Treatment failure in clinically stable CAP patients associated with male gender and age

20th October 2021

Treatment failure in clinically stable CAP patients after 15 days is significantly associated with only male gender and age.

Treatment failure in patients with community-acquired pneumonia (CAP) who are deemed clinically stable is associated with being male and age, according to a study by a team from the Infectious Disease Unit, Raymond-Poincare University Hospital, Paris, France. Treatment failure rates in CAP have been found to range between 2.4 and 31% among hospitalised patients and it is a serious complication that is associated with high morbidity and mortality rates. Nevertheless, once CAP patients achieve clinical stability, deterioration is much less likely as witnessed by a study of nearly 700 adults hospitalised with CAP which found that  less than 1% worsened once stable.

Shorter antibiotic treatment courses for those hospitalised with CAP have the potential to reduce antibiotic resistance, adverse events and related costs. In a recent trial, the Paris team undertook a double-blind, randomised, placebo-controlled trial, the Pneumonia Short Treatment (PTC), among adult patients admitted to hospital with moderately severe CAP. The purpose of the trial was to determine whether there was a need for an additional 5-day course of β-lactam antibiotic treatment in CAP patients who were clinically stable after 3 days of treatment. The study’s primary outcome was cure, 15 days after the first antibiotic intake, defined by apyrexia, resolution or improvement of respiratory symptoms and no additional antibiotic treatment for any cause. The results showed that discontinuing β-lactam treatment after 3 days was non-inferior to 8 days of treatment.

For their latest study, the team performed a secondary analysis of data from the PTC trial to examine the factors associated with treatment failure. Details of the patient population, outcome measures etc were provided in the PTC study publication.

Findings

The PTC trial included 310 patient and the secondary analysis comprised 291 of these patients with a mean age of 69.6 years (59.8% male). The overall treatment failure rate was 26.8% (78 patients) and mainly due to a lack of symptom resolution (79.5%), including purulent sputum. dyspnoea and cough. Other causes of treatment failure were the need for additional antibiotics (10.2%) and fever at day 15 (5.1%).

Multivariate analysis revealed that male gender was significantly associated with treatment failure (odds ratio, OR = 1.92, 95% CI 1.08 – 3.49, p = 0.03) as was age (OR = 1.02, 95% CI 1.0 – 1.05, p = 0.03). This latter result was not surprising given that the mean age of those in the failure group was 76.2 years compared to 67.2 years in the cure group (p = 0.01). Interestingly, as noted in the original PTC study, the duration of antibiotic therapy had no impact on treatment failure.

The authors concluded that among clinically stable patients with CAP who received a 3-day course of antibiotics, only age and male gender, not disease severity or co-morbidities, were significantly associated with treatment failure. They suggested that these results should be taken into account in the treatment of those with CAP.

Citation

Dinh A et al.Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia. A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open 2021

Guideline discordant antibiotic prescribing for ED patients with severe CAP increases mortality

7th October 2021

The presence of guideline discordant antibiotic prescribing for ED patients with severe CAP has been found to increase 30-day mortality.

Community-acquired pneumonia (CAP) is an infection acquired in the community, i.e., outside of a hospital setting. The worldwide incidence of community-acquired pneumonia has been estimated to vary between 1.5 to 14 cases per 1000 person-years. Mortality rates for CAP are very low (< 2%) for patients treated in the community but increase among those hospitalised (5 – 20%) and are higher still (up to 50%) for patients who are admitted to intensive care. Treatment of CAP involves the use of empirical antibiotics and several guidelines exist for the management of CAP. Moreover, evidence suggests that guideline-concordant prescribing for CAP is associated with improved health outcomes and lower resource use in adults. But to what extent would guideline discordant antibiotic prescribing impact on health outcomes and mortality?

This was the question posed by a team from the Department of Emergency Medicine, Seoul National University Bundang Hospital, Republic of Korea. The team undertook a retrospective analysis of adult patients with severe CAP, hospitalised in the emergency department (ED) after the diagnosis of severe CAP, defined by the 2007, Infectious Diseases Society of America/American Thoracic Society guidelines. For the treatment of severe CAP, the guidelines recommend a beta-lactam antibiotic plus either a macrolide or fluoroquinolone. Among penicillin allergic patients, a respiratory fluoroquinolone plus aztreonam is recommended. Data on prescribing , together with demographic and co-morbidity information were obtained from hospital medical records. Patients were then categorised as either being prescribed guideline concordant antibiotics or guideline discordant antibiotics. Propensity score matching was used to reduce selection bias and 30-day survival was estimated with logistic regression.

Findings

A total of 630 patients were included, of whom 179 (28.4%) died within 30 days of being hospitalised. After propensity matching, a total of 255 individuals were included in each group with an approximate age of 75 years (66% male). After propensity matching, guideline discordant prescribing was significantly associated with 30-day mortality (hazard ratio, HR = 1.43, 95% CI 1.05 – 1.93, p = 0.022). In addition, 30-day mortality was found to be lower in the guideline concordant group (23.9% vs 33.3%, concordant vs discordant, p = 0.024).

Commenting on these findings, the authors noted that 43% of patients were prescribed guideline discordant antibiotics for severe CAP and concluded that this was independently associated with 30-day survival.

Citation

Hyun KS et al. Antibiotic prescription consistent with guidelines in emergency department is associated with 30-day survival in severe community-acquired pneumonia. BMC Emerg Med 2021.

Procalcitonin levels unable to distinguish between viral and bacterial community-acquired pneumonia

13th September 2021

The use of procalcitonin levels in an emergency department is unable to distinguish between viral and bacterial community-acquired pneumonia.

Symptoms of community-acquired pneumonia (CAP) include shortness of breath, coughing, fever and chest pain some of which such as fever and coughing, overlap with COVID-19. Determining whether the causative agent in CAP is bacterial or viral can be difficult and measurement of procalcitonin levels can serve as an important biomarker for the presence of a bacterial cause. Given that higher procalcitonin levels are more likely to indicate a bacterial rather than viral cause for CAP, a team from the Emergency Department, University Libre Bruxelles, Belgium, wondered if the measurement of procalcitonin levels could help distinguish between viral and bacterial CAP in patients infected with COVID-19 and retrospectively analysed data for a cohort of patients admitted to their emergency department.

All patients who were admitted with a suspicion of CAP had their procalcitonin levels measured. Subsequently, enrolled patients were those with clinical signs of a lower respiratory tract infection and with at least one symptom of acute respiratory illness, e.g., cough, dyspnoea, sputum production, tachypnoea and pleuritic chest pain. Other inclusion criteria were those with signs of an acute infection, e.g., temperature > 38oC, chills, altered mental status and a leucocyte count > 10,000/microL and oxygen saturation < 94%. Only patients who underwent both bacteriological, viral and radiological imaging (CT) within 48 hours of admission were subsequently included. Patients were classified as having bacterial CAP based on both microbiological analysis and the findings from the CT scan. Alternatively, patients were classed as having viral CAP in the absence of positive bacteriological findings and where the CT scan indicated a high suspicion of viral pneumonia.

Findings
During the period of the study, 3593 patients visited the emergency department with symptoms potentially related to COVID-19 and 151 were subsequently included in the analysis after applying the inclusion criteria, of whom, 138 had a microbiologically confirmed bacterial pathogen. Among those with diagnosed viral CAP, 112 had COVID-19-related pneumonia. The discriminatory accuracy of procalcitonin levels for bacterial and viral CAP were calculated from receiver operating characteristic (ROC) curves. The median procalcitonin levels were higher in bacterial CAP (0.53ng/ml vs 0.16ng/ml, bacterial vs viral, p = 0.005). Using the ROC curves to discriminate between viral and bacterial CAP generated an area under the curve (AUC) of 0.68 (95% CI 0.53 – 0.83). Based on a threshold procalcitonin level of > 0.5ng/ml, to identify bacterial CAP, gave a sensitivity of 52.2% and a specificity of 82%.

Commenting on their findings, the authors noted that there were no procalcitonin levels which were able to differentiate between bacterial CAP and COVID-19 associated pneumonia. Based on their findings, the authors calculated that the administration of antibiotics to those with procalcitonin levels > 0.5ng/ml would have resulted in the inappropriate treatment of 65.7% of patients with radiological signs of CAP.

They concluded that procalcitonin measurements upon admission in those with suspected CAP cannot accurately differentiate between bacterial or viral CAP.

Citation
Malinverni S et al. Is procalcitonin a reliable marker of bacterial community-acquired pneumonia in adults admitted to the emergency department during SARS-CoV-2 pandemic? Eur J Emerg Med 2021