Exploring Synergistic Combinations in Extended and Pan-Drug Resistant (XDR and PDR) Whole Genome Sequenced Acinetobacter baumannii.

Background: The diminishing antimicrobial options for the treatment of XDR and PDR Acinetobacter baumannii is an increasing concern. In this study, we assessed the in vitro synergy of the fosfomycin (FOS) with meropenem (MEM), amikacin (AK), tigecycline (TGC), and colistin (CL) in whole genome sequenced isolates. Methods: Non-replicate whole genome sequenced (illumina next-generation sequencing platform, Clevergene, India), A. baumanii (7 XDR, 1PDR) were subjected to in vitro synergy testing by checkerboard (CB) and time kill assay (TKA) after MIC determination, with glucose-6-phosphate being incorporated in all runs. FOS was used as a cornerstone drug in four combinations and colistin in one. ResFinder, MLST, PlasmidFinder, and CSIPhylogeny tools were used. Results: Mortality occurred in three patients. Diverse MLST were observed, ST-1962 (3 isolates) and one each of ST2062, ST2063, ST1816, ST1806, ST234. FOS MICs ranged from 32 to 128 mg/L, MEM MIC: 16-64 mg/L, TGC MIC: ≤2-≤4 mg/L and AK MIC: >512 mg/L. CL: MIC range, 0.25-≤2 mg/L, PDR MIC > 16 mg/L. Synergy results by CB: FOS-MEM: synergy in ⅞ (90%) isolates. Synergy lowered MEM MICs to susceptibility breakpoints in 6/8 cases. CL-MEM: Excellent synergy (3/3) isolates. FOS-AK: Indifference in ⅞, antagonism ⅛ (AK-susceptible isolate). FOS-TGC: Partial synergy (PS) in 8/8 (TGC MIC dropped to ≤0.25 mg/L in 3/8). In the PDR isolate, synergy was seen in FOS-MEM, CL-MEM, PS in FOS-CL, FOS-TGC, indifference in FOS-AK. TKA: Excellent synergy was observed with FOS-MEM from 4 h, while FOS-AK and FOS-TGC demonstrated synergy at 24 h. Synergy was achieved despite presence of widespread resistance markers against aminoglycosides (AacAad, AadA, AadB, Aph3″Ia, ArmA, Arr, StrA, StrB), beta-lactams (ADC, BlaA1, BlaA2, Zn-dependent_hydrolase, OXA-23, OXA-51, PER-1,TEM-1D, CARB-5, Mbl), sulphonamides (SulII, SulI), phenicols (CatBx, CmlA), macrolides (MphE, MsrE) and tetracycline (TetB) were widespread. Carbapenemase, CARB-5 was present in one isolate. Beta-lactamase genes OXA-23, OXA-51, BlaA2, Zn-dependent_hydrolase, ADC, Mbl and macrolide resistance genes MphE, MsrE were present in all 8 isolates. Conclusions: FOS-MEM and CL-MEM are promising combinations against A. baumannii. Synergy of FOS-MEM in intrinsically resistant A. baumannii shows that this antibiotic combination might be useful in treating such XDR and PDR pathogens.

Caecal Ameboma, colorectal malignancy mimicker in young male with ANCA-associated vasculitis.

Ameboma refers to the rare development of an inflammatory, ulcerated, exophytic mass in the gastrointestinal tract that can resemble carcinoma. Typically it presents as a right lower quadrant abdominal mass, Patients may also present with diarrhea or constipation and associated systemic symptoms, including weight loss and fever. In this article we present a young man with a background of ANCA associated vasculitis, who presented with fresh lower gastrointestinal bleeding during hospital admission for severe covid-19 pneumonia which turned out to be caecal aemboma. This case is highlighted for its rarity, the diagnostic challenge, and for the major role of colonoscopy as a diagnostic tool for this pathology.

Short and long-term immune changes in different severity groups of COVID-19 disease.

BACKGROUND: There are limited data on short- versus long-term changes in adaptive immune response across different COVID-19 disease severity groups. METHODS: A multicenter prospective study of 140 adult patients with COVID-19 (a total of 325 samples) were analyzed for inflammatory markers and lymphocyte subsets at presentation, week 2, and week 24. RESULTS: Inflammatory markers at presentation were higher in the critical/severe than in moderate and mild groups. A predominance of memory B cell response in the mild and moderate group was noted by week 2. In contrast, the immune system in the severe/critical group was dysfunctional, with expansion of exhausted CD8+ T cells and atypical memory B cells. By 24 weeks, there was a possible trend of normalization. CONCLUSION: There was substantial difference in the degree of inflammation and distribution of different B and T cell subsets in the different disease severity groups. Despite the initial dysfunctional immune response in the severe/critical group, a comparable memory B and CD8+ T cell responses to the mild group was achieved at 24 weeks.

Validation of the existing modified screening criteria for detection of all cases of Retinopathy of Prematurity in preterm babies - 11 year study from a governorate referral hospital in Oman.

PURPOSE: To study appropriateness of our modified screening criteria for detection of all cases of Retinopathy of Prematurity (ROP) among preterm babies. METHOD: Retrospective observational cohort study among preterm neonates who underwent ROP screening as per set protocol for 11 years at Nizwa Hospital, Al Dhakilya Governorate, Oman. We screened all babies with gestational age ⩽32 weeks or BW â©½ 1500 g. Preterm babies >32 weeks of GA or BW > 1500 g with unstable clinical course believed to be at high risk by the attending neonatologist also were screened. RESULTS: During the study period 528 babies were screened for ROP of which 76 babies were excluded due to death, associated congenital ocular malformation and loss for follow-up either due to transfer to other institution or defaulting. Thus 452 babies were included in the final analysis. Incidence of ROP was 46.4% of which 27.9% had mild ROP, 11.3% had severe ROP which regressed and 7.3% had severe ROP who were treated. The incidence of ROP among infants with GA < 26 wks, 26-28 wks, 29-30 wks, 31-32 wks and above 32 weeks was 100.0%, 80.0%, 59.3%, 34.4% and 19.4% respectively. 56 babies of this cohort belonged to Extended (modified) criteria group. Among these 12 babies had ROP out of which 9 had mild ROP and 3 had severe ROP. Among cases with severe ROP, two cases regressed spontaneously and one case needed treatment. Multivariate analysis using stepwise regression model showed statistically significant association of GA and BW to development of ROP. We would have missed few babies with ROP if we had followed other criteria. CONCLUSION: Our modified screening criteria seem to be appropriate as no infant with severe ROP was missed during the study period. Incidence of severe ROP among babies in the extended criteria group (5.4%) is low but significant compared to lower gestational age. We plan to formulate a scoring system following all risk factor analysis to enable us to optimize the number of infants screened. Detection of all babies with ROP is important as they need long-term follow-up for the timely detection and management of associated ocular comorbidities.