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Objectives:

The use of extracorporeal membrane oxygenation (ECMO) in patients with COVID-19 has been supported by major healthcare organizations, yet the role of specific management strategies during ECMO requires further study. We sought to characterize tracheostomy practices, complications, and outcomes in ECMO-supported patients with acute respiratory failure related to COVID-19.

Design:

Retrospective cohort study.

Setting:

ECMO centers contributing to the Extracorporeal Life Support Organization Registry.

Patients:

Patients 16 years or older receiving venovenous ECMO for respiratory support for: 1) COVID-19 in 2020 and 2021 (through October 2021) and 2) pre-COVID-19 viral pneumonia in 2019.

Interventions:

None.

Measurements and Main Results:

We identified 7,047 patients who received ECMO support for acute respiratory failure related to COVID-19. A total of 32% of patients were recorded as having a tracheostomy procedure during ECMO, and 51% had a tracheostomy at some point during hospitalization. The frequency of tracheostomy was similar in pre-COVID-19 viral pneumonia, but tracheostomies were performed 3 days earlier compared with patients with COVID-19 (median 6.7 d [interquartile range [IQR], 3.0–12.0 d] vs 10.0 d [IQR, 5.0–16.5 d]; p < 0.001). More patients were mobilized with pre-COVID-19 viral pneumonia, but receipt of a tracheostomy during ECMO was associated with increased mobilization in both cohorts. More bleeding complications occurred in patients who received a tracheostomy, with 9% of patients with COVID-19 who received a tracheostomy reported as having surgical site bleeding.

Conclusions:

Tracheostomies are performed in COVID-19 patients receiving ECMO at rates similar to practices in pre-COVID-19 viral pneumonia, although later during the course of ECMO. Receipt of a tracheostomy was associated with increased patient mobilization. Overall mortality was similar between those who did and did not receive a tracheostomy.

Objectives:

We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation.

Design:

Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial.

Setting:

Five U.S. medical centers.

Patients:

Adults inpatients with severe COVID-19 disease and hyperinflammation.

Interventions:

Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo.

Measurements and Main Results:

The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival ,frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR > 1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR > 1] 86.5% and OR = 2.53; p [OR > 1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR] < 1; 99.9%) and ICU admission (OR = 0.26; p [OR < 1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR] < 0.75; p [RR < 1] > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR > 1] 98.1%; OR = 3.36, p [OR > 1] 99.6%; and OR = 3.52, p [OR > 1] 99.8%, respectively).

Conclusions:

Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.

New drugs and methods to efficiently fight carbapenem-resistant Gram-negative pathogens are sorely needed. In this study we characterized the preclinical pharmacokinetics and pharmacodynamics of the clinical-stage drug candidate apramycin in time kill and mouse lung infection models. Based on in vitro and in vivo data, we developed a mathematical model to predict human efficacy.

Surveillance. Detection. Response. The elements of a robust public health system to prevent the next (inevitable) pandemic are well understood. An early warning system for pneumonias of unknown aetiology is of paramount importance. Debates abound about how to deliver these crucial functions. A pandemic treaty. Revisions to the International Health Regulations. The role of WHO. Financing instruments. Workforce. There is little consensus. The sad truth is that political disagreements will tie these questions up in the mucilaginous bureaucracy that is today's global health.

AbstractBackgroundThe optimal treatment duration of community-acquired pneumonia (CAP) in children has been controversial in high-income countries. We conducted a meta-analysis to compare short antibiotic treatment (3–5 days) to longer treatment (7–10 days) among children aged ≥6 months.MethodsOn January 31, 2022, we searched PubMed, Scopus, and Web of Science databases for studies published in English from 2003 to 2022. We included randomized controlled trials focusing on antibiotic treatment duration in children with CAP treated as outpatients. We calculated risk differences (RD) with 95% confidence intervals (CI) and used the fixed effect model (low heterogeneity). Our main outcome was treatment failure, defined as need for re-treatment or hospitalization within 1 month. Our secondary outcome was presence of antibiotic-related harms.Results541 studies were screened and 4 studies with 1541 children were included in the review. Three studies had low risk of bias and one study had some concerns. All 4 studies assessed treatment failures, and the RD was 0.1% (CI -3.0% to 2.0%) with high quality of evidence. Two studies (1194 children) assessed adverse events related to antibiotic treatment, and RD was 0.0% (-5.0% to 5.0%) with moderate quality of evidence. The diagnostic criteria varied between the included studies.ConclusionsA short antibiotic treatment duration of 3–5 days was equally effective and safe compared to the longer (current) recommendation of 7–10 days in children aged over 6 months with CAP. We suggest that short antibiotic courses can be implemented in treatment of pediatric CAP.

Hospital-acquired pneumonia in non-ventilated patients (nvHAP) belongs to the most common healthcare-associated infections. This study aimed to investigate risk factors for nvHAP in patients outside the intensive care unit, focusing on modifiable risk factors.

Abstract

Background

The present study aimed to identify the clinical significance of Mycoplasma pneumoniae (MP)-specific immunoglobulin M (IgM) titer, in addition to a diagnosis of MP infection, in children with MP pneumonia.

Methods

This study was performed in 155 children hospitalized with MP pneumonia. The clinical features and laboratory and radiographic findings on admission in children with positive or negative MP-specific IgM titers were retrospectively reviewed from the electronic medical records.

Results

The mean age of the included children was 6.0 years, and 118 (76.1%) of the children were positive for MP-specific IgM. A longer duration between symptom onset and admission (adjusted odds ratio [aOR] 1.47, 95% confidence interval [CI] 1.24–1.75), longer duration of symptoms during the illness (aOR 1.15, 95% CI 1.02–1.30), and development of extra-pulmonary manifestations (aOR 9.16, 95% CI 1.96–42.81) were significantly associated with a positive MP-specific IgM titer. Serum lactate dehydrogenase levels (aOR 1.00, 95% CI 1.00–1.01) and pneumonic infiltration involving > 50% of the total lung volume on chest radiography (aOR 4.68, 95% CI 1.12–19.55) were associated with positive MP-specific IgM in children with MP pneumonia. A poor response to stepwise treatment for MP pneumonia was more common in children with a positive MP-specific IgM titer than those with a negative MP-specific IgM titer on admission.

Conclusions

A positive MP-specific IgM titer at diagnosis of MP pneumonia may partially suggest an exaggerated immune response with a higher disease burden compared to children with MP pneumonia with a negative MP-specific IgM titer.

…

Abstract

Background

The present study aimed to identify the clinical significance of Mycoplasma pneumoniae (MP)-specific immunoglobulin M (IgM) titer, in addition to a diagnosis of MP infection, in children with MP pneumonia.

Methods

This study was performed in 155 children hospitalized with MP pneumonia. The clinical features and laboratory and radiographic findings on admission in children with positive or negative MP-specific IgM titers were retrospectively reviewed from the electronic medical records.

Results

The mean age of the included children was 6.0 years, and 118 (76.1%) of the children were positive for MP-specific IgM. A longer duration between symptom onset and admission (adjusted odds ratio [aOR] 1.47, 95% confidence interval [CI] 1.24–1.75), longer duration of symptoms during the illness (aOR 1.15, 95% CI 1.02–1.30), and development of extra-pulmonary manifestations (aOR 9.16, 95% CI 1.96–42.81) were significantly associated with a positive MP-specific IgM titer. Serum lactate dehydrogenase levels (aOR 1.00, 95% CI 1.00–1.01) and pneumonic infiltration involving > 50% of the total lung volume on chest radiography (aOR 4.68, 95% CI 1.12–19.55) were associated with positive MP-specific IgM in children with MP pneumonia. A poor response to stepwise treatment for MP pneumonia was more common in children with a positive MP-specific IgM titer than those with a negative MP-specific IgM titer on admission.

Conclusions

A positive MP-specific IgM titer at diagnosis of MP pneumonia may partially suggest an exaggerated immune response with a higher disease burden compared to children with MP pneumonia with a negative MP-specific IgM titer.

…

Abstract

Background

Several cases of coronavirus disease 2019 (COVID-19)-associated leukoencephalopathy have been reported. Although most cases involve hypoxia, the pathophysiological mechanism and neurologic outcomes of COVID-19-associated leukoencephalopathy remain unclear.

Case presentation

We report a case of COVID-19-associated leukoencephalopathy without severe hypoxia in a 65-year-old woman diagnosed with pyelonephritis. After the initiation of intravenous ceftriaxone, her fever resolved, but she developed an altered state of consciousness with abnormal behavior and, subsequently, a relapse fever. She was diagnosed with COVID-19 pneumonia and was intubated. Lung-protective ventilation with deep sedation and neuromuscular blockade were used for treatment. After cessation of sedative administration, her mental status remained at a Glasgow Coma Scale score of 3. COVID-19 was assumed to have caused leukoencephalopathy due to the absence of severe hypoxia or other potential causes. She subsequently showed gradual neurologic improvement. Three months after the COVID-19 diagnosis, she regained alertness, with a Glasgow Coma Scale score of 15.

Conclusion

Clinicians should consider leukoencephalopathy in the differential diagnosis of consciousness disorders in patients with severe COVID-19, even in the absence of severe hypoxia. Gradual neurologic improvement can be expected in such cases.

…

Abstract

Background

Legionella-related community acquired pneumonia (CAP) is a disease with an increasing incidence and a high mortality rate, especially if empirical antibiotic therapy is inadequate. Antibiotic treatment highly relies on clinical symptoms, although proven non-specific, because currently available diagnostic techniques provide insufficient accuracy for detecting Legionella CAP on admission. This study validates a diagnostic scoring system for detection of Legionella-related CAP, based on six items on admission (Legionella prediction score).

Methods

We included patients with Legionella-related CAP admitted to five large Dutch hospitals between 2006 and 2016. Controls were non-Legionella-related CAP patients. The following six conditions were rewarded one point if present: fever > 39.4 °C; dry cough; hyponatremia (sodium) < 133 mmol/L; lactate dehydrogenase (LDH) > 225 mmol/L; C-reactive protein (CRP) > 187 mg/L and platelet count < 171 × 109/L. The accuracy of the prediction score was assessed by calculating the area under the curve (AUC) through logistic regression analysis.

Results

We included 131 cases and 160 controls. A score of 0 occurred in non-Legionella-related CAP patients only, a score of 5 and 6 in Legionella-related CAP patients only. A cut-off ≥ 4 resulted in a sensitivity of 58.8% and a specificity of 93.1%. The AUC was 0.89 (95% CI 0.86–0.93). The strongest predictors were elevated LDH, elevated CRP and hyponatremia.

Conclusions

This multi-centre study validates the Legionella prediction score, an easily applicable diagnostic scoring system, in a large group of patients and finds high diagnostic accuracy. The score shows promise for future prospective validation and could contribute to targeted antibiotic treatment of suspected Legionella CAP.

…

Introduction…

Abstract

Background

Infection with carbapenem-resistant Enterobacterales (CRE) is associated with a high mortality rate in kidney transplant recipients, and colonization with CRE is one of the major risk factors for CRE infection. There is, therefore, a need to improve the capacity to detect colonization with CRE among inpatients.

Methods

In this prospective study, we compared the performance of real-time PCR for carbapenemase directly from rectal swabs with that of conventional CRE surveillance culture in all patients admitted to a kidney transplant ward between February 2019 and March 2020. Surveillance culture and real-time PCR were performed at admission and weekly until hospital discharge. Two perineum-rectal swabs were collected: one for culture and one for PCR.

Results

We collected 905 paired samples for CRE surveillance from 399 patients, of whom 347 (87.0%) were kidney transplant recipients and 52 were waiting list patients. CRE was detected by culture and/or PCR in 75 patients (18.8%). Positivity for CRE was identified by PCR in 62 (15.5%) of the 399 patients and by culture in 55 (13.8%); 20 (5.0%) of the patients tested positive only on PCR, and 13 (3.3%) tested positive only on culture. The most common carbapenemase and species were, respectively, blaKPC (in 85.5%) and Klebsiella pneumoniae (in 80.0%). Infection with CRE occurred in 21.6% of the colonized patients, those cases occurred only among kidney transplant recipients. None of the patients who tested negative on culture developed CRE infection.

Conclusion

In conclusion, the two methods are complementary and could be useful in a scenario of high CRE prevalence.

…

Abstract

Background

Several cases of coronavirus disease 2019 (COVID-19)-associated leukoencephalopathy have been reported. Although most cases involve hypoxia, the pathophysiological mechanism and neurologic outcomes of COVID-19-associated leukoencephalopathy remain unclear.

Case presentation

We report a case of COVID-19-associated leukoencephalopathy without severe hypoxia in a 65-year-old woman diagnosed with pyelonephritis. After the initiation of intravenous ceftriaxone, her fever resolved, but she developed an altered state of consciousness with abnormal behavior and, subsequently, a relapse fever. She was diagnosed with COVID-19 pneumonia and was intubated. Lung-protective ventilation with deep sedation and neuromuscular blockade were used for treatment. After cessation of sedative administration, her mental status remained at a Glasgow Coma Scale score of 3. COVID-19 was assumed to have caused leukoencephalopathy due to the absence of severe hypoxia or other potential causes. She subsequently showed gradual neurologic improvement. Three months after the COVID-19 diagnosis, she regained alertness, with a Glasgow Coma Scale score of 15.

Conclusion

Clinicians should consider leukoencephalopathy in the differential diagnosis of consciousness disorders in patients with severe COVID-19, even in the absence of severe hypoxia. Gradual neurologic improvement can be expected in such cases.

…

Abstract

Background

Infection with carbapenem-resistant Enterobacterales (CRE) is associated with a high mortality rate in kidney transplant recipients, and colonization with CRE is one of the major risk factors for CRE infection. There is, therefore, a need to improve the capacity to detect colonization with CRE among inpatients.

Methods

In this prospective study, we compared the performance of real-time PCR for carbapenemase directly from rectal swabs with that of conventional CRE surveillance culture in all patients admitted to a kidney transplant ward between February 2019 and March 2020. Surveillance culture and real-time PCR were performed at admission and weekly until hospital discharge. Two perineum-rectal swabs were collected: one for culture and one for PCR.

Results

We collected 905 paired samples for CRE surveillance from 399 patients, of whom 347 (87.0%) were kidney transplant recipients and 52 were waiting list patients. CRE was detected by culture and/or PCR in 75 patients (18.8%). Positivity for CRE was identified by PCR in 62 (15.5%) of the 399 patients and by culture in 55 (13.8%); 20 (5.0%) of the patients tested positive only on PCR, and 13 (3.3%) tested positive only on culture. The most common carbapenemase and species were, respectively, blaKPC (in 85.5%) and Klebsiella pneumoniae (in 80.0%). Infection with CRE occurred in 21.6% of the colonized patients, those cases occurred only among kidney transplant recipients. None of the patients who tested negative on culture developed CRE infection.

Conclusion

In conclusion, the two methods are complementary and could be useful in a scenario of high CRE prevalence.

…

Abstract

Background

Legionella-related community acquired pneumonia (CAP) is a disease with an increasing incidence and a high mortality rate, especially if empirical antibiotic therapy is inadequate. Antibiotic treatment highly relies on clinical symptoms, although proven non-specific, because currently available diagnostic techniques provide insufficient accuracy for detecting Legionella CAP on admission. This study validates a diagnostic scoring system for detection of Legionella-related CAP, based on six items on admission (Legionella prediction score).

Methods

We included patients with Legionella-related CAP admitted to five large Dutch hospitals between 2006 and 2016. Controls were non-Legionella-related CAP patients. The following six conditions were rewarded one point if present: fever > 39.4 °C; dry cough; hyponatremia (sodium) < 133 mmol/L; lactate dehydrogenase (LDH) > 225 mmol/L; C-reactive protein (CRP) > 187 mg/L and platelet count < 171 × 109/L. The accuracy of the prediction score was assessed by calculating the area under the curve (AUC) through logistic regression analysis.

Results

We included 131 cases and 160 controls. A score of 0 occurred in non-Legionella-related CAP patients only, a score of 5 and 6 in Legionella-related CAP patients only. A cut-off ≥ 4 resulted in a sensitivity of 58.8% and a specificity of 93.1%. The AUC was 0.89 (95% CI 0.86–0.93). The strongest predictors were elevated LDH, elevated CRP and hyponatremia.

Conclusions

This multi-centre study validates the Legionella prediction score, an easily applicable diagnostic scoring system, in a large group of patients and finds high diagnostic accuracy. The score shows promise for future prospective validation and could contribute to targeted antibiotic treatment of suspected Legionella CAP.

…

Long term mortality is increased in elderly patients with pneumonia. We aimed to test if residual inflammation is predictive of one-year mortality after pneumonia.

Abstract

Background

Monitoring of antimicrobial resistance (AMR) is of great importance due to the frequency of strains becoming increasingly resistant to antibiotics. This review, using a public health focused approach, which aims to understand and describe the current status of AMR in Morocco in relation to WHO priority pathogens and treatment guidelines.

Methods

PubMed, ScienceDirect and Google Scholar Databases and grey literature are searched published articles on antimicrobial drug resistance data for GLASS priority pathogens isolated from Morocco between January 2011 and December 2021. Articles are screened using strict inclusion/exclusion criteria. AMR data is extracted with medians and IQR of resistance rates.

Results

Forty-nine articles are included in the final analysis. The most reported bacterium is Escherichia coli with median resistance rates of 90.9%, 64.0%, and 56.0%, for amoxicillin, amoxicillin-clavulanic acid, and co-trimoxazole, respectively. Colistin had the lowest median resistance with 0.1%. A median resistance of 63.0% is calculated for amoxicillin-clavulanic acid in Klebsiella pneumonia. Imipenem resistance with a median of 74.5% is reported for Acinetobacter baumannii. AMR data for Streptococcus pneumonie does not exceed 50.0% as a median.

Conclusions

Whilst resistance rates are high for most of GLASS pathogens, there are deficient data to draw vigorous conclusions about the current status AMR in Morocco. The recently join to the GLASS system surveillance will begin to address this data gap.

…

Abstract

Objectives

With modern combination antiretroviral Treatment (cART) a normal life expectancy among people living with HIV (PLWH) has become reality if started early enough prior to the onset of more pronounced immunodeficiency. Therefore, prevention measures against other infectious diseases among this vulnerable group have gained increased attention. Indeed, the EACS guidelines recommend vaccinations against HAV, HBV, HPV, Influenza, Neisseria meningitidis, Streptococcus pneumoniae and VZV in HIV-infected adults.

Methods

All PLWH under cART attending our ID outpatient clinic between April to June 2018, were assessed during consultation for vaccination status regarding pneumococcus, Hepatitis A and B, influenza, varicella, meningococcus and HPV using a pre-defined questionnaire, vaccination certificates and medical records. In addition, the cohort database was screened for Hepatitis A and B serology and HIV surrogate markers.

Results

A total of 305 PLWH (82.3% male, 17.7% female) was included, median age was 48 years (IQR 47–51). Median CD4 + T cell count was 543 (IQR 304–770), and for 297 (97.4%) PLWH CD4 + T cell count was ≥ 200/ul. The viral load was undetectable (< 40 copies/ml) in 289 (94.8%) cases. Highest vaccination rates were observed for HAV (87.4%), Streptococcus pneumoniae (77.4%) and Influenza (76.5%). 64.3% PLWH got vaccinated against HBV, whereas VZV vaccination only played a minor role, in the context of the high rate of cleared infections (99.0%). Lowest vaccination rates were detected for HPV (0%) and Neisseria meningitidis (3.0%).

Conclusions

Our data suggest that vaccination rates among PLWH are higher compared to the general German population. Implementation of EACS guidelines into daily routine though is not fully executed and the need for improving vaccination rates has to be emphasized. Centrally organized vaccination registers as well as electronic medical records could be helpful tools to detect a lack of vaccination coverage and send digital vaccination reminders particularly among risk groups.

…

Abstract

Background

Monitoring of antimicrobial resistance (AMR) is of great importance due to the frequency of strains becoming increasingly resistant to antibiotics. This review, using a public health focused approach, which aims to understand and describe the current status of AMR in Morocco in relation to WHO priority pathogens and treatment guidelines.

Methods

PubMed, ScienceDirect and Google Scholar Databases and grey literature are searched published articles on antimicrobial drug resistance data for GLASS priority pathogens isolated from Morocco between January 2011 and December 2021. Articles are screened using strict inclusion/exclusion criteria. AMR data is extracted with medians and IQR of resistance rates.

Results

Forty-nine articles are included in the final analysis. The most reported bacterium is Escherichia coli with median resistance rates of 90.9%, 64.0%, and 56.0%, for amoxicillin, amoxicillin-clavulanic acid, and co-trimoxazole, respectively. Colistin had the lowest median resistance with 0.1%. A median resistance of 63.0% is calculated for amoxicillin-clavulanic acid in Klebsiella pneumonia. Imipenem resistance with a median of 74.5% is reported for Acinetobacter baumannii. AMR data for Streptococcus pneumonie does not exceed 50.0% as a median.

Conclusions

Whilst resistance rates are high for most of GLASS pathogens, there are deficient data to draw vigorous conclusions about the current status AMR in Morocco. The recently join to the GLASS system surveillance will begin to address this data gap.

…

Abstract

Objectives

With modern combination antiretroviral Treatment (cART) a normal life expectancy among people living with HIV (PLWH) has become reality if started early enough prior to the onset of more pronounced immunodeficiency. Therefore, prevention measures against other infectious diseases among this vulnerable group have gained increased attention. Indeed, the EACS guidelines recommend vaccinations against HAV, HBV, HPV, Influenza, Neisseria meningitidis, Streptococcus pneumoniae and VZV in HIV-infected adults.

Methods

All PLWH under cART attending our ID outpatient clinic between April to June 2018, were assessed during consultation for vaccination status regarding pneumococcus, Hepatitis A and B, influenza, varicella, meningococcus and HPV using a pre-defined questionnaire, vaccination certificates and medical records. In addition, the cohort database was screened for Hepatitis A and B serology and HIV surrogate markers.

Results

A total of 305 PLWH (82.3% male, 17.7% female) was included, median age was 48 years (IQR 47–51). Median CD4 + T cell count was 543 (IQR 304–770), and for 297 (97.4%) PLWH CD4 + T cell count was ≥ 200/ul. The viral load was undetectable (< 40 copies/ml) in 289 (94.8%) cases. Highest vaccination rates were observed for HAV (87.4%), Streptococcus pneumoniae (77.4%) and Influenza (76.5%). 64.3% PLWH got vaccinated against HBV, whereas VZV vaccination only played a minor role, in the context of the high rate of cleared infections (99.0%). Lowest vaccination rates were detected for HPV (0%) and Neisseria meningitidis (3.0%).

Conclusions

Our data suggest that vaccination rates among PLWH are higher compared to the general German population. Implementation of EACS guidelines into daily routine though is not fully executed and the need for improving vaccination rates has to be emphasized. Centrally organized vaccination registers as well as electronic medical records could be helpful tools to detect a lack of vaccination coverage and send digital vaccination reminders particularly among risk groups.

…

: Patients with severe pneumonia admitted to the intensive care unit (ICU) have a high risk of mortality, and the microbiome is likely to affect the outcome of ICU patients with severe pneumonia; however, the skin microbiota in ICU patients with severe pneumonia remains unclear. In this study, based on 16S rRNA sequencing, we explored the difference in skin bacterial richness and diversity between the group of ICU patients with severe pneumonia (PG) and the group of healthy controls (CG).

Introduction

Pneumonia is a leading cause of mortality and a common indication for antibiotic in elderly patients. However, its diagnosis is often inaccurate. We aim to compare the diagnostic accuracy, the clinical and cost outcomes and the use of antibiotics associated with three imaging strategies in patients >65 years old with suspected pneumonia in the emergency room (ER): chest X-ray (CXR, standard of care), low-dose CT scan (LDCT) or lung ultrasonography (LUS).

Methods and analysis

This is a multicentre randomised superiority clinical trial with three parallel arms. Patients will be allocated in the ER to a diagnostic strategy based on either CXR, LDCT or LUS. All three imaging modalities will be performed but the results of two of them will be masked during 5 days to the patients, the physicians in charge of the patients and the investigators according to random allocation. The primary objective is to compare the accuracy of LDCT versus CXR-based strategies. As secondary objectives, antibiotics prescription, clinical and cost outcomes will be compared, and the same analyses repeated to compare the LUS and CXR strategies. The reference diagnosis will be established a posteriori by a panel of experts. Based on a previous study, we expect an improvement of 16% of the accuracy of pneumonia diagnosis using LDCT instead of CXR. Under this assumption, and accounting for 10% of drop-out, the enrolment of 495 patients is needed to prove the superiority of LDCT over CRX (alpha error=0.05, beta error=0.10).

Ethics and dissemination

Ethical approval: CER Geneva 2019-01288.

Trial registration number

NCT04978116.

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Abstract

Background

Etiological diagnosis is a key step in the treatment of patients with rare pulmonary mycosis, and the lack of understanding of this disease and lack of specific markers for the detection of rare species, such as Exophiala dermatitidis, add to the difficulty in diagnosing the condition. Therefore, improving the diagnostic strategies for this disease is very important.

Case presentation

A 52-year-old man presented with cough, sputum production and hemoptysis; chest computed tomography (CT) revealed multiple bilateral lesions. The pathogen was unable to be identified after three biopsies. Subsequently, we performed combined tissue metagenomic next-generation sequencing (mNGS). The results of mNGS and a good therapeutic response helped to identify the causative pathogen as Exophiala dermatitidis. Finally, the patient was diagnosed with Exophiala dermatitidis pneumonia.

Conclusions

Combining molecular techniques, such as mNGS, with clinical microbiological tests will improve the rate of positivity in the diagnosis of rare fungal infections, and the importance of follow-up should be emphasized.

…

Abstract

Background

The management of febrile illnesses is challenging in settings where diagnostic laboratory facilities are limited, and there are few published longitudinal data on children presenting with fever in such settings. We have previously conducted the first comprehensive study of infectious aetiologies of febrile children presenting to a tertiary care facility in Ethiopia. We now report on clinicians’ prescribing adherence with guidelines and outcomes of management in this cohort.

Methods

We consecutively enrolled febrile children aged 2 months and under 13 years, who were then managed by clinicians based on presentation and available laboratory and radiologic findings on day of enrolment. We prospectively collected outcome data on days 7 and 14, and retrospectively evaluated prescribing adherence with national clinical management guidelines.

Results

Of 433 children enrolled, the most common presenting syndromes were pneumonia and acute diarrhoea, diagnosed in 177 (40.9%) and 82 (18.9%), respectively. Antibacterial agents were prescribed to 360 (84.7%) of 425 children, including 36 (34.0%) of 106 children without an initial indication for antibacterials according to guidelines. Antimalarial drugs were prescribed to 47 (11.1%) of 425 children, including 30 (7.3%) of 411 children with negative malaria microscopy. Fever had resolved in 357 (89.7%) of 398 children assessed at day 7, and in-hospital death within 7 days occurred in 9 (5.9%) of 153 admitted patients. Among children with pneumonia, independent predictors of persisting fever or death by 7 days were young age and underweight for age. Antibacterial prescribing in the absence of a guideline-specified indication (overprescribing) was more likely among infants and those without tachypnea, while overprescribing antimalarials was associated with older age, anaemia, absence of cough, and higher fevers.

Conclusion

Our study underscores the need for improving diagnostic support to properly guide management decisions and enhance adherence by clinicians to treatment guidelines.

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Abstract

Background

Atypical pathogens (AP), present in some patients with community-acquired pneumonia (CAP), are intrinsically resistant to betalactam drugs, the mainstay of empirical antibiotic treatment. Adding antibiotic coverage for AP increases the risk of adverse effects and antimicrobial selection pressure, while withholding such coverage may worsen the prognosis if an AP is causative. A clinical model predicting the presence of AP would allow targeting atypical coverage for patients most likely to benefit.

Methods

This is a secondary analysis of a multicentric randomized controlled trial that included 580 adults patients hospitalized for CAP. A predictive score was built using independent predictive factors for AP identified through multivariate analysis. Accuracy of the score was assessed using area under the receiver operating curve (AUROC), sensitivity, and specificity.

Results

Prevalence of AP was 5.3%. Age < 75 years (OR 2.7, 95% CI 1.2–6.2), heart failure (OR 2.6, 95% CI 1.1–6.1), absence of chest pain (OR 3.0, 95% CI 1.1–8.2), natremia < 135 mmol/L (OR 3.0, 95% CI 1.4–6.6) and contracting the disease in autumn (OR 2.7, 95% CI 1.3–5.9) were independently associated with AP. A predictive score using these factors had an AUROC of 0.78 (95% CI 0.71–0.85). A score of 0 or 1 (present in 33% of patients) had 100% sensitivity and 35% specificity.

Conclusion

Use of a score built on easily obtained clinical and laboratory data would allow safe withholding of atypical antibiotic coverage in a significant number of patients, with an expected positive impact on bacterial resistance and drug adverse effects.

Trial registration: NCT00818610.

…

Journal of Medical Virology, Accepted Article.

Abstract

Background

Etiological diagnosis is a key step in the treatment of patients with rare pulmonary mycosis, and the lack of understanding of this disease and lack of specific markers for the detection of rare species, such as Exophiala dermatitidis, add to the difficulty in diagnosing the condition. Therefore, improving the diagnostic strategies for this disease is very important.

Case presentation

A 52-year-old man presented with cough, sputum production and hemoptysis; chest computed tomography (CT) revealed multiple bilateral lesions. The pathogen was unable to be identified after three biopsies. Subsequently, we performed combined tissue metagenomic next-generation sequencing (mNGS). The results of mNGS and a good therapeutic response helped to identify the causative pathogen as Exophiala dermatitidis. Finally, the patient was diagnosed with Exophiala dermatitidis pneumonia.

Conclusions

Combining molecular techniques, such as mNGS, with clinical microbiological tests will improve the rate of positivity in the diagnosis of rare fungal infections, and the importance of follow-up should be emphasized.

…

Abstract

Background

The management of febrile illnesses is challenging in settings where diagnostic laboratory facilities are limited, and there are few published longitudinal data on children presenting with fever in such settings. We have previously conducted the first comprehensive study of infectious aetiologies of febrile children presenting to a tertiary care facility in Ethiopia. We now report on clinicians’ prescribing adherence with guidelines and outcomes of management in this cohort.

Methods

We consecutively enrolled febrile children aged 2 months and under 13 years, who were then managed by clinicians based on presentation and available laboratory and radiologic findings on day of enrolment. We prospectively collected outcome data on days 7 and 14, and retrospectively evaluated prescribing adherence with national clinical management guidelines.

Results

Of 433 children enrolled, the most common presenting syndromes were pneumonia and acute diarrhoea, diagnosed in 177 (40.9%) and 82 (18.9%), respectively. Antibacterial agents were prescribed to 360 (84.7%) of 425 children, including 36 (34.0%) of 106 children without an initial indication for antibacterials according to guidelines. Antimalarial drugs were prescribed to 47 (11.1%) of 425 children, including 30 (7.3%) of 411 children with negative malaria microscopy. Fever had resolved in 357 (89.7%) of 398 children assessed at day 7, and in-hospital death within 7 days occurred in 9 (5.9%) of 153 admitted patients. Among children with pneumonia, independent predictors of persisting fever or death by 7 days were young age and underweight for age. Antibacterial prescribing in the absence of a guideline-specified indication (overprescribing) was more likely among infants and those without tachypnea, while overprescribing antimalarials was associated with older age, anaemia, absence of cough, and higher fevers.

Conclusion

Our study underscores the need for improving diagnostic support to properly guide management decisions and enhance adherence by clinicians to treatment guidelines.

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by Maxime Léger, Denis Frasca, Antoine Roquilly, Philippe Seguin, Raphaël Cinotti, Claire Dahyot-Fizelier, Karim Asehnoune, Florent Le Borgne, Thomas Gaillard, Yohann Foucher, Sigismond Lasocki, for AtlanRéa group

Barbiturates are proposed as a second/third line treatment for intracranial hypertension in traumatic brain injury (TBI) patients, but the literature remains uncertain regarding their benefit/risk balance. We aimed to evaluate the impact of barbiturates therapy in TBI patients with early intracranial hypertension on the intensive care unit (ICU) survival, the occurrence of ventilator-associated pneumonia (VAP), and the patient’s functional status at three months. We used the French AtlanREA prospective cohort of trauma patients. Using a propensity score-based methodology (inverse probability of treatment weighting), we compared patients having received barbiturates within the first 24 hours of admission (barbiturates group) and those who did not (control group). We used cause-specific Cox models for ICU survival and risk of VAP, and logistic regression for the 3-month Glasgow Outcome Scale (GOS) evaluation. Among the 1396 patients with severe trauma, 383 had intracranial hypertension on admission and were analyzed. Among them, 96 (25.1%) received barbiturates. The early use of barbiturates was significantly associated with increased ICU mortality (HR = 1.85, 95%CI 1.03–3.33). However, barbiturates treatment was not significantly associated with VAP (HR = 1.02, 95%CI 0.75–1.41) or 3-month GOS (OR = 1.67, 95%CI 0.84–3.33). Regarding the absence of relevant clinical trials, our results suggest that each early prescription of barbiturates requires a careful assessment of the benefit/risk ratio.

by Michael Bakker, Michaela E. Johnson, Lauren Corre, Deanna N. Mill, Xingzhuo Li, Richard J. Woodman, Jacinta L. Johnson

Background Admission to hospital introduces risks for people with Parkinson’s disease in maintaining continuity of their highly individualized medication regimens, which increases their risk of medication errors. This is of particular concern as omitted medications and irregular dosing can cause an immediate increase in an individual’s symptoms as well as other adverse outcomes such as swallowing difficulties, aspiration pneumonia, frozen gait and even potentially fatal neuroleptic malignant type syndrome. Objective To determine the occurrence and identify factors that contribute to Parkinson’s medication errors in Australian hospitals. Methods A retrospective discharge diagnosis code search identified all admissions for people with Parkinson’s disease to three tertiary metropolitan hospitals in South Australia, Australia over a 3-year period. Of the 405 case notes reviewed 351 admissions met our inclusion criteria. Results Medication prescribing (30.5%) and administration (85%) errors during admission were extremely common, with the most frequent errors related to administration of levodopa preparations (83%). A higher levodopa equivalent dosage, patients with a modified swallowing status or nil by mouth order during admission, and patients who did not have a pharmacist led medication history within 24 hours of admission had significantly higher rates of medication errors. Conclusions This study identified 3 major independent factors that increased the risk of errors during medication management for people with Parkinson’s disease during hospitalization. Thus, targeting these areas for preventative interventions have the greatest chance of producing a clinically meaningful impact on the number of hospital medication errors occurring in the Parkinson’s population.…

by Eman Zeyad I. Elmekaty, Rim Alibrahim, Rania Hassanin, Sitelbanat Eltaib, Ahmed Elsayed, Fatima Rustom, Mohamed Izham Mohamed Ibrahim, Mohammed Abu Khattab, Hussam Al Soub, Muna Al Maslamani, Abdullatif Al-Khal

Background Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. Methods and findings This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients’ electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3–7] vs. 6.5 days [IQR 4–12]; HR 1.345 [95%CI: 1.070–1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3–8] vs. 8 days [IQR 4–13]; HR 1.520 (95%CI: 1.2–1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15–33] vs. 21 days [IQR 12.8–30]; HR 0.772 (95%CI: 0.607–0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. Conclusion In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings. Trial registration ClinicalTrials.gov number, NCT04425382.…

Journal Name: The American Journal of Tropical Medicine and HygieneVolume: 106Issue: 5Pages: 1560-1560

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Abstract

Background

Atypical pathogens (AP), present in some patients with community-acquired pneumonia (CAP), are intrinsically resistant to betalactam drugs, the mainstay of empirical antibiotic treatment. Adding antibiotic coverage for AP increases the risk of adverse effects and antimicrobial selection pressure, while withholding such coverage may worsen the prognosis if an AP is causative. A clinical model predicting the presence of AP would allow targeting atypical coverage for patients most likely to benefit.

Methods

This is a secondary analysis of a multicentric randomized controlled trial that included 580 adults patients hospitalized for CAP. A predictive score was built using independent predictive factors for AP identified through multivariate analysis. Accuracy of the score was assessed using area under the receiver operating curve (AUROC), sensitivity, and specificity.

Results

Prevalence of AP was 5.3%. Age < 75 years (OR 2.7, 95% CI 1.2–6.2), heart failure (OR 2.6, 95% CI 1.1–6.1), absence of chest pain (OR 3.0, 95% CI 1.1–8.2), natremia < 135 mmol/L (OR 3.0, 95% CI 1.4–6.6) and contracting the disease in autumn (OR 2.7, 95% CI 1.3–5.9) were independently associated with AP. A predictive score using these factors had an AUROC of 0.78 (95% CI 0.71–0.85). A score of 0 or 1 (present in 33% of patients) had 100% sensitivity and 35% specificity.

Conclusion

Use of a score built on easily obtained clinical and laboratory data would allow safe withholding of atypical antibiotic coverage in a significant number of patients, with an expected positive impact on bacterial resistance and drug adverse effects.

Trial registration: NCT00818610.

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Journal of Medical Virology, Accepted Article.

Infection and Immunity, Ahead of Print. …

Objectives

Coagulation changes associated with COVID-19 suggest the presence of a hypercoagulable state with pulmonary microthrombosis and thromboembolic complications. We assessed the dynamic association of COVID-19-related coagulation abnormalities with respiratory failure and mortality.

Design

Single-centre, prospective cohort study with descriptive analysis and logistic regression.

Setting

Tertiary care hospital, North India.

Participants

Patients with COVID-19 pneumonia requiring intensive care unit (ICU) admission between August 2020 and November 2020.

Primary and secondary outcome measures

We compared the coagulation abnormalities using standard coagulation tests like prothrombin time, D-dimer, platelet count, etc and point-of-care global coagulation test, Sonoclot (glass beaded(gb) and heparinase-treated(h)). Incidence of thromboembolic or bleeding events and presence of endogenous heparinoids were assessed. Cox proportional Hazards test was used to assess the predictors of 28-day mortality.

Measurement

All patients underwent Sonoclot (glass beaded) test at admission apart from the routine investigations. In patients at risk of thromboembolic or bleeding phenomena, paired tests were performed at day 1 and 3 with Sonoclot. Activated clotting time (ACT) <110 s and peak amplitude >75 units were used as the cut-off for hypercoagulable state. Presence of heparin-like effect (HLE) was defined by a correction of ACT ≥40 s in h-Sonoclot.

Results

Of 215 patients admitted to ICU, we included 74 treatment naive subjects. A procoagulant profile was seen in 45.5% (n=5), 32.4% (n=11) and 20.7% (n=6) in low-flow, high-flow and invasive ventilation groups. Paired Sonoclot assays in a subgroup of 33 patients demonstrated the presence of HLE in 17 (51.5%) and 20 (62.5%) at day 1 and 3, respectively. HLE (day 1) was noted in 59% of those who bled during the disease course. Mortality was observed only in the invasive ventilation group (16, 55.2%) with overall mortality of 21.6%. HLE predicted the need for mechanical ventilation (HR 1.2 CI 1.04 to 1.4 p=0.00). On multivariate analysis, the presence of HLE (HR 1.01; CI 1.006 to 1.030; p=0.025), increased C reactive protein (HR 1.040; CI 1.020 to 1.090; p=0.014), decreased platelet function (HR 0.901; CI 0.702 to 1.100 p=0.045) predicted mortality at 28days.

Conclusion

HLE contributed to hypocoagulable effect and associated with the need for invasive ventilation and mortality in patients with severe COVID-19 pneumonia.

Trial registration

NCT04668404; ClinicalTrials.gov.in. Available from https://clinicaltrials.gov/ct2/show/NCT04668404.

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Introduction

The aim of this evaluation is to understand whether introducing stabilisation rooms equipped with pulse oximetry and oxygen systems to frontline health facilities in Ikorodu, Lagos State, alongside healthcare worker (HCW) training improves the quality of care for children with pneumonia aged 0–59 months. We will explore to what extent, how, for whom and in what contexts the intervention works.

Methods and analysis

Quasi-experimental time-series impact evaluation with embedded mixed-methods process and economic evaluation. Setting: seven government primary care facilities, seven private health facilities, two government secondary care facilities. Target population: children aged 0–59 months with clinically diagnosed pneumonia and/or suspected or confirmed COVID-19. Intervention: ‘stabilisation rooms’ within participating primary care facilities in Ikorodu local government area, designed to allow for short-term oxygen delivery for children with hypoxaemia prior to transfer to hospital, alongside HCW training on integrated management of childhood illness, pulse oximetry and oxygen therapy, immunisation and nutrition. Secondary facilities will also receive training and equipment for oxygen and pulse oximetry to ensure minimum standard of care is available for referred children. Primary outcome: correct management of hypoxaemic pneumonia including administration of oxygen therapy, referral and presentation to hospital. Secondary outcome: 14-day pneumonia case fatality rate. Evaluation period: August 2020 to September 2022.

Ethics and dissemination

Ethical approval from University of Ibadan, Lagos State and University College London. Ongoing engagement with government and other key stakeholders during the project. Local dissemination events will be held with the State Ministry of Health at the end of the project (December 2022). We will publish the main impact results, process evaluation and economic evaluation results as open-access academic publications in international journals.

Trial registration number

ACTRN12621001071819; Registered on the Australian and New Zealand Clinical Trials Registry.

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Abstract

Background

To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in immunocompromised patients for the diagnosis of suspected pneumonia in comparison with that of conventional microbiological tests (CMTs).

Methods

Sixty-nine immunocompromised patients with suspected pneumonia received both CMTs and mNGS of BALF were analyzed retrospectively. The diagnostic value was compared between CMTs and mNGS, using the clinical composite diagnosis as the reference standard.

Results

Sixty patients were diagnosed of pneumonia including fifty-two patients with identified pathogens and eight patients with probable pathogens. Taking the composite reference standard as a gold standard, 42 pathogens were identified by CMTs including nine bacteria, 17 fungi, 8 virus, 6 Mycobacterium Tuberculosis, and two Legionella and 19(45%) of which were detected by BALF culture. As for mNGS, it identified 76 pathogens including 20 bacteria, 31 fungi, 14 virus, 5 Mycobacterium Tuberculosis, four Legionella and two Chlamydia psittaci. The overall detection rate of mNGS for pathogens were higher than that of CMTs. However, a comparable diagnostic accuracy of mNGS and CMTs were found for bacterial and viral infections. mNGS exhibited a higher diagnostic accuracy for fungal detection than CMTs (78% vs. 57%, P < 0.05), which mainly because of the high sensitivity of mNGS in patients with Pneumocystis jirovecii pneumonia (PJP) (100% vs. 28%, P < 0.05). Nineteen patients were identified as pulmonary co-infection, mNGS test showed a higher detection rate and broader spectrum for pathogen detection than that of CMTs in co-infection. Moreover, Pneumocystis jirovecii was the most common pathogen in co-infection and mNGS have identified much more co-pathogens of PJP than CMTs.

Conclusions

mNGS of BALF improved the microbial detection rate of pathogens and exhibited remarkable advantages in detecting PJP and identifying co-infection in immunocompromised patients.

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Abstract

Background

We report a case of spine infection with mucormycosis that manifested signs of paraplegia in a patient suffering from disseminated mucormycosis. Timely and effective surgery was performed. A review of the literature is included.

Case presentation

A patient with diabetic ketoacidosis complained of back pain and fatigue for one month, and his right lower extremity activity had been limited for 10 days. T4–T6 vertebral and paravertebral soft tissue-involved infections were identified by MRI, which were derived from right lung pneumonia. He underwent abscess debridement, spinal canal decompression, pedicle screw fixation and amphotericin B liposome injection. Histopathological examination revealed broad aseptate hyphae suggestive of invasive mucormycosis. There was improvement in neurological function after surgical and medical treatment. Three months after the surgery, the patient died of uncontrollable massive bleeding of the urinary system. Mucormycosis is characterized by rapid development and a high mortality rate. This case shows the significance of a multidisciplinary team in the diagnosis and treatment of patients with mucormycosis. In addition, orthopedic surgeons should design appropriate surgery plans for spine-involved mucormycosis patients.

Conclusion

This case present a patient with paraplegia caused by the spread of pulmonary mucormycosis to the vertebral and paravertebral soft tissue of levels T4–T6. After medical treatment, surgical debridement and internal fixation, the patient recovered well but later patient died of possible disease dissemination to the renal or urinary tract which resulted in massive haemorrhage.

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Introduction

Congenital heart disease (CHD) comprises the anatomic malformations that jeopardise the structure and function of the heart. It can be extremely complex and serious, corresponding to 30% of all deaths in the first month of life. The surgical approach for adequate treatment requires postoperative mechanical ventilation. The most critical decision related to the postoperative management of patients submitted to cardiac surgery is the right time for extubation, especially because not only abrupt or inadequate discontinuation of ventilatory support can lead to clinical decline and necessity of reintubation but also extended time of mechanical ventilation, which can lead to complications, such as pneumonia, atelectasis, diaphragm hypertrophy, and increasing morbidity and mortality.

Methods and analysis

This systematic review plans to include individual parallel, cross-over and cluster randomised controlled trials regarding any breathing trial test to predict extubation success in children submitted to cardiac surgery due to CHD. Studies with paediatric patients submitted to cardiac surgery for congenital cardiopathy repair, attended at a critical care unit, and under mechanical ventilatory support will be included. The main outcomes analysed will be success of extubation, reduction of pulmonary complications and time reduction of mechanical ventilation.

Ethics and dissemination

We will not treat patients directly; therefore, ethics committee approval was not necessary because it is not a primary study. We expect that this study may improve healthcare and medical assistance, helping healthcare professionals with routine daily decisions regarding the correct time for extubation.

PROSPERO registration number

CRD42021223999.

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Abstract

Background

To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in immunocompromised patients for the diagnosis of suspected pneumonia in comparison with that of conventional microbiological tests (CMTs).

Methods

Sixty-nine immunocompromised patients with suspected pneumonia received both CMTs and mNGS of BALF were analyzed retrospectively. The diagnostic value was compared between CMTs and mNGS, using the clinical composite diagnosis as the reference standard.

Results

Sixty patients were diagnosed of pneumonia including fifty-two patients with identified pathogens and eight patients with probable pathogens. Taking the composite reference standard as a gold standard, 42 pathogens were identified by CMTs including nine bacteria, 17 fungi, 8 virus, 6 Mycobacterium Tuberculosis, and two Legionella and 19(45%) of which were detected by BALF culture. As for mNGS, it identified 76 pathogens including 20 bacteria, 31 fungi, 14 virus, 5 Mycobacterium Tuberculosis, four Legionella and two Chlamydia psittaci. The overall detection rate of mNGS for pathogens were higher than that of CMTs. However, a comparable diagnostic accuracy of mNGS and CMTs were found for bacterial and viral infections. mNGS exhibited a higher diagnostic accuracy for fungal detection than CMTs (78% vs. 57%, P < 0.05), which mainly because of the high sensitivity of mNGS in patients with Pneumocystis jirovecii pneumonia (PJP) (100% vs. 28%, P < 0.05). Nineteen patients were identified as pulmonary co-infection, mNGS test showed a higher detection rate and broader spectrum for pathogen detection than that of CMTs in co-infection. Moreover, Pneumocystis jirovecii was the most common pathogen in co-infection and mNGS have identified much more co-pathogens of PJP than CMTs.

Conclusions

mNGS of BALF improved the microbial detection rate of pathogens and exhibited remarkable advantages in detecting PJP and identifying co-infection in immunocompromised patients.

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American Journal of Respiratory and Critical Care Medicine, Volume 205, Issue 9, Page 1116-1118, May 1, 2022. …

Chronic obstructive pulmonary disease (COPD) is estimated to affect more than 350 million people globally and is responsible for 3·2 million deaths per year, making it the third leading cause of mortality worldwide.1 Beyond its direct impact in terms of human suffering, COPD contributes as a comorbidity to other leading causes of mortality, including COVID-19, pneumonia, cardiovascular diseases, stroke, and lung cancer, increasing the risk of these conditions and associated mortality by two to four times.

by Tewachew Awoke, Brhanu Teka, Abraham Aseffa, Shemse Sebre, Aminu Seman, Biruk Yeshitela, Tamrat Abebe, Adane Mihret

Background Infections caused by Klebsiella pneumoniae have been difficult to control because of the worldwide emergence of carbapenem-resistant isolates mainly due to carbapenemase production. Information regarding carbapenemase-producing K. pneumoniae is still scarce in Ethiopia. Therefore, the current study aimed to determine the prevalence of carbapenemase-producing K. pneumoniae and to assess the occurrence of blaNDM and blaKPC carbapenemase genes. Methods A cross-sectional study was conducted from September 2018 to February 2019 at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. A total of 132 non-duplicate K. pneumoniae isolates were studied. Phenotypic confirmation of carbapenemase production was done by modified Carbapenem Inactivation Method (mCIM). Multiplex PCR was performed for the detection of carbapenemase-encoding genes blaKPC, and blaNDM. Results Out of the total 132 K. pneumoniae isolates, 39 (29.6%) were non-susceptible to one or more carbapenems. The prevalence of carbapenemase-producing isolates from the total was 28 (21.2%) with mCIM of which the most dominant gene was blaNDM 26 (92.9%) and one isolate carried blaKPC concomitantly. Carbapenemase-producing K. pneumoniae isolates were 100% non-susceptible to half of the antimicrobials used in the study, including meropenem and ertapenem. Previous use of carbapenems was associated with carbapenemase production (P = 0.004). Conclusions The prevalence of carbapenemase-producing K. pneumoniae isolates was worrying in the study area. To our knowledge, the study described the emergence of blaNDM and blaKPC gene carrying K. pneumoniae in Ethiopia for the first time. Further large-scale molecular-based studies, including other carbapenemase genes and sequencing of K. pneumoniae, are warranted to have a clear awareness about the presence of antimicrobial resistance high-risk clones in Ethiopia.…

Objective

Pneumonia is the single-leading cause of infectious disease deaths in children under-5. Despite this challenge, the utilisation of preventive and curative child health services remains low in Ethiopia. We investigated the association between health post service readiness and caregivers’ awareness of pneumonia services, care-seeking and utilisation of pneumonia-relevant immunisation in four Ethiopian regions.

Design and setting

This cross-sectional study was conducted in 52 districts of four regions of Ethiopia from December 2018 to February 2019. The health posts preparedness for sick child care was assessed using the WHO Health Service Availability and Readiness Assessment tool. Multilevel analyses were employed to examine the associations between health post readiness and household-level awareness and utilisation of services.

Participants

We included 165 health posts, 274 health extension workers (community health workers) and 4729 caregivers with 5787 children 2–59 months.

Outcome measures

Awareness of pneumonia treatment, care-seeking behaviour and coverage of pentavalent-3 immunisation.

Results

Only 62.8% of health posts were ready to provide sick child care services. One-quarter of caregivers were aware of pneumonia services, and 56.8% sought an appropriate care provider for suspected pneumonia. Nearly half (49.3%) of children (12–23 months) had received pentavalent-3 immunisation. General health post readiness was not associated with caregivers’ awareness of pneumonia treatment (adjusted OR, AOR 0.9, 95% CI 0.7 to 1.1) and utilisation of pentavalent-3 immunisation (AOR=1.2, 95% CI 0.8 to 1.6), but negatively associated with care-seeking for childhood illnesses (AOR=0.6, 95% CI 0.4 to 0.8).

Conclusion

We found no association between facility readiness and awareness or utilisation of child health services. There were significant deficiencies in health post preparedness for services. Caregivers had low awareness and utilisation of pneumonia-related services. The results underline the importance of enhancing facility preparedness, providing high-quality care and intensifying demand generation efforts to prevent and treat pneumonia.

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by Luca G. Valente, Ngoc Dung Le, Melissa Pitton, Gabriele Chiffi, Denis Grandgirard, Stephan M. Jakob, David R. Cameron, Grégory Resch, Yok-Ai Que, Stephen L. Leib

Background Treatment failure in pneumococcal meningitis due to antibiotic resistance is an increasing clinical challenge and alternatives to antibiotics warrant investigation. Phage-derived endolysins efficiently kill gram-positive bacteria including multi-drug resistant strains, making them attractive therapeutic candidates. The current study assessed the therapeutic potential of the novel endolysin PlyAZ3aT in an infant rat model of ceftriaxone-resistant pneumococcal meningitis. Methods Efficacy of PlyAZ3aT was assessed in a randomized, blinded and controlled experimental study in infant Wistar rats. Meningitis was induced by intracisternal infection with 5 x 107 CFU/ml of a ceftriaxone-resistant clinical strain of S. pneumoniae, serotype 19A. Seventeen hours post infection (hpi), animals were randomized into 3 treatment groups and received either (i) placebo (phosphate buffered saline [PBS], n = 8), (ii) 50 mg/kg vancomycin (n = 10) or (iii) 400 mg/kg PlyAZ3aT (n = 8) via intraperitoneal injection. Treatments were repeated after 12 h. Survival at 42 hpi was the primary outcome; bacterial loads in cerebrospinal fluid (CSF) and blood were secondary outcomes. Additionally, pharmacokinetics of PlyAZ3aT in serum and CSF was assessed. Results PlyAZ3aT did not improve survival compared to PBS, while survival for vancomycin treated animals was 70% which is a significant improvement when compared to PBS or PlyAZ3aT (p<0.05 each). PlyAZ3aT was not able to control the infection, reflected by the inability to reduce bacterial loads in the CSF, whereas Vancomycin sterilized the CSF and within 25 h. Pharmacokinetic studies indicated that PlyAZ3aT did not cross the blood brain barrier (BBB). In support, PlyAZ3aT showed a peak concentration of 785 μg/ml in serum 2 h after intraperitoneal injection but could not be detected in CSF. Conclusion In experimental pneumococcal meningitis, PlyAZ3aT failed to cure the infection due to an inability to reach the CSF. Optimization of the galenic formulation e.g. using liposomes might enable crossing of the BBB and improve treatment efficacy.…

Antimicrobial Agents and Chemotherapy, Ahead of Print. …

Abstract

Background

We report a case of spine infection with mucormycosis that manifested signs of paraplegia in a patient suffering from disseminated mucormycosis. Timely and effective surgery was performed. A review of the literature is included.

Case presentation

A patient with diabetic ketoacidosis complained of back pain and fatigue for one month, and his right lower extremity activity had been limited for 10 days. T4–T6 vertebral and paravertebral soft tissue-involved infections were identified by MRI, which were derived from right lung pneumonia. He underwent abscess debridement, spinal canal decompression, pedicle screw fixation and amphotericin B liposome injection. Histopathological examination revealed broad aseptate hyphae suggestive of invasive mucormycosis. There was improvement in neurological function after surgical and medical treatment. Three months after the surgery, the patient died of uncontrollable massive bleeding of the urinary system. Mucormycosis is characterized by rapid development and a high mortality rate. This case shows the significance of a multidisciplinary team in the diagnosis and treatment of patients with mucormycosis. In addition, orthopedic surgeons should design appropriate surgery plans for spine-involved mucormycosis patients.

Conclusion

This case present a patient with paraplegia caused by the spread of pulmonary mucormycosis to the vertebral and paravertebral soft tissue of levels T4–T6. After medical treatment, surgical debridement and internal fixation, the patient recovered well but later patient died of possible disease dissemination to the renal or urinary tract which resulted in massive haemorrhage.

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