Time dependent enhanced resistance against antibiotics & metal salts by planktonic & biofilm form of Acinetobacter haemolyticus MMC 8 clinical isolate

Background & objectives: Available literature shows paucity of reports describing antibiotic and metal resistance profile of biofilm forming clinical isolates of Acinetobacter haemolyticus. The present study was undertaken to evaluate the antibiotic and metal resistance profile of Indian clinical isolate of A. haemolyticus MMC 8 isolated from human pus sample in planktonic and biofilm form. Methods: Antibiotic susceptibility and minimum inhibitory concentration were determined employing broth and agar dilution techniques. Biofilm formation was evaluated quantitatively by microtiter plate method and variation in complex architecture was determined by scanning electron microscopy. Minimum biofilm inhibiting concentration was checked by Calgary biofilm device. Results: Planktonic A. haemolyticus MMC 8 was sensitive to 14 antibiotics, AgNO 3 and HgC1 2 resistant to streptomycin and intermediately resistant to netilmycin and kanamycin. MMC 8 exhibited temporal variation in amount and structure of biofilm. There was 32 - 4000 and 4 - 256 fold increase in antibiotic and metal salt concentration, respectively to inhibit biofilm over a period of 72 h as against susceptible planktonic counterparts. Total viable count in the range of 10 5 -10 6 cfu / ml was observed on plating minimum biofilm inhibiting concentration on Muller-Hinton Agar plate without antimicrobial agents. Biofilm forming cells were several folds more resistant to antibiotics and metal salts in comparison to planktonic cells. Presence of unaffected residual cell population indicated presence of persister cells. Interpretation & conclusions: The results indicate that biofilm formation causes enhanced resistance against antibiotics and metal salts in otherwise susceptible planktonic A. haemolyticus MMC 8

Outcomes of multivariable analyses of predictors associated with abnormal DLco.

Outcomes of multivariable analyses of predictors associated with abnormal DLco.</p

Minimal required data set.

ObjectivesAn isolated reduction in the diffusing capacity for carbon monoxide (DLco; iso↓DLco) is one of the most common pulmonary function test (PFT) abnormalities in people living with HIV (PWH), but its clinical implications are incompletely understood. In this study, we explored whether iso↓DLco in PWH is associated with a greater respiratory symptom burden.Study designCross-sectional analysisMethodsWe used ATS/ERS compliant PFTs from PWH with normal spirometry (post-bronchodilator FEV1/FVC ≥0.7; FEV1, FVC ≥80% predicted) from the I AM OLD cohort in San Francisco, CA and Seattle, WA, grouped by DLco categorized as normal (DLco ≥lower limit of normal, LLN), mild iso↓DLco (LLN >DLco >60% predicted), and moderate-severe iso↓DLco (DLco ≤60% predicted). We performed multivariable analyses to test for associations between DLco and validated symptom-severity and quality of life questionnaires, including the modified Medical Research Council dyspnea scale (mMRC), the COPD Assessment Test (CAT), and St. George’s Respiratory Questionnaire (SGRQ), as well as between DLco and individual CAT symptoms.ResultsMild iso↓DLco was associated only with a significantly higher SGRQ score. Moderate-severe iso↓DLco was associated with significantly higher odds of mMRC ≥2 and significantly higher CAT and SGRQ scores. PWH with moderate-severe iso↓DLco had increased odds of breathlessness, decreased activity, lower confidence leaving home, and less energy.ConclusionsIso↓DLco is associated with worse respiratory symptom scores, and this association becomes stronger with worsening DLco, suggesting that impaired gas exchange alone has a significant negative impact on the quality of life in PWH. Additional studies are ongoing to understand the etiology of this finding and design appropriate interventions.</div

Fig 3 -

a. Distribution of CAT scores by DLco category. Mantel-Haenszel test was used to test for a linear trend between CAT scores and DLco category [Ptrend Ptrend b. Distribution of SGRQ scores by DLco category. Kruskal-Wallis test was used to test for a linear trend between SGRQ scores and DLCO category [Ptrend Ptrend < 0.001 (**)].</p

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

International audienceLife-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population