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.

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.

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.

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%).

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.

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.

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.

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.

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.

Hipoacusia en pacientes con y sin COVID-19 antes y después de la recuperación de los casos positivos / Hearing loss in patients with and without COVID-19 before and after recovery from positive cases

Introducción y objetivo: Aun son pocos los estudios sobre el daño de la COVID-19 en la audición por lo que se recomienda evaluaciones iniciales y su seguimiento, el objetivo de este estudio fue comparar el grado y tipo de hipoacusia en sujetos con y sin COVID-19 al inicio del padecimiento y después de su recuperación de quienes se confirmó su positividad. Método: Estudio prospectivo, comparativo no experimental. Previa firma del consentimiento informado a una muestra voluntaria de 105 sujetos que acudieron a confirmar positividad a COVID-19 se les realizo audiometría tonal y una revaloración posterior a su recuperación de los positivos Resultados: la hipoacusia superficial sensorial fue más frecuente en el grupo de 35 a 50 años, en el grupo negativo a SARS-Cov-2, los resultados antes-después de la recuperación de los positivos fue significativa en el promedio de 7 frecuencias y frecuencias medias. Discusión: Los resultados de este estudio coinciden con lo publicado en relación con el tipo y grado de hipoacusia, la edad y la no percepción de esta, la diversidad de síntomas de COVID-19 sin diferencias entre los grupos con y sin COVID-19. Las diferencias en los promedios de tonos puros en 7 frecuencias y frecuencias medias no reportadas para el contraste. Conclusiones: el tipo y grado de hipoacusia fue el esperado con respecto a la edad, las diferencias en los promedios antes y después fueron mejores en la segunda evaluación probablemente por la resolución del cuadro inflamatorio. Se recomienda aumentar la muestra y agregar evaluación objetiva de oído medio. (AU)

Introduction and objective: There are still few studies on the damage of COVID-19 in hearing, so initial evaluations and their follow-up are recommended, the objective of this study was to compare the degree and type of hearing loss in subjects with and without COVID-19 at the beginning of the disease and after their recovery of whom their positivity was confirmed. Method: prospective, compa-rative non-experimental study. After signing the informed consent to a voluntary sample of 105 subjects who came to confirm positivity for COVID-19, they underwent tonal audiometry and a reassessment after their recovery of the positives. Results: Sensory superficial hearing loss was more frequent in the group aged 35 to 50 years, in the group negative to SARS-Cov-2, the results before-after the recovery of the positive ones was significant in the average of 7 frequencies and medium frequencies. Discussion: The results of this study coincide with what has been published in relation to the type and degree of hearing loss, age and non-perception of it, the diversity of COVID-19 symptoms without differences between the groups with and without COVID-19. Differences in the averages of pure tones at 7 frequencies and mid-frequencies not reported for contrast. Conclusions: the type and degree of hearing loss was as expected with respect to age, the differences in the averages before and after were better in the second evaluation, probably due to the resolution of the inflammatory condition. It is recommended to increase the sample and add an objective evaluation of the ear half. (AU)

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.

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.

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.

New prophylaxis regimen for SARS-CoV-2 infection in health professionals with low doses of hydroxychloroquine and bromhexine: a randomised, double-blind placebo clinical trial (ELEVATE Trial).

INTRODUCTION: SARS-CoV-2 infection in Mexico has caused ~2.7 million confirmed cases; around 20%-25% of health workers will be infected by the virus at their workplace, with approximately 4.4% of mortality. High infectivity of SARS-CoV-2 is related with cell entry mechanism, through the ACE receptor. SARS-CoV-2 requires transmembrane protease serine 2 to cleave its spike glycoprotein and ensure fusion of host cell and virus membrane. We propose studying prophylactic treatment with hydroxychloroquine (HCQ) and bromhexine (BHH), which have been shown to be effective in preventing SARS-CoV-2 infection progression when administered in early stages. The aim of this study is to assess the efficacy of HCQ and BHH as prophylactic treatments for SARS-CoV-2 infection in healthy health workers exposed to the virus. METHODS AND ANALYSIS: Double-blind randomised clinical trial, with parallel allocation at a 1:1 ratio with placebo, of low doses of HCQ plus BHH, for 60 days. Study groups will be defined as follows: (1) HCQ 200 mg/day+BHH 8 mg/8 hours versus (2) HCQ placebo plus BHH placebo. Primary endpoint will be efficacy of both interventions for the prevention of SARS-CoV-2 infection, determined by the risk ratio of infected personnel and the absolute risk. At least a 16% reduction in absolute risk is expected between the intervention and placebo groups; a minimum of 20% infection is expected in the placebo group. The sample size calculation estimated a total of 214 patients assigned: two groups of 107 participants each. ETHICS AND DISSEMINATION: This protocol has been approved by the local Medical Ethics Committee (National Institute of Rehabilitation 'Luis Guillermo Ibarra Ibarra', approval number INRLGII/25/20) and by the Federal Commission for Protection against Sanitary Risks (COFEPRIS, approval number 203 300 410A0058/2020). The results of the study will be submitted for publication in peer-reviewed journals and disseminated through conferences. TRIAL REGISTRATION NUMBER: NCT04340349.

Serological prevalence of SARS-CoV-2 infection and associated factors in healthcare workers in a "non-COVID" hospital in Mexico City.

BACKGROUND: Mexico is one of the countries with the highest number of deaths from the COVID-19 pandemic. In spite of this high mortality, in Mexico the number of confirmed cases and diagnostic tests per million population are lower than for other comparable countries, which leads to uncertainty about the actual extent of the pandemic. In Mexico City, healthcare workers represent an important fraction of individuals with SARS-CoV-2 infection. We performed a cross-sectional study whose objective was to estimate the frequency of antibodies to SARS-CoV-2 and identify associated factors in healthcare workers at a large hospital in Mexico City. METHODS: We conducted a serological survey in a non-COVID national referral teaching hospital. The study population included all the personnel that works, in any capacity, in the hospital. From this population we selected a representative sample of 300 individuals. Blood samples were collected and questionnaires were applied between August 10th and September 9th, 2020. RESULTS: ELISA results indicate a serological prevalence of SARS-CoV-2 infection of 13.0%. Working in the janitorial and security groups, having an educational level below a university degree, and living with a larger number of people, were all identified as sociodemographic factors that increase the probability of having SARS-CoV-2 infection. CONCLUSIONS: Less favored socioeconomic groups face significantly higher prospects of experiencing SARS-CoV-2 infection and in institutions such as ours, providing janitorial and security workgroups with additional testing and counseling could help to limit the spread of contagion. The rate from the official number of confirmed cases in Mexico City is substantially smaller than the seropositive rate identified in this work.

Staphylococcus epidermidis small colony variants, clinically significant quiescent threats for patients with prosthetic joint infection.

OBJECTIVES: Staphylococcus epidermidis is a leading cause of prosthetic joint infection. Its relevance is based on its high ability to develop biofilm and small colony variants. However, the clinical associations between this bacterial subpopulation and prosthetic joint infections remain highly uncertain. We aimed to define the clinical characteristics and outcome of patients affected by S. epidermidis small colony variants, as well as their antimicrobial susceptibility. METHODS: We conducted a retrospective cohort study of patients with monomicrobial prosthetic joint infection. Clinical data and time to remission after prosthesis removal was compared between groups. Antimicrobial susceptibility of small colony variants and wild type strains were analyzed. RESULTS: S. epidermidis small colony variants were identified in 16 (37.20%) cultures from eligible subjects. These patients were less likely to achieve remission throughout the follow-up period (Hazard ratio, 0.45 [95% CI, 0.22-0.89], p=0.02), compared to those with wild type strains. In vitro experiments showed higher resistant rates to trimethoprim/sulfamethoxazole (62.5%), and lower resistant rates to levofloxacin (37.5%), among small colony variants. CONCLUSIONS: The isolation of small colony variants was negatively associated with remission achievement throughout management. The search for this bacterial subpopulation and its antimicrobial susceptibility may be appropriate to adjust treatment and clinical expectations.

Probable Case of Vertical Transmission of SARS-CoV-2 in a Newborn in Mexico.

BACKGROUND: Much remains unknown about the transmission of the SARS-CoV-2 virus. Pregnant women are considered part of the risk population, and vertical transmission of other coronaviruses has been suggested; however, this type of transmission in SARS-CoV-2 is believed to be unlikely. CASE REPORT: A newborn delivered in term via cesarean section to an asymptomatic but COVID-19-positive 35-year-old woman started with respiratory distress in the first 30 min of life. A chest radiograph revealed pneumothorax and ground glass opacities. Ventilatory support with continuous positive airway pressure was needed. Given the respiratory failure and the positive test from the mother, the patient was sampled for SARS-CoV-2 (RT-PCR) at minute 30 of life, with a positive result reported at 36 h of life. No complications had been present during pregnancy, and cardiac screening and blood cultures revealed no other etiologies. CONCLUSION: Vertical transmission was highly likely in this case. Clinicians should be alert and report similar cases.

Drug resistance phenotypes and genotypes in Mexico in representative gram-negative species: Results from the infivar network.

AIM: This report presents phenotypic and genetic data on the prevalence and characteristics of extended-spectrum ß-lactamases (ESBLs) and representative carbapenemases-producing Gram-negative species in Mexico. MATERIAL AND METHODS: A total of 52 centers participated, 43 hospital-based laboratories and 9 external laboratories. The distribution of antimicrobial resistance data for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, Acinetobacter baumannii complex, and Pseudomonas aeruginosa in selected clinical specimens from January 1 to March 31, 2020 was analyzed using the WHONET 5.6 platform. The following clinical isolates recovered from selected specimens were included: carbapenem-resistant Enterobacteriaceae, ESBL or carbapenem-resistant E. coli, and K. pneumoniae, carbapenem-resistant A. baumannii complex, and P. aeruginosa. Strains were genotyped to detect ESBL and/or carbapenemase-encoding genes. RESULTS: Among blood isolates, A. baumannii complex showed more than 68% resistance for all antibiotics tested, and among Enterobacteria, E. cloacae complex showed higher resistance to carbapenems. A. baumannii complex showed a higher resistance pattern for respiratory specimens, with only amikacin having a resistance lower than 70%. Among K. pneumoniae isolates, blaTEM, blaSHV, and blaCTX were detected in 68.79%, 72.3%, and 91.9% of isolates, respectively. Among E. coli isolates, blaTEM, blaSHV, and blaCTX were detected in 20.8%, 4.53%, and 85.7% isolates, respectively. For both species, the most frequent genotype was blaCTX-M-15. Among Enterobacteriaceae, the most frequently detected carbapenemase-encoding gene was blaNDM-1 (81.5%), followed by blaOXA-232 (14.8%) and blaoxa-181(7.4%), in A. baumannii was blaOXA-24 (76%) and in P. aeruginosa, was blaIMP (25.3%), followed by blaGES and blaVIM (13.1% each). CONCLUSION: Our study reports that NDM-1 is the most frequent carbapenemase-encoding gene in Mexico in Enterobacteriaceae with the circulation of the oxacillinase genes 181 and 232. KPC, in contrast to other countries in Latin America and the USA, is a rare occurrence. Additionally, a high circulation of ESBL blaCTX-M-15 exists in both E. coli and K. pneumoniae.