Additional effect of azithromycin over β-lactam alone for severe community-acquired pneumonia-associated acute respiratory distress syndrome: a retrospective cohort study

Background Community-acquired pneumonia (CAP) is the most common cause of acute respiratory distress syndrome (ARDS). Although previous studies have suggested that macrolide therapy is beneficial for ARDS, its benefit for severe CAP-associated ARDS remains uncertain. Previous studies were limited in that they had a small sample size and included patients with non-pulmonary ARDS and those with pulmonary ARDS. This study aimed to investigate the additional effect of azithromycin when used with β-lactam compared with the effect of β-lactam alone in mechanically ventilated patients with CAP-associated ARDS. Methods We identified mechanically ventilated patients with CAP-associated ARDS between July 2010 and March 2015 using data in the Diagnosis Procedure Combination database, a Japanese nationwide inpatient database. We performed propensity score matching analysis to assess 28-day mortality and in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS who received β-lactam with and without azithromycin within hospital 2 days after admission. The inverse probability of treatment weighting analysis was also conducted. Results Eligible patients (n = 1257) were divided into the azithromycin group (n = 226) and the control group (n = 1031). The one-to-four propensity score matching analysis included 139 azithromycin users and 556 non-users. No significant difference was observed between the groups with respect to 28-day mortality (34.5% vs. 37.6%, p = 0.556) or in-hospital mortality (46.0% vs. 49.1%, p = 0.569). The inverse probability of treatment weighting analysis showed similar results. Conclusions Compared with treatment with β-lactam alone, treatment with azithromycin plus β-lactam had no significant additional effect on 28-day mortality or in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS. To the best of our knowledge, this study is the first to determine the effect of azithromycin in mechanically ventilated patients with CAP-associated ARDS.

Acute respiratory distress syndrome in COVID-19: possible mechanisms and therapeutic management

COVID-19 pandemic is a serious concern in the new era. Acute respiratory distress syndrome (ARDS), and lung failure are the main lung diseases in COVID-19 patients. Even though COVID-19 vaccinations are available now, there is still an urgent need to find potential treatments to ease the effects of COVID-19 on already sick patients. Multiple experimental drugs have been approved by the FDA with unknown efficacy and possible adverse effects. Probably the increasing number of studies worldwide examining the potential COVID-19 related therapies will help to identification of effective ARDS treatment. In this review article, we first provide a summary on immunopathology of ARDS next we will give an overview of management of patients with COVID-19 requiring intensive care unit (ICU), while focusing on the current treatment strategies being evaluated in the clinical trials in COVID-19-induced ARDS patients.

Identified micro-organisms in hospitalized community-acquired pneumonia patients living near goat and poultry farms

Background In the Netherlands, an increased risk of community-acquired pneumonia (CAP) has been reported for adults living near goat and poultry farms. Previous results of respiratory microbiome studies in hospitalized CAP patients near poultry farms suggested a higher relative abundance of Streptococcus pneumoniae. This retrospective study, using routine laboratory data from hospitalized CAP patients, aims to explore possible aetiologic micro-organisms of CAP in relation to livestock exposure. Methods Patient characteristics and PCR and urinary antigen test results were retrieved retrospectively from electronic medical records of CAP patients admitted to the Jeroen Bosch Hospital or Gelre Hospital in the Netherlands during 2016–2017. Distances between the patients’ home address and the nearest poultry and goat farm were calculated. Differences in laboratory test results between CAP patients with and without goat or poultry farms within 2 km of their home address were analyzed using Fisher’s exact test. Results In total, 2230 CAP episodes with diagnostic results were included. In only 25% of the CAP episodes, a micro-organism was detected. A positive urinary antigen test for S. pneumoniae was found more often in patients living within two kilometers of goat (15.2% vs. 11.3%) and poultry farms (14.4% vs. 11.3%), however these differences were not statistically significant (p = 0.1047 and p = 0.1376). Conclusion Our retrospective analysis did not show statistically significant differences in the identified micro-organisms in hospitalized CAP patients related to livestock farming. The study was hampered by limited statistical power and limited laboratory results. Therefore, the potential increased CAP risk around goat and poultry farms will be further explored in a prospective study among CAP patients in primary care.

Candida species in community-acquired pneumonia in patients with chronic aspiration

Background When Candida species is found in a sputum culture, clinicians generally dismiss it as a contaminant. We sought to identify cases of community-acquired pneumonia (CAP) in which Candida might play a contributory etiologic role. Methods In a convenience sample of patients hospitalized for CAP, we screened for “high-quality sputum” by Gram stain (> 20 WBC/epithelial cell) and performed quantitative sputum cultures. Criteria for a potential etiologic role for Candida included the observation of large numbers of yeast forms on Gram stain, intracellular organisms and > 106 CFU/ml Candida in sputum. We gathered clinical information on cases that met these criteria for possible Candida infection. Results Sputum from 6 of 154 consecutive CAP patients had large numbers of extra- and intracellular yeast forms on Gram stain, with > 106 CFU/ml Candida albicans, glabrata, or tropicalis on quantitative culture. In all 6 patients, the clinical diagnoses at admission included chronic aspiration. Greater than 105 CFU/ml of a recognized bacterial pathogen (Streptococcus pneumoniae, Staphylococcus aureus, or Pseudomonas) or > 106 CFU/ml of other ‘normal respiratory flora’ (Lactobacillus species) were present together with Candida spp. in every case. Blood cultures yielded Candida in 2 cases, and 1,3-beta-D glucan was > 500 ng/mL in 3 of 3 cases in which it was assayed. Since all patients were treated with anti-bacterial and anti-fungal drugs, no inference about etiology can be derived from therapeutic response. Conclusions Candida spp. together with a recognized bacterial pathogen or normal respiratory flora may contribute to the cause of CAP in patients who chronically aspirate.

Surfactant protein D: a useful marker for differentiation of drug-induced pneumonia and bacterial pneumonia

Background Drug-induced pneumonia (d-pneumonia) and bacterial pneumonia (b-pneumonia) are often difficult to differentiate; therefore, this study examined the possibility of differentiating them using serum biomarkers. Methods The study included 22 and 16 patients diagnosed with b- and d-pneumonia, respectively, at our institution or affiliated institutions. For d-pneumonia, the causative drug was minocycline hydrochloride in four patients, gefitinib in two patients, nivolumab in two patients, pembrolizumab in two patients, sulfasalazine in two patients, loxoprofen in one patient, Bouiougitou in one patient, edoxaban tosilate hydrate in one patient, and abemaciclib in one patient. White blood cell (WBC), C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, and SP-A levels were measured in each patient and compared between the groups. Results Significant differences were noted in the WBC and SP-D levels between the two groups (P < 0.05, P < 0.001), but not in the CRP, KL-6, or SP-A levels. Conclusion The study results suggest that SP-D is a useful marker for differentiating b-pneumonia and d-pneumonia.

Serotype distribution of invasive, non-invasive and carried Streptococcus pneumoniae in Malaysia: a meta-analysis

Background Pneumococcal pneumonia is the leading cause of under-five mortality globally. The surveillance of pneumococcal serotypes is therefore vital for informing pneumococcal vaccination policy and programmes. Pneumococcal conjugate vaccines (PCVs) have been available as an option in the private healthcare setting and beginning December 2020, PCV10 was incorporated as part of routine national immunisation programme (NIP) in Malaysia. We searched existing literature on pneumococcal serotype distribution across Malaysia to provide an overall view of this distribution before the implementation of PCV10. Methods Online databases (PubMed, Ovid MEDLINE and Scopus), reference lists of articles identified, and grey literature (Malaysian Ministry of Health website, WHO website) were systematically searched for relevant literature on pneumococcal serotype distribution across Malaysia up to 10th November 2020. No lower date limit was set to maximise the number of target reports returned. Results of serotypes were split by age categories, including ≤5 years, > 5 years and unreported for those that did not specify. Results The search returned 18 relevant results, with a total of 2040 isolates. The most common serotypes across all disease types were 19F (n = 313, 15.3% [95%CI: 13.8–17.0]), 23F (n = 166, 8.1% [95%CI: 7.0–9.4]), 14 (n = 166, 8.1% [95%CI: 7.0–9.4]), 6B (n = 163, 8.0% [95%CI: 6.9–9.2]) and 19A (n = 138, 6.8% [95%CI: 5.8–7.9]). Conclusion Four of the most common serotypes across all isolate sources in Malaysia are covered by PCV10, while PCV13 provides greater serotype coverage in comparison to PCV10. There is still a need for surveillance studies, particularly those investigating serotypes in children under 5 years of age, to monitor vaccine effectiveness and pneumococcal population dynamic following implementation of PCV10 into routine immunisation.

Carriage of upper respiratory tract pathogens in rural communities of Sarawak, Malaysian Borneo

Introduction Pneumonia is a leading cause of death in Malaysia. Whilst many studies have reported the aetiology of pneumonia in Western countries, the epidemiology of pneumonia in Malaysia remains poorly understood. As carriage is a prerequisite for disease, we sought to improve our understanding of the carriage and antimicrobial resistance (AMR) of respiratory tract pathogens in Malaysia. The rural communities of Sarawak are an understudied part of the Malaysian population and were the focus of this study, allowing us to gain a better understanding of bacterial epidemiology in this population. Methods A population-based survey of bacterial carriage was undertaken in participants of all ages from rural communities in Sarawak, Malaysia. Nasopharyngeal, nasal, mouth and oropharyngeal swabs were taken. Bacteria were isolated from each swab and identified by culture-based methods and antimicrobial susceptibility testing conducted by disk diffusion or E test. Results 140 participants were recruited from five rural communities. Klebsiella pneumoniae was most commonly isolated from participants (30.0%), followed by Staphylococcus aureus (20.7%), Streptococcus pneumoniae (10.7%), Haemophilus influenzae (9.3%), Moraxella catarrhalis (6.4%), Pseudomonas aeruginosa (6.4%) and Neisseria meningitidis (5.0%). Of the 21 S. pneumoniae isolated, 33.3 and 14.3% were serotypes included in the 13 valent PCV (PCV13) and 10 valent PCV (PCV10) respectively. 33.8% of all species were resistant to at least one antibiotic, however all bacterial species except S. pneumoniae were susceptible to at least one type of antibiotic. Conclusion To our knowledge, this is the first bacterial carriage study undertaken in East Malaysia. We provide valuable and timely data regarding the epidemiology and AMR of respiratory pathogens commonly associated with pneumonia. Further surveillance in Malaysia is necessary to monitor changes in the carriage prevalence of upper respiratory tract pathogens and the emergence of AMR, particularly as PCV is added to the National Immunisation Programme (NIP).

Effect of prophylactic administration of antipyretics on the immune response to pneumococcal conjugate vaccines in children: a systematic review

Background Prophylactic administration of antipyretics at the time of immunization seems to decrease some side effects, however reduced immune responses have been reported in some studies. This systematic review aimed to investigate the effect of prophylactic use of antipyretics on the immune response following administration of pneumococcal conjugate vaccines (PCVs). Methods A systematic review of randomized controlled trials and observational studies concerning the immune response to PCVs after antipyretic administration was performed up to November 2020 in the electronic databases of Pubmed and Scopus. Results Of the 3956 citations retrieved, a total of 5 randomized control trials including 2775 children were included in the review. Included studies were referred to PCV10 (3 studies), PCV7 and PCV13 (one study each). The prophylactic administration of paracetamol decreased the immune response to certain pneumococcal serotypes in all included studies. The effect was more evident following primary vaccination and with immediate administration of paracetamol. Despite the reductions in antibody geometric mean concentrations, a robust memory response was observed following the booster dose. Besides, antibody titers remained above protective levels in 88–100% of participants. The use of ibuprofen, that was evaluated in two studies, did not seem to affect the immunogenicity of PCVs . Conclusion Although the reviewed studies had significant heterogeneity in design, paracetamol administration seems to affect the immune response for certain serotypes. The clinical significance of reduced immunogenicity especially before booster dose needs further investigation.

The role of co-infections and secondary infections in patients with COVID-19

Background It has been recognised for a considerable time-period, that viral respiratory infections predispose patients to bacterial infections, and that these co-infections have a worse outcome than either infection on its own. However, it is still unclear what exact roles co-infections and/or superinfections play in patients with COVID-19 infection. Main body This was an extensive review of the current literature regarding co-infections and superinfections in patients with SARS-CoV-2 infection. The definitions used were those of the Centers for Disease Control and Prevention (US), which defines coinfection as one occurring concurrently with the initial infection, while superinfections are those infections that follow on a previous infection, especially when caused by microorganisms that are resistant, or have become resistant, to the antibiotics used earlier. Some researchers have envisioned three potential scenarios of bacterial/SARS-CoV-2 co-infection; namely, secondary SARS-CoV-2 infection following bacterial infection or colonisation, combined viral/bacterial pneumonia, or secondary bacterial superinfection following SARS-CoV-2. There are a myriad of published articles ranging from letters to the editor to systematic reviews and meta-analyses describing varying ranges of co-infection and/or superinfection in patients with COVID-19. The concomitant infections described included other respiratory viruses, bacteria, including mycobacteria, fungi, as well as other, more unusual, pathogens. However, as will be seen in this review, there is often not a clear distinction made in the literature as to what the authors are referring to, whether true concomitant/co-infections or superinfections. In addition, possible mechanisms of the interactions between viral infections, including SARS-CoV-2, and other infections, particularly bacterial infections are discussed further. Lastly, the impact of these co-infections and superinfections in the severity of COVID-19 infections and their outcome is also described. Conclusion The current review describes varying rates of co-infections and/or superinfections in patients with COVID-19 infections, although often a clear distinction between the two is not clear in the literature. When they occur, these infections appear to be associated with both severity of COVID-19 as well as poorer outcomes.