Relationship between biofilm-forming microorganisms (BFM: Staphylococcus aureus and Pseudomonas aeruginosa) and DEFB1 gene variants on ß-defensin levels in periprosthetic joint infection (PJI).

BACKGROUND: The purpose of this study was to investigate the relationship between biofilm-forming microorganisms (BFM) and DEFB1 gene variants on ß-defensin levels in patients with periprosthetic joint infection (PJI) of Mexican origin. METHODS AND RESULTS: One hundred and five clinical aspirates were obtained from patients with suspected PJI. After microbiologic culture, samples were classified as non-septic and septic; of the latter, only those positive for Staphylococcus aureus and Pseudomonas aeruginosa were selected. ß-Defensin levels were quantified by ELISA, DNA was extracted from total leukocytes of the samples, and - 20G > A (rs11362) and - 44 C > G (rs1800972) variants were genotyped using TaqMan probes. Forty-one clinical aspirates were non-septic, 18 were positive for S. aureus and 18 were positive for P. aeruginosa. It was observed that ß-defensin levels were higher in the P. aeruginosa group compared to S. aureus group (2339.0 pg/mL IQR = 1809.2 vs. 1821.3 pg/mL IQR = 1536.4) and non-septic group (2339.0 pg/mL IQR = 1809.2 vs. 1099.7 pg/mL IQR = 1744.5, P < 0.001). The CG genotype of the rs1800972 variant was associated with higher ß-defensin levels compared to the CC genotype for both P. aeruginosa and S. aureus (1905.8 vs. 421.7 pg/mL, P = 0.004; and 1878.2 vs. 256.4 pg/mL, P = 0.006, respectively). CONCLUSIONS: Our results show that ß-defensin levels are significantly elevated in patients with BFM-associated PJI compared to those without infection. Furthermore, carriers of the CG genotype of the rs1800972 variant have an increased risk of PJI. Further research is needed to replicate these findings in a larger population.

Association of TLR4 gene polymorphisms with sepsis after a burn injury: findings of the functional role of rs2737190 SNP.

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated response to an infection that is common among patients with moderate to severe burn injury. Previously, genomic variants in Toll-like receptor 4 (TLR4), a key innate immunity receptor, have been associated with sepsis and infection susceptibility. In this study, the association of six TLR4 SNPs with sepsis after burn injury was tested in the Mexican mestizo population. We found that the rs2737190 polymorphism is associated with sepsis after burn trauma. Interestingly, the G allele and GG genotype were associated with a lower risk of developing sepsis. Since the rs2737190 SNP is in the promoter region of the TLR4 gene, we analyzed the possibility that this polymorphism regulates the TLR4 pathway. We cultured peripheral blood mononuclear cells from different genotype carriers and found, after stimulation with LPS, that carriers of the GG genotype showed a higher expression of TLR4, IL6, and TNFα than AA genotype carriers. The results suggest that the GG genotype produces an increase in the TLR4 expression, and therefore an improvement in the immune response. We conclude that the rs2737190 polymorphism may become a useful marker for genetic studies of sepsis in patients after a burn injury.

Surveillance of antimicrobial resistance in Serratia marcescens in Mexico.

Antimicrobial resistance is a global public health threat. Therefore, surveillance studies are important tools to help direct antimicrobial use. The aim of this study was to investigate antimicrobial resistance in Serratia marcescens isolates collected in 2016-2017 at eight medical centers from two regions of Mexico. Selected S. marcescens isolates were further tested by polymerase chain reaction to detect the presence of genes encoding the ß-lactamases, SHV, TEM or CTX. Antimicrobial resistance continues to be high in Mexico, particularly to ciprofloxacin and aminoglycosides. Also, a widespread prevalence of blaTEM was detected in S. marcescens isolates.

Randomized Controlled Trial to Reduce Bacterial Colonization of Surgical Drains with the Use of Chlorhexidine-Coated Dressings After Breast Cancer Surgery.

BACKGROUND: Breast surgery is considered a clean surgery. However, surgical-site infection (SSI) rates are currently higher than predicted. Postoperative drains remain in situ for several days, with inevitable bacterial colonization and increased SSI risk. METHODS: This randomized controlled trial from October 2016 to January 2018 analyzed patients undergoing breast cancer surgery. The patients were randomized to either the standard drain care group or the antiseptic dressing group (3M® Tegaderm® CHG). Drain samples taken on postoperative days (PODs) 7 and 14 were cultured as standardized in the laboratory. Colonization rates and SSI were compared between the two groups. RESULTS: The study enrolled 104 patients with 167 surgical drains. The patients' clinical characteristics were similar in the two groups, with no statistically significant differences. Bulb fluid cultures at postoperative week (POW) 1 were positive for 42.9% of the control group and 28.9% of the antiseptic group (p = 0.06). Cultures from the POW 2 assessment were positive for 79.7% of the control group versus 54.9% of the antiseptic group (p = 0.001). Cultures from drain tubes were positive for 79.8% of the control group and 50.7% of the antiseptic group (p = < 0.001). In 11 patients, an SSI developed, 3 (5.8%) from the intervention and 8 (15.4%) from the control procedure (p = 0.11). CONCLUSION: The study findings demonstrated that the use of antiseptics at the drain exit site significantly reduced bacterial colonization of the closed drainage system in breast cancer surgery. Semi-permeable occlusive chlorhexidine-impregnated dressings provide an opportunity to test simple, safe, and low-cost interventions that may reduce drain bacterial colonization and SSI after breast surgery.

Leuconostoc mesenteroides periprosthetic knee infection, an unusual fastidious Gram-positive bacteria: a case report.

BACKGROUND: Periprosthetic joint infections are mainly caused by Gram-positive cocci. Leuconostoc mesenteroides is a rare microorganism mainly causing bloodstream infections. At times, it might be confused with another type of cocci and give rise to misdiagnosed infections. Molecular diagnosis and biofilm production comprise important techniques to guide antibiotic treatment. CASE PRESENTATION: A 68-year-old Hispanic female with a previous history of bilateral knee arthroplasty presented with acute right-knee inflammation and gait impairment. Blood tests showed inflammatory response and knee x-ray revealed no prosthesis loosening. Irrigation and debridement was performed. Gram-positive cocci were obtained from cultures, and then biochemical and molecular identification revealed L. mesenteroides. Susceptibility and biofilm production were performed. The patient was treated with IntraVenous (IV) Ceftriaxone for ten days and was then switched to Amoxicillin-Clavulanate for 3 months with clinical and laboratory success. CONCLUSIONS: Microbiology diagnosis of fastidious microorganisms is mandatory to treat periprosthetic joint infections adequately. L. mesenteroides may infect non-immunocompromised persons; however, treatment guidelines are lacking.

Higher In vitro Proliferation Rate of Rhizopus oryzae in Blood of Diabetic Individuals in Chronic Glycaemic Control Compared with Non-diabetic Individuals.

Metabolic control improves outcomes associated with mucormycosis. The aim of this study was to compare the in vitro proliferation of Rhizopus oryzae in blood of individuals with and without diabetes at different glycaemic levels. Ninety-five individuals were included. Blood samples from each participant were incubated with sporangiospores of R. oryzae. The germination, filamentation and growth of R. oryzae were compared at different time points. Four groups were defined, one without (group A, n = 30) and three with diabetes: group B (HbA1c ≤7%, N = 24), group C (HbA1c 7.1-9%, N = 20) and group D (HbA1c > 9%, N = 21). The percentage of germinated sporangiospores was higher in the group A after 6 h (group A 56% ± 3, group B 35% ± 4, group C 48% ± 4, group D 46% ± 1.4, p = 0.01), 12 h (group A 54% ± 1.4, group B 19% ± 4, group C 16% ± 1, group D 9.5% ± 5, p < 0.001) and 24 h (group A 29% ± 1, group B 12% ± 4, group C 13.5% ± 3.5, group D 12% ± 1, p < 0.01). The filamentation was higher in groups with diabetes. Group B showed higher filamentation grade than group A at 6 h (0.4 ± 0.04 vs 1 ± 0.09, p < 0.001) and 24 h (1.6 ± 0.05 vs 2.1 ± 0.1, p = 0.05). In conclusion, R. oryzae proliferation was higher among diabetic individuals, including good glycaemic control, than among non-diabetic individuals.

In vitro activity of ceftazidime/avibactam, cefiderocol, meropenem/vaborbactam and imipenem/relebactam against clinical strains of the Stenotrophomonas maltophilia complex.

BACKGROUND: Infections caused by Stenotrophomonas maltophilia and related species are increasing worldwide. Unfortunately, treatment options are limited, whereas the antimicrobial resistance is increasing. METHODS: We included clinical isolates identified as S. maltophilia by VITEK 2 Compact. Ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, quinolones, and tetracycline family members were evaluated by broth microdilution method and compared with first-line treatment drugs. Minimum inhibitory concentrations (MICs) were reported for all antibiotics. We sequenced the Whole Genome of cefiderocol resistant strains (CRSs) and annotated their genes associated with cefiderocol resistance (GACR). Presumptive phylogenetic identification employing the 16S marker was performed. RESULTS: One hundred and one clinical strains were evaluated, sulfamethoxazole and trimethoprim, levofloxacin and minocycline showed susceptibilities of 99.01%, 95.04% and 100% respectively. Ceftazidime was the antibiotic with the highest percentage of resistance in all samples (77.22%). Five strains were resistant to cefiderocol exhibiting MIC values ≥ 2 µg/mL (4.95%). The ß-lactamase inhibitors meropenem/vaborbactam and imipenem/relebactam, failed to inhibit S. maltophilia, preserving both MIC50 and MIC90 ≥64 µg/mL. Ceftazidime/avibactam restored the activity of ceftazidime decreasing the MIC range. Tigecycline had the lowest MIC range, MIC50 and MIC90. Phylogeny based on 16S rRNA allowed to identify to cefiderocol resistant strains as putative species clustered into Stenotrophomonas maltophilia complex (Smc). In these strains, we detected GARCs such as Mutiple Drug Resistance (MDR) efflux pumps, L1-type ß-lactamases, iron transporters and type-1 fimbriae. CONCLUSION: Antimicrobial resistance to first-line treatment is low. The in vitro activity of new ß-lactamase inhibitors against S. maltophilia is poor, but avibactam may be a potential option. Cefiderocol could be considered as a potential new option for multidrug resistant infections. Tetracyclines had the best in vitro activity of all antibiotics evaluated.

Pseudomonas aeruginosa Isolates from Water Samples of the Gulf of Mexico Show Similar Virulence Properties but Different Antibiotic Susceptibility Profiles than Clinical Isolates.

Pseudomonas aeruginosa is an opportunistic pathogen found in a wide variety of environments, including soil, water, and habitats associated with animals, humans, and plants. From a One Health perspective, which recognizes the interconnectedness of human, animal, and environmental health, it is important to study the virulence characteristics and antibiotic susceptibility of environmental bacteria. In this study, we compared the virulence properties and the antibiotic resistance profiles of seven isolates collected from the Gulf of Mexico with those of seven clinical strains of P. aeruginosa. Our results indicate that the marine and clinical isolates tested exhibit similar virulence properties; they expressed different virulence factors and were able to kill Galleria mellonella larvae, an animal model commonly used to analyze the pathogenicity of many bacteria, including P. aeruginosa. In contrast, the clinical strains showed higher antibiotic resistance than the marine isolates. Consistently, the clinical strains exhibited a higher prevalence of class 1 integron, an indicator of anthropogenic impact, compared with the marine isolates. Thus, our results indicate that the P. aeruginosa marine strains analyzed in this study, isolated from the Gulf of Mexico, have similar virulence properties, but lower antibiotic resistance, than those from hospitals.

Carbapenem-Resistant Gram-Negative Bacilli Characterization in a Tertiary Care Center from El Bajio, Mexico.

Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a major public health concern. We aimed to evaluate the prevalence of CR-GNB and the frequency of carbapenemase-encoding genes in a tertiary referral center from El Bajio, Mexico. A cross-sectional study was conducted between January and October 2022; Gram-negative bacilli (GNB) were screened for in vitro resistance to at least one carbapenem. CR-GNB were further analyzed for carbapenemase-production through phenotypical methods and by real-time PCR for the following genes: blaKPC, blaGES, blaNDM, blaVIM, blaIMP, and blaOXA-48. In total, 37 out of 508 GNB were carbapenem-resistant (7.3%, 95% CI 5.2-9.9). Non-fermenters had higher rates of carbapenem resistance than Enterobacterales (32.5% vs. 2.6%; OR 18.3, 95% CI 8.5-39, p < 0.0001), and Enterobacter cloacae showed higher carbapenem resistance than other Enterobacterales (27% vs. 1.4%; OR 25.9, 95% CI 6.9-95, p < 0.0001). Only 15 (40.5%) CR-GNB had a carbapenemase-encoding gene; Enterobacterales were more likely to have a carbapenemase-encoding gene than non-fermenters (63.6% vs. 30.8%, p = 0.08); blaNDM-1 and blaNDM-5 were the main genes found in Enterobacterales; and blaIMP-75 was the most common for Pseudomonas aeruginosa. The mcr-2 gene was harbored in one polymyxin-resistant E. cloacae. In our setting, NDM was the most common carbapenemase; however, less than half of the CR-GNB showed a carbapenemase-encoding gene.

Comparison of Lateral Flow Immunochromatography and Phenotypic Assays to PCR for the Detection of Carbapenemase-Producing Gram-Negative Bacteria, a Multicenter Experience in Mexico.

The identification of carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa is important for treating and controlling hospital infections. The recommended methods for their identification require a long waiting time, technical training, and expertise. Lateral flow immunoassays such as NG-Test CARBA 5® overcome these needs. We analyzed 84 clinical isolates of carbapenem-resistant Enterobacterales and P. aeruginosa from four different hospitals in a two-year period. Antimicrobial resistance patterns were confirmed with the broth dilution method. Evaluation of KPC, VIM, NDM, IMP, and OXA-48-like enzymes was performed and compared to NG-Test CARBA 5 and phenotypic assays. Enterobacterales represented 69% of isolates and P. aeruginosa represented 31%. Carbapenemase-producing strains were 51 (88%) of Enterobacterales and 23 (88.4%) of P. aeruginosa; 20 (34%) and 23 (88%) were Class B ß-lactamases, respectively. The NG-Test CARBA 5® assay for Enterobacterales showed high sensitivity (98%), specificity (100%), and PPV (100%); however, it did not for P. aeruginosa. The Kappa concordance coefficient was 0.92 for Enterobacterales and 0.52 for P. aeruginosa. NG-Test CARBA 5® is a fast and easy-to-use assay. In Enterobacterales, we found excellent agreement in our comparison with molecular tests. Despite the low agreement in P. aeruginosa, we suggest that this test could be used as a complementary tool.

Acquired blaVIM and blaGES Carbapenemase-Encoding Genes in Pseudomonas aeruginosa: A Seven-Year Survey Highlighting an Increasing Epidemiological Threat.

(1) Background: Pseudomonas aeruginosa is a Gram-negative bacterium with several intrinsic and acquired antimicrobial resistance mechanisms. The spread of carbapenemase-encoding genes, an acquired mechanism, enables carbapenem resistance in clinical settings. Detection of the carbapenemase-producer strains is urgent. Therefore, we aimed to characterize carbapenemase production in the clinical strains of P. aeruginosa at a tertiary-care center. (2) Methods: We included clinical strains of P. aeruginosa (from August 2011 to December 2018) with resistance towards at least one carbapenem. Strains were isolated in a tertiary-care center in Mexico City. Antimicrobial susceptibility profiles were determined by broth microdilution. Screening for carbapenemase-encoding genes was performed in all strains. Phenotypic assays (CarbaNP and mCIM) were conducted. Additional modifications to mCIM were also tested. (3) Results: One-hundred seventy-one P. aeruginosa strains out of 192 included in this study were resistant towards at least one of the carbapenems tested. Forty-seven of these strains harbored a carbapenemase-encoding gene. VIM (59.6%) and GES (23.4%) were the most frequently found carbapenemases in our study, followed by IMP (14.9%). (4) Among the most frequent carbapenemase genes identified, metallo-ß-lactamases were the most prevalent, which impair new treatment options. Searching for carbapenemase genes should be performed in resistant isolates to stop transmission and guide antimicrobial treatment.

Resistance against two lytic phage variants attenuates virulence and antibiotic resistance in Pseudomonas aeruginosa.

Background: Bacteriophage therapy is becoming part of mainstream Western medicine since antibiotics of clinical use tend to fail. It involves applying lytic bacteriophages that self-replicate and induce cell lysis, thus killing their hosts. Nevertheless, bacterial killing promotes the selection of resistant clones which sometimes may exhibit a decrease in bacterial virulence or antibiotic resistance. Methods: In this work, we studied the Pseudomonas aeruginosa lytic phage φDCL-PA6 and its variant φDCL-PA6α. Additionally, we characterized and evaluated the production of virulence factors and the virulence in a Galleria mellonella model of resistant mutants against each phage for PA14 and two clinical strains. Results: Phage φDCL-PA6α differs from the original by only two amino acids: one in the baseplate wedge subunit and another in the tail fiber protein. According to genomic data and cross-resistance experiments, these changes may promote the change of the phage receptor from the O-antigen to the core lipopolysaccharide. Interestingly, the host range of the two phages differs as determined against the Pseudomonas aeruginosa reference strains PA14 and PAO1 and against nine multidrug-resistant isolates from ventilator associated pneumonia. Conclusions: We show as well that phage resistance impacts virulence factor production. Specifically, phage resistance led to decreased biofilm formation, swarming, and type III secretion; therefore, the virulence towards Galleria mellonella was dramatically attenuated. Furthermore, antibiotic resistance decreased for one clinical strain. Our study highlights important potential advantages of phage therapy's evolutionary impact that may be exploited to generate robust therapy schemes.

Implication of myddosome complex genetic variants in outcome severity of COVID-19 patients.

BACKGROUND/PURPOSE(S): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. METHODS: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. RESULTS: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21-4.9) with deceased outcomes. CONCLUSION: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

Whole genome analysis of Gram-negative bacteria using the EPISEQ CS application and other bioinformatic platforms.

OBJECTIVES: To determine genomic characteristics and molecular epidemiology of carbapenem non-susceptible Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa from medical centres of Mexico using whole genome sequencing data analysed with the EPISEQⓇ CS application and other bioinformatic platforms. METHODS: Clinical isolates collected from 28 centres in Mexico included carbapenem-non-susceptible K. pneumoniae (n = 22), E. coli (n = 24), A. baumannii (n = 16), and P. aeruginosa (n = 13). Isolates were subjected to whole genome sequencing using the Illumina (MiSeq) platform. FASTQ files were uploaded to the EPISEQⓇ CS application for analysis. Additionally, the tools Kleborate v2.0.4 and Pathogenwatch were used as comparators for Klebsiella genomes, and the bacterial whole genome sequence typing database was used for E. coli and A. baumannii. RESULTS: For K. pneumoniae, both bioinformatic approaches detected multiple genes encoding aminoglycoside, quinolone, and phenicol resistance, and the presence of blaNDM-1 explained carbapenem non-susceptibility in 18 strains and blaKPC-3 in four strains. Regarding E. coli, both EPISEQⓇ CS and bacterial whole genome sequence typing database analyses detected multiple virulence and resistance genes: 20 of 24 (83.3%) strains carried blaNDM, 3 of 24 (12.4%) carried blaOXA-232, and 1 carried blaOXA-181. Genes that confer resistance to aminoglycosides, tetracyclines, sulfonamides, phenicols, trimethoprim, and macrolides were also detected by both platforms. Regarding A. baumannii, the most frequent carbapenemase-encoding gene detected by both platforms was blaOXA-72, followed by blaOXA-66. Both approaches detected similar genes for aminoglycosides, carbapenems, tetracyclines, phenicols, and sulfonamides. Regarding P. aeruginosa, blaVIM, blaIMP, and blaGES were the more frequently detected. Multiple virulence genes were detected in all strains. CONCLUSION: Compared to the other available platforms, EPISEQⓇ CS enabled a comprehensive resistance and virulence analysis, providing a reliable method for bacterial strain typing and characterization of the virulome and resistome.

Active Surveillance of Antimicrobial Resistance and Carbapenemase-Encoding Genes According to Sites of Care and Age Groups in Mexico: Results from the INVIFAR Network.

We analyzed the antimicrobial resistance (AMR) data of 6519 clinical isolates of Escherichia coli (n = 3985), Klebsiella pneumoniae (n = 775), Acinetobacter baumannii (n = 163), Pseudomonas aeruginosa (n = 781), Enterococcus faecium (n = 124), and Staphylococcus aureus (n = 691) from 43 centers in Mexico. AMR assays were performed using commercial microdilution systems (37/43) and the disk diffusion susceptibility method (6/43). The presence of carbapenemase-encoding genes was assessed using PCR. Data from centers regarding site of care, patient age, and clinical specimen were collected. According to the site of care, the highest AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from ICU patients. In contrast, in A. baumannii, higher AMR was observed in isolates from hospitalized non-ICU patients. According to age group, the highest AMR was observed in the ≥60 years age group for E. coli, E. faecium, and S. aureus, and in the 19-59 years age group for A. baumannii and P. aeruginosa. According to clinical specimen type, a higher AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from blood specimens. The most frequently detected carbapenemase-encoding gene in E. coli was blaNDM (84%).

Ocular Surface Characteristics and Colonization in a Burn Center: A Prospective Cohort Study.

We aimed to evaluate the characteristics and colonization by pathogenic microorganisms of the ocular surface in patients in a burn center and to determine their association with sedation, mechanical ventilation, and periocular burn. We prospectively evaluated 40 patients during an 8-mo period. Five evaluations where performed, at baseline and weekly on four more occasions or until hospital discharge or death. On each visit, we assessed periocular burn, lid position, Bell's phenomenon, Schirmer's test, presence of chemosis, conjunctival hyperemia, and exposure keratopathy; conjunctival fornix swabs were taken for microbiology culture. Also, we documented the level of sedation, mechanical ventilation status, and systemic and ocular treatment. Absent Bell's phenomenon and chemosis were significantly different at baseline in patients under mechanical ventilation, sedation, and in those with a periocular burn. The cumulative incidence of exposure keratopathy was 22.5% and the cumulative incidence of ocular surface colonization by pathogenic microorganisms was 32.5%. Both outcomes were associated with mechanical ventilation and periocular burn. The most frequent pathogenic microorganisms on the ocular surface were Candida parapsilosis, Acinetobacter baumanii, and Pseudomonas aeuroginosa. We did not observe any case of a persistent epithelial defect, infectious keratitis, corneal perforation or corneal opacity in this cohort. Results from our study may benefit future patients by allowing better risk stratification and treatment strategies for the ocular surface care in burn units.

Emergence of Fosfomycin Resistance by Plasmid-Mediated fos Genes in Uropathogenic ESBL-Producing E. coli Isolates in Mexico.

Fosfomycin is currently a viable option against urinary tract infections, particularly against extended-spectrum ß-lactamases (ESBL)-producing E. coli, due to its unique mechanism of action and its low resistance among bacteria. The objective of this study was to investigate two of the three most common mechanisms of resistance against this antibiotic among 350 ESBL-producing E. coli strains isolated from the urine of Mexican patients. The prevalence of fosfomycin resistance in our study was 10.9% (38/350). Of all resistant isolates analyzed, 23 (60.5%) were identified as fos-producing organisms, with 14 strains carrying fosA3 and 9, fosA1. Additionally, 11 (28.9%) fosfomycin-resistant isolates presented resistance due to impaired antibiotic transport and 8 (21.0%) both mechanisms. No resistance mechanism investigated in the study was found on 12 strains. All 38 confirmed ESBL-producing isolates carried a blaCTX-M subtype, 36 (94.5%) belonged to the O25b-ST131 clone, and all of them were able to transfer the fosfomycin resistance trait to recipient strains horizontally. This is the first study in Mexico demonstrating a plasmid-mediated fosfomycin resistance mechanism among clinical E. coli strains. Since our results suggest a strong association among fos and blaCTX-M genes and ST131 clones in uropathogenic E. coli, plasmid-mediated fosfomycin resistance should be closely monitored.

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01-3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01-3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10-2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

Increment Antimicrobial Resistance During the COVID-19 Pandemic: Results from the Invifar Network.

Aim: This study aims to assess the changes in antimicrobial resistance among some critical and high-priority microorganisms collected previously and during the coronavirus disease 2019 (COVID-19) pandemic in Mexico. Methods: We collected antimicrobial susceptibility data for critical and high-priority microorganisms from blood, urine, respiratory samples, and from all specimens, in which the pathogen may be considered a causative agent. Data were stratified and compared for two periods: 2019 versus 2020 and second semester 2019 (prepandemic) versus the second semester 2020 (pandemic). Results: In the analysis of second semester 2019 versus the second semester 2020, in blood samples, increased resistance to oxacillin (15.2% vs. 36.9%), erythromycin (25.7% vs. 42.8%), and clindamycin (24.8% vs. 43.3%) (p ≤ 0.01) was detected for Staphylococcus aureus, to imipenem (13% vs. 23.4%) and meropenem (11.2% vs. 21.4) (p ≤ 0.01), for Klebsiella pneumoniae. In all specimens, increased ampicillin and tetracycline resistance was detected for Enterococcus faecium (p ≤ 0.01). In cefepime, meropenem, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Escherichia coli; and in piperacillin-tazobactam, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Pseudomonas aeruginosa. Conclusion: Antimicrobial resistance increased in Mexico during the COVID-19 pandemic. The increase in oxacillin resistance for S. aureus and carbapenem resistance for K. pneumoniae recovered from blood specimens deserves special attention. In addition, an increase in erythromycin resistance in S. aureus was detected, which may be associated with high azithromycin use. In general, for Acinetobacter baumannii and P. aeruginosa, increasing resistance rates were detected.