Clinical and Microbiological Characteristics of Mycobacterium kansasii Pulmonary Infections in China

M. kansasii type I is the main genotype spreading worldwide. The molecular history of the global spread of type I isolates remains largely unclear. We conducted a detailed analysis of genomic evolution of global M. kansasii isolates. Our results suggest that M. kansasii isolates exhibit greater genetic diversity globally.

10-DEBC Hydrochloride as a Promising New Agent against Infection of Mycobacterium abscessus

Mycobacterium abscessus (M. abscessus) causes chronic pulmonary infections. Its resistance to current antimicrobial drugs makes it the most difficult non-tuberculous mycobacteria (NTM) to treat with a treatment success rate of 45.6%. Therefore, there is a need for new therapeutic agents against M. abscessus. We identified 10-DEBC hydrochloride (10-DEBC), a selective AKT inhibitor that exhibits inhibitory activity against M. abscessus. To evaluate the potential of 10-DEBC as a treatment for lung disease caused by M. abscessus, we measured its effectiveness in vitro. We established the intracellular activity of 10-DEBC against M. abscessus in human macrophages and human embryonic cell-derived macrophages (iMACs). 10-DEBC significantly inhibited the growth of wild-type M. abscessus and clinical isolates and clarithromycin (CLR)-resistant M. abscessus strains. 10-DEBC’s drug efficacy did not have cytotoxicity in the infected macrophages. In addition, 10-DEBC operates under anaerobic conditions without replication as well as in the presence of biofilms. The alternative caseum binding assay is a unique tool for evaluating drug efficacy against slow and nonreplicating bacilli in their native caseum media. In the surrogate caseum, the mean undiluted fraction unbound (fu) for 10-DEBC is 5.696. The results of an in vitro study on the activity of M. abscessus suggest that 10-DEBC is a potential new drug for treating M. abscessus infections.

Pseudomonas aeruginosa associated pulmonary infections and in vitro amplification virulent rhamnolipid (rhlR) gene

Background Pseudomonas aeruginosa is a common opportunistic pathogenic bacterium with the ability to develop a strong communication pathway by quorum sensing system and different virulent factors. Among the various important secretions of P. aeruginosa rhamnolipid is important biological detergent, believed to be involved in the development of the biofilm and intercellular communication. It readily dissolves the lung surfactants that are then easily catalyzed by the phospholipases and in this way is involved in the acute pulmonary infection. Objective research work was designed to investigate virulence and gene associated with virulence in P. aeruginosa responsible for pulmonary infections. Methods In current study polymerase chain reaction (PCR) was used for the detection of the rhlR (rhamnolipid encoding) gene of isolated strains. A number of assays were performed that ensured its virulent behavior. Disc diffusion method was used to check its antibiotic resistance. Isolated strains were resistant to a number of antibiotics applied. Result It was found that males are more prone to respiratory infections as compared to females. Male members with age of 44-58 and 59-73 are at a higher risk, while females with age of 44-58 are also at a risk of pulmonary infections. Antibiotic resistance was observed by measuring zone of inhibition in strains GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 and GCU-SG-M6. GCU-SG-M2 was resistant to fluconazole (FLU), clarithromycin (CLR), cefixime (CFM) and Penicillin (P10). No zone of inhibition was observed. But it showed unusual diffused zone around the Ak and MEM antibiotic discs. rhl R gene and 16s rRNA gene were characterized and analyzed. Conclusion Findings from current study would help in raising awareness about antibiotic resistance of P. aeruginosa, and also the sequence of rhl R gene can be used as the diagnostic marker sequence to identify the virulent rhl R gene sequence from the samples when isolated from sputum of Pneumonia patients.

Leptin in the Respiratory Tract: Is There a Role in SARS-CoV-2 Infection?

Leptin is a pleiotropic adipocytokine involved in several physiologic functions, with a known role in innate and adaptive immunity as well as in tissue homeostasis. Long- and short-isoforms of leptin receptors are widely expressed in many peripheral tissues and organs, such as the respiratory tract. Similar to leptin, microbiota affects the immune system and may interfere with lung health through the bidirectional crosstalk called the “gut-lung axis.” Obesity leads to impaired protective immunity and altered susceptibility to pulmonary infections, as those by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it is known that leptin and microbiota link metabolism and lung health, their role within the SARS-CoV2 coronavirus disease 2019 (COVID-19) deserves further investigations. This review aimed to summarize the available evidence about: (i) the role of leptin in immune modulation; (ii) the role of gut microbiota within the gut-lung axis in modulating leptin sensitivity; and (iii) the role of leptin in the pathophysiology of COVID-19.

Prospects of Inhaled Phage Therapy for Combatting Pulmonary Infections

With respiratory infections accounting for significant morbidity and mortality, the issue of antibiotic resistance has added to the gravity of the situation. Treatment of pulmonary infections (bacterial pneumonia, cystic fibrosis-associated bacterial infections, tuberculosis) is more challenging with the involvement of multi-drug resistant bacterial strains, which act as etiological agents. Furthermore, with the dearth of new antibiotics available and old antibiotics losing efficacy, it is prudent to switch to non-antibiotic approaches to fight this battle. Phage therapy represents one such approach that has proven effective against a range of bacterial pathogens including drug resistant strains. Inhaled phage therapy encompasses the use of stable phage preparations given via aerosol delivery. This therapy can be used as an adjunct treatment option in both prophylactic and therapeutic modes. In the present review, we first highlight the role and action of phages against pulmonary pathogens, followed by delineating the different methods of delivery of inhaled phage therapy with evidence of success. The review aims to focus on recent advances and developments in improving the final success and outcome of pulmonary phage therapy. It details the use of electrospray for targeted delivery, advances in nebulization techniques, individualized controlled inhalation with software control, and liposome-encapsulated nebulized phages to take pulmonary phage delivery to the next level. The review expands knowledge on the pulmonary delivery of phages and the advances that have been made for improved outcomes in the treatment of respiratory infections.

Early Multicenter Experience With Imipenem-Cilastatin-Relebactam for Multidrug-Resistant Gram-Negative Infections

A multicenter case series of 21 patients were treated with imipenem-cilastatin-relebactam. There were mixed infection sources, with pulmonary infections (11/21,52%) composing the majority. The primary pathogen was Pseudomonas aeruginosa (16/21, 76%), and 15/16 (94%) isolates were multidrug-resistant. Thirty-day survival occurred in 14/21 (67%) patients. Two patients experienced adverse effects.

P-OGC28 Totally minimally invasive Oesophagectomies(Robotic & laparoscopic) are associated with an improved immediate post operative outcomes in comparison with open oesophagectomies;an upshot of a systematic review and metanalysis

Background Radical oesophagectomy is the recognized standard curative surgery for operable oesophageal cancers. Postoperative morbidity and mortality are considerable following open oesophagectomy. Minimally invasive techniques- (thoraco-laparoscopy and robotic surgery) has evolved as an alternative for open techniques. Oncological outcomes, tumor clearance, lymph node yield, anastomotic leak, in-hospital and 30-day mortality are comparable between open and MIS techniques in various studies. Short term benefits like pulmonary complications, post-op quality of life, operative time, blood loss, pain control have not been studied widely. This meta-analysis aims at evaluation of randomized trials that compare short term outcomes of totally minimally invasive versus open oesophagectomies Methods Three articles were selected after a systematic search of the literature. Methodological quality was assessed by Jadad scoring. Cochrane Risk of Bias (RoB) assessment tool was applied to determine the impact of bias. Pulmonary infections, Health-related quality of life EORTC C30 score, blood loss, operating time, 10-day pain score was recorded. CASP tool questionnaire was applied to individual studies by two authors separately. A random-effects model used to determine the overall effect. Weighted mean difference (WMD) or standardized mean difference (SMD) with 95%CI is calculated for continuous variable and Odds ratio for dichotomous variables. Heterogeneity between studies was measured using the Chi-square test and I2 test Results A total of 338 patients have been included. All baseline characteristics are matched to eliminate bias. Review results showed a statistically significant lower rate of pulmonary infections in MIS oesophagectomy with odds ratio 3.63 (2.09, 6.31; p-value<0.00001). Postoperative QoL EORTC C30 was better in MIS group with SMD of 0.80 (0.57, 1.02; p-value<0.00001). Operating time was significantly longer in the MIS technique, SMD of 1.50 (1.20, 1.80; p-value <0.00001). The blood loss was significantly lower in the MIS group with SMD -1.74; p-value <0.00001. MIS had significantly lower pain scores compared to open surgeries with SMD of -0.39 (-0.66,-0.13; p-value 0.004) Conclusions The meta-analysis showed a significant difference in postoperative pulmonary infections and health-related quality of life, favoring totally minimally invasive surgeries for oesophagectomies done for resectable oesophageal cancers. Other outcomes like pain control, blood loss was also better in minimally invasive groups. These benefits could outweigh the longer operating time in minimally invasive surgeries. With time, after the steep learning curve is achieved, totally minimally invasive oesophagectomies will possibly be a better alternative to open surgeries in terms of short term postoperative outcomes

P-OGC14 Global Level of Harm Upper Gastrointestinal (GLEOHUG) – a multinational gastric cancer cross- sectional appraisal

Background Gastric cancer (GC) is the 5th most common malignancy and remains one of the major causes of worldwide cancer-related deaths. COVID-19 pandemic has had a significant impact on the provision of cancer care. This study aims to overview the global standpoint of gastric cancer patients (GCP) during the first year of the pandemic. Methods The Upper Gastrointestinal Surgeons (TUGS), within its Global Level of Harm Project, designed an online cross-sectional survey to assess how gastric cancer patient’s management changed during the first year of the pandemic. The questionnaire included 33 questions about expertise, kind of health system, hospital organization and screening policies, personal protective equipment (PPE), change in patient’s characteristics, preoperative, operative and postoperative management of GCP. Results There were 209 participants from 178 centres & 50 countries). Results showed: most hospitals (88,18%) had restricted areas for COVID-19 patients; 53.58% of surgeons were redeployed; most frequent COVID-19 screening method was PCR (78,82%) & chest CT-scan (25,62%), and 55.98% lack full PPE. Preoperative management: 43.16% noted reduction in multidisciplinary teams (MDT) meetings; 28,42% increase in cT2 or higher GCP; 34,74% increase in metastatic (M1) GCP; 26,84% increase in patients receiving definitive palliative treatment; 23,68% note increase in frail patients; 50% increase in waiting list time; and 41,58% faced problems in the provision of oncological treatment. Operative management: 54,50% decrease in elective gastrectomies; 29,10% increase in urgent/semi-urgent gastrectomies; 37,04% decrease in the number of minimally-invasive gastrectomies (MIG); & 18,52% increase in the number of palliative surgeries. Postoperative management: 16,48% increase in the overall complication rate (OCR); 12,64% increase in the number of Clavien-Dindo 3 or higher complications; 8,13% increase in the leak rate; increase in pulmonary infections (26,79%) and bowel obstruction (2,39%); 44,51% note postoperative COVID-19; 15,38% increase in 30-days mortality; 23,08% mortality due to COVID-19 infection; 17,58% increase in the need for adjuvant treatment. Most patients were postoperatively assessed either through a face-to-face consultation or a hybrid approach. Conclusions COVID-19 pandemic has affected gastric cancer management by decreased frequency of MDT’s, higher clinical-stage migration and fuelled frailty. The pandemic increased waiting list time, the number of urgent and palliative surgeries, OCR, Clavie-Dindo 3 or higher complications, leak rate, and pulmonary infections. There was a noticeable high rate of postoperative COVID-19 infection and associated mortality. Further multicentric studies are warranted to affirm these findings.

High Rates of Bacterial Pulmonary Co-Infections and Superinfections Identified by Multiplex PCR among Critically Ill COVID-19 Patients

Background: The role of bacterial co-infection and superinfection among critically ill COVID-19 patients remains unclear. The aim of this study was to assess the rates and characteristics of pulmonary infections, and associated outcomes of ventilated patients in our facility. Methods: This was a retrospective study of ventilated COVID-19 patients between March 2020 and March 2021 that underwent BioFire®, FilmArray® Pneumonia Panel, testing. Community-acquired pneumonia (CAP) was defined when identified during the first 72 h of hospitalization, and ventilator-associated pneumonia (VAP) when later. Results: 148 FilmArray tests were obtained from 93 patients. With FilmArray, 17% of patients had CAP (16/93) and 68% had VAP (64/93). Patients with VAP were older than those with CAP or those with no infection (68.5 vs. 57–59 years), had longer length of stay and higher mortality (51% vs. 10%). The most commonly identified FilmArray target organisms were H. influenzae, S. pneumoniae, M. catarrhalis and E. cloacae for CAP and P. aeruginosa and S. aureus for VAP. FilmArray tests had high negative predictive values (99.6%) and lower positive predictive values (~60%). Conclusions: We found high rates of both CAP and VAP among the critically ill, caused by the typical and expected organisms for both conditions. VAP diagnosis was associated with poor patient outcomes.