white ethnicity (70.1%). Median duration of mechanical ventilation was 15-days (IQR 8, 25). Hospital survival at 30-days was 72.3%. Non-survivors exhibited significantly lower PaO2 throughout intensive care unit admission: day one to day 30 averaged mean difference -0.52 kPa (95% CI: -0.59 to -0.46, p<0.01). Non-survivors exhibited a significantly lower PaO2/FiO2 ratio with an increased separation over time: day one to day 30 averaged mean difference -5.64 (95% CI: -5.85 to -5.43, p<0.01). While all patients had sub-physiological CaO2, non-survivors exhibited significantly higher values. Non-survivors also exhibited significantly lower oxygen extraction ratio with an averaged mean difference of -0.08 (95% CI: -0.09 to -0.07, p<0.01) across day one to day 30. Conclusions As a novel cause of acute hypoxic respiratory failure, COVID-19 offers a unique opportunity to study a homogenous cohort of patients with hypoxaemia. In mechanically ventilated adult COVID-19 patients, blood oxygen indices are abnormal with substantial divergence in PaO2/FiO2 ratio and oxygen extraction ratio between survivors and non-survivors. Despite having higher CaO2 values, non-survivors appear to extract less oxygen implying impaired oxygen utilisation. Further exploratory studies are warranted to evaluate and improve oxygen extraction which may help to improve outcomes in severe hypoxaemic mechanically ventilated COVID-19 patients.…

A 52-year-old woman with a 10-day history of a fever and who had, for the past 4 days, an impaired level of consciousness attended our hospital.

Streptococcus pneumoniae can cause Invasive pneumococcal disease (IPD) at a patient's sterile site, including the cerebrospinal fluid and blood, and commonly presents with septicemia, meningitis, and pneumonia (Dowell et al., 2003). In Japan, both children and the elderly receive public support for pneumococcal vaccination. Pneumococcal vaccine coverage has been increased since the launch of the vaccine program (Naito et al., 2020).

Abstract

Background

Bacterial opportunistic infections are common in people living with HIV/AIDS (PLHA). Besides HIV-TB co-infection, lower respiratory tract infections (LRTIs) due to multidrug-resistant (MDR) bacteria cause significant morbidity and mortality among PLHA. This study identified bacterial co-infection of the lower respiratory tract and detected plasmid-mediated blaTEM and blaCTX-M genes among Extended-Spectrum β-Lactamase (ESBL) producing isolates from sputum samples in PLHA.

Methods

A total of 263 PLHA with LRTIs were enrolled in this study, out of which, 50 were smokers, 70 had previous pulmonary tuberculosis, and 21 had CD4 count < 200 cells/µl. Sputum samples collected from PLHA were processed with standard microbiological methods to identify the possible bacterial pathogens. The identified bacterial isolates were assessed for antibiotic susceptibility pattern using modified Kirby Bauer disk diffusion method following Clinical Laboratory Standard Institute (CLSI) guidelines. In addition, plasmid DNA was extracted from MDR and ESBL producers for screening of ESBL genes; blaCTX-M and blaTEM by conventional PCR method using specific primers.

Results

Of 263 sputum samples, 67 (25.48%) showed bacterial growth. Among different bacterial pathogens, Klebsiella pneumoniae, (17; 25.37%) was the most predominant, followed by Haemophillus influenzae, (14; 20.90%) and Escherichia coli, (12; 17.91%). A higher infection rate (4/8; 50%) was observed among people aged 61–70 years, whereas no infection was observed below 20 years. About 30.0% (15/50) of smokers, 32.86% (23/70) cases with previous pulmonary tuberculosis, and 52.38% (11/21) with CD4 count < 200 cells/µl had bacterial LRTIs. Among 53 bacterial isolates excluding H. influenzae, 28 isolates were MDR and 23 were ESBL producers. All ESBL producers were sensitive to colistin and polymyxin B. Among ESBL producers, 47.83% (11/23) possessed blaCTX-M, 8.6% (2/23) were positive for blaTEM gene, and 43.48% (10/23) possessed both ESBL genes.

Conclusion

The increasing rate of MDR bacterial infections, mainly ESBL producers of LRTIs causes difficulty in disease management, leading to high morbidity and mortality of PLHA. Hence, it is crucial to know the antibiogram pattern of the isolates to recommend effective antimicrobial therapy to treat LRTIs in PLHA.

…

Abstract

Background

Bacterial opportunistic infections are common in people living with HIV/AIDS (PLHA). Besides HIV-TB co-infection, lower respiratory tract infections (LRTIs) due to multidrug-resistant (MDR) bacteria cause significant morbidity and mortality among PLHA. This study identified bacterial co-infection of the lower respiratory tract and detected plasmid-mediated blaTEM and blaCTX-M genes among Extended-Spectrum β-Lactamase (ESBL) producing isolates from sputum samples in PLHA.

Methods

A total of 263 PLHA with LRTIs were enrolled in this study, out of which, 50 were smokers, 70 had previous pulmonary tuberculosis, and 21 had CD4 count < 200 cells/µl. Sputum samples collected from PLHA were processed with standard microbiological methods to identify the possible bacterial pathogens. The identified bacterial isolates were assessed for antibiotic susceptibility pattern using modified Kirby Bauer disk diffusion method following Clinical Laboratory Standard Institute (CLSI) guidelines. In addition, plasmid DNA was extracted from MDR and ESBL producers for screening of ESBL genes; blaCTX-M and blaTEM by conventional PCR method using specific primers.

Results

Of 263 sputum samples, 67 (25.48%) showed bacterial growth. Among different bacterial pathogens, Klebsiella pneumoniae, (17; 25.37%) was the most predominant, followed by Haemophillus influenzae, (14; 20.90%) and Escherichia coli, (12; 17.91%). A higher infection rate (4/8; 50%) was observed among people aged 61–70 years, whereas no infection was observed below 20 years. About 30.0% (15/50) of smokers, 32.86% (23/70) cases with previous pulmonary tuberculosis, and 52.38% (11/21) with CD4 count < 200 cells/µl had bacterial LRTIs. Among 53 bacterial isolates excluding H. influenzae, 28 isolates were MDR and 23 were ESBL producers. All ESBL producers were sensitive to colistin and polymyxin B. Among ESBL producers, 47.83% (11/23) possessed blaCTX-M, 8.6% (2/23) were positive for blaTEM gene, and 43.48% (10/23) possessed both ESBL genes.

Conclusion

The increasing rate of MDR bacterial infections, mainly ESBL producers of LRTIs causes difficulty in disease management, leading to high morbidity and mortality of PLHA. Hence, it is crucial to know the antibiogram pattern of the isolates to recommend effective antimicrobial therapy to treat LRTIs in PLHA.

…

Objectives

Despite progress made to expand access to health service in Ghana, inequities still exist. Social innovations have been developed as community-engaged solutions to decrease inequities.

Methods

In partnership with a multistakeholder group, our social innovation team organised a crowdsourcing contest to identify health innovations in Ghana. Informed by a WHO-Special Programme for Research and Training in Tropical Diseases framework, we organised a six-stage crowdsourcing challenge.

Results

In all, 13 innovations were received in the contest, while 2 innovations were rejected after initial screening. The 11 innovations were reviewed by a panel of four independent expert judges. Inter-rated reliability index (kappa) was 0.86. Following the review of the average score, five top innovations were recognised. These submissions can be put into three main themes: technology and strengthening (eg, mHealth for cervical cancer screening, video directly observed therapy), inclusiveness and reaching the marginalised (people with disability and infertility) and data utilisation for project improvement (seasonal calendar to reduce morbidity and mortality of children under 5 for malaria, diarrhoea and pneumonia).

Conclusion

In conclusion, this study shows that solutions to local problems exist. Therefore, policymakers, the government and development partners should support the scale-up of such innovations.

…

Abstract

Background

Blood cultures remain the gold standard investigation for the diagnosis of bloodstream infections. In many locations, quality-assured processing of positive blood cultures is not possible. One solution is to incubate blood cultures locally, and then transport bottles that flag positive to a central reference laboratory for organism identification and antimicrobial susceptibility testing. However, the impact of delay between the bottle flagging positive and subsequent sub-culture on the viability of the isolate has received little attention.

Methods

This study evaluated the impact of delays to sub-culture (22 h to seven days) in three different temperature conditions (2–8 °C, 22–27 °C and 35 ± 2 °C) for bottles that had flagged positive in automated detection systems using a mixture of spiked and routine clinical specimens. Ninety spiked samples for five common bacterial causes of sepsis (Escherichia coli, Haemophilus influenzae, Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae) and 125 consecutive positive clinical blood cultures were evaluated at four laboratories located in Cambodia, Lao PDR and Thailand. In addition, the utility of transport swabs for preserving organism viability was investigated.

Results

All organisms were recoverable from all sub-cultures in all temperature conditions with the exception of S. pneumoniae, which was less likely to be recoverable after longer delays (> 46–50 h), when stored in hotter temperatures (35 °C), and from BacT/ALERT when compared with BACTEC blood culture bottles. Storage of positive blood culture bottles in cooler temperatures (22–27 °C or below) and the use of Amies bacterial transport swabs helped preserve viability of S. pneumoniae.

Conclusions

These results have practical implications for the optimal workflow for blood culture bottles that have flagged positive in automated detection systems located remotely from a central processing laboratory, particularly in tropical resource-constrained contexts.

…

Abstract

Purpose

To investigate the prevalence of neuro-functional disability and its determinants 12 months after community-acquired bacterial meningitis (CABM) in adult patients.

Methods

In a prospective multicenter cohort study (COMBAT), all consecutive cases of CABM were enrolled and followed up for 12 months. Neuro-functional disability at 12 months was evaluated using a combination of the Glasgow Outcome Scale (functional disability), and the modified Rankin Disability Scale (physical disability). Factors associated with neuro-functional disability were identified by multivariate logistic regression.

Results

Among 281 patients, 84 (29.9%) patients exhibited neuro-functional disability at 12 months: 79 (28.1%) with functional disability and 51 (18.1%) with physical disability. Overall, 6 patients (2.1%) died during the follow-up. The most common pathogen identified was Streptococcus pneumoniae (131/272, 48.2%); 77/268 patients (28.7%) had a physical disability at hospital discharge. Factors independently associated with 12-month neuro-functional disability were a pneumococcal meningitis (adjusted OR = 2.8; 95% confidence interval (CI) = [1.3; 6.7]), the presence of a physical disability at hospital discharge (aOR = 2.3; 95%CI = [1.2; 4.4]) and the presence of behavioral disorders at hospital-discharge (aOR = 5.9; 95%CI = [1.6; 28.4]). Dexamethasone use was not significantly associated with neuro-functional disability (OR = 0.2; 95%CI = [< 0.1;1.3]).

Conclusion

Neuro-functional disability is frequently reported 12 months after CABM. Detailed neurological examination at discharge is needed to improve the follow-up.

Trial registration

NCT01730690.

…

Abstract

Background

Blood cultures remain the gold standard investigation for the diagnosis of bloodstream infections. In many locations, quality-assured processing of positive blood cultures is not possible. One solution is to incubate blood cultures locally, and then transport bottles that flag positive to a central reference laboratory for organism identification and antimicrobial susceptibility testing. However, the impact of delay between the bottle flagging positive and subsequent sub-culture on the viability of the isolate has received little attention.

Methods

This study evaluated the impact of delays to sub-culture (22 h to seven days) in three different temperature conditions (2–8 °C, 22–27 °C and 35 ± 2 °C) for bottles that had flagged positive in automated detection systems using a mixture of spiked and routine clinical specimens. Ninety spiked samples for five common bacterial causes of sepsis (Escherichia coli, Haemophilus influenzae, Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae) and 125 consecutive positive clinical blood cultures were evaluated at four laboratories located in Cambodia, Lao PDR and Thailand. In addition, the utility of transport swabs for preserving organism viability was investigated.

Results

All organisms were recoverable from all sub-cultures in all temperature conditions with the exception of S. pneumoniae, which was less likely to be recoverable after longer delays (> 46–50 h), when stored in hotter temperatures (35 °C), and from BacT/ALERT when compared with BACTEC blood culture bottles. Storage of positive blood culture bottles in cooler temperatures (22–27 °C or below) and the use of Amies bacterial transport swabs helped preserve viability of S. pneumoniae.

Conclusions

These results have practical implications for the optimal workflow for blood culture bottles that have flagged positive in automated detection systems located remotely from a central processing laboratory, particularly in tropical resource-constrained contexts.

…

Objectives

The objective of this study was to model the clinical and economic impact of adapting current clinical practice in the management of patients with chronic obstructive pulmonary disease (COPD) to treatment according to national and international guideline recommendations.

Design

Treatment mapping was undertaken to hypothetically redistribute patients from current clinical practice, representing actual prescribing patterns in the UK, to an alternative recommendation-based treatment scenario, representing prescribing in accordance with either National Institute for Health and Care Excellence (NICE) guidance [NG115] or Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 strategy.

Setting

Primary care practices in the UK (1-year time horizon).

Participants

Adults with COPD undergoing long-acting inhaler maintenance therapy in the UK (N=1 067,531).

Interventions

Inhaler maintenance therapy.

Outcome measures

Costs and clinical outcomes (type of treatment, rates of moderate and/or severe exacerbations, and mild-to-moderate and/or severe pneumonia events) were modelled for the two alternative pathways.

Results

Compared with current clinical practice, treating patients according to NICE guidance resulted in an estimated annual reduction in expenditure of £46.9 million, and an estimated annual reduction in expenditure of over £43.7 million when patients were treated according to GOLD 2020 strategy. Total cost savings of up to 8% annually could be achieved by treatment of patients according to either of these recommendations. Cost savings arose from a reduction in the rates of pneumonia, with an associated decrease in costs associated with antibiotic use and hospitalisation. Savings were achieved overall despite a small increase in the rate of exacerbations due to the redistribution of certain patients currently undergoing triple inhaled therapy to therapies not containing inhaled corticosteroids.

Conclusion

Redistribution of patients with COPD from current clinical practice to treatment according to published recommendations would provide substantial cost savings over the first year.

…

Abstract

Purpose

To investigate the prevalence of neuro-functional disability and its determinants 12 months after community-acquired bacterial meningitis (CABM) in adult patients.

Methods

In a prospective multicenter cohort study (COMBAT), all consecutive cases of CABM were enrolled and followed up for 12 months. Neuro-functional disability at 12 months was evaluated using a combination of the Glasgow Outcome Scale (functional disability), and the modified Rankin Disability Scale (physical disability). Factors associated with neuro-functional disability were identified by multivariate logistic regression.

Results

Among 281 patients, 84 (29.9%) patients exhibited neuro-functional disability at 12 months: 79 (28.1%) with functional disability and 51 (18.1%) with physical disability. Overall, 6 patients (2.1%) died during the follow-up. The most common pathogen identified was Streptococcus pneumoniae (131/272, 48.2%); 77/268 patients (28.7%) had a physical disability at hospital discharge. Factors independently associated with 12-month neuro-functional disability were a pneumococcal meningitis (adjusted OR = 2.8; 95% confidence interval (CI) = [1.3; 6.7]), the presence of a physical disability at hospital discharge (aOR = 2.3; 95%CI = [1.2; 4.4]) and the presence of behavioral disorders at hospital-discharge (aOR = 5.9; 95%CI = [1.6; 28.4]). Dexamethasone use was not significantly associated with neuro-functional disability (OR = 0.2; 95%CI = [< 0.1;1.3]).

Conclusion

Neuro-functional disability is frequently reported 12 months after CABM. Detailed neurological examination at discharge is needed to improve the follow-up.

Trial registration

NCT01730690.

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Antimicrobial Agents and Chemotherapy, Ahead of Print. …

American Journal of Respiratory and Critical Care Medicine, Volume 205, Issue 11, Page 1267-1268, June 1, 2022. …

American Journal of Respiratory and Critical Care Medicine, Volume 205, Issue 11, Page 1290-1299, June 1, 2022. …

American Journal of Respiratory and Critical Care Medicine, Volume 205, Issue 11, Page 1330-1336, June 1, 2022. …

Pneumonia remains the leading cause of infectious morbidity and mortality in children; however, research remains chronically under-funded and has been excluded from major global financing mechanisms.1 To achieve the Sustainable Development Goals, as set out in the UN 2030 Agenda for Sustainable Development, funding for childhood pneumonia research should be prioritised.

by Maurin Lampart, Núria Zellweger, Stefano Bassetti, Sarah Tschudin-Sutter, Katharina M. Rentsch, Martin Siegemund, Roland Bingisser, Stefan Osswald, Gabriela M. Kuster, Raphael Twerenbold

Background Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing. Objective We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections. Materials and methods Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days. Results Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850–0.948]; AUC for CRP 0.922 [95%CI 0.879–0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694–0.894]; AUC for CRP 0.807 [95%CI 0.721–0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls. Conclusion In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions.…

Abstract

Purpose

Remdesivir is FDA-approved for treatment of patients hospitalized with COVID-19 pneumonia, but not recommended in patients with severe renal failure. This study aims to evaluate the safety of remdesivir in this patient population.

Methods

This was a single-center, retrospective cohort study including patients ≥ 18 years old, admitted between May 1, 2020 and April 30, 2021 who received remdesivir. Patients were divided into two groups: estimated creatinine clearance (eCrCl) < 30 mL/min and eCrCl ≥ 30 ml/min. Primary outcomes were development of acute kidney injury (AKI) after remdesivir initiation and hepatotoxicity (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 5 × upper limit of normal) both at end of treatment (EOT) or 5 days after EOT. Secondary outcomes were length of stay (days) and mortality.

Results

513 patients were assessed with 416 patients included in the study (eCrCl < 30 mL/min, n = 55; eCrCl ≥ 30 mL/min n = 361). Incidence of AKI (eCrCl < 30 mL/min 11% vs eCrCl ≥ 30 mL/min 7%, OR 1.57, 95% CI 0.57, 4.3) and hepatotoxicity (ALT: 2% vs 4%, OR 0.47, 95% CI 0.05, 3.7 and AST: 2% vs 2%, OR 1.26, 95% CI 0.14, 11.04) were similar between the two groups. Length of stay was longer in the eCrCl < 30 mL/min group (mean 18.6 vs 11.9, difference 6.7, 95% CI 3.8, 9.6), and no difference in mortality was observed (21.8% vs 18.8%, OR 1.2, 95% CI 0.6, 2.4).

Conclusion

Remdesivir was not associated with development of AKI or hepatotoxicity in patients with eCrCl < 30 mL/min compared to patients with eCrCl ≥ 30 mL/min, and warrants further investigation.

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