Predictors of Mortality in Patients with Infections Due to Carbapenem-Resistant Gram-Negative Bacteria.

INTRODUCTION: Infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) are a significant cause of mortality and represent a serious challenge to health systems. The early identification of mortality predictors could guide appropriate treatment and follow-up. We aimed to identify the factors associated with 90-day all-cause mortality in patients with CR-GNB infections. METHODS: We conducted a cohort study from 1 January 2019 to 30 April 2022. The primary outcome was death from any cause during the first 90 days after the date of the first CR-GNB-positive culture. Secondary outcomes included infection relapse, invasive mechanical ventilation during follow-up, need for additional source control, acute kidney injury, Clostridioides difficile infection, and all-cause hospital admission after initial discharge. Bivariate and multivariate Cox-proportional hazards models were constructed to identify the factors independently associated with 90-day all-cause mortality. RESULTS: A total of 225 patients with CR-GNB infections were included. Death occurred in 76 (34%) cases. The most-reported comorbidities were immunosuppression (43%), arterial hypertension (35%), and COVID-19 (25%). The median length of stay in survivors was 18 days (IQR 10-34). Mechanical ventilation and ICU admission after diagnosis occurred in 8% and 11% of cases, respectively. Both infection relapse and rehospitalisation occurred in 18% of cases. C. difficile infection was diagnosed in 4% of cases. Acute kidney injury was documented in 22% of patients. Mechanical ventilation after diagnosis, ICU admission after diagnosis, and acute kidney injury in the first ten days of appropriate treatment were more frequently reported among non-survivors. In the multivariate analysis, age (HR 1.19 (95%CI 1.00-1.83)), immunosuppression (HR 1.84 (95%CI 1.06-3.18)), and septic shock at diagnosis (HR 2.40 (95% 1.41-4.08)) had an independent association with death during the first 90 days after the CR-GNB infection diagnosis. Receiving antibiogram-guided appropriate treatment was independently associated with a lower risk of death (HR 0.25 (95%CI 0.14-0.46)). CONCLUSIONS: The presence of advanced age, immunosuppression, septic shock at diagnosis, and inappropriate treatment are associated with higher 90-day all-cause mortality in hospitalised patients with infections due to CR-GNB. Recognition of the risk factors for adverse outcomes could further assist in patient care and the design of interventional studies that address the severe and widespread problem that is carbapenem resistance.

Multiple Brain Abscesses Caused by Nocardia Beijingensis in a Patient With HIV Infection.

The etiologic agents of central nervous system infections in HIV-infected patients comprise a broad range of opportunistic pathogens. We presented a 49-year-old male patient with HIV infection and low adherence to antiretroviral therapy. He presented with multiple cerebral abscesses, and his microbiological diagnosis approach resulted in the isolation of Nocardia beijingensis , a species rarely reported in America. Central nervous system nocardial infection in HIV-infected patients should be considered, and a diagnosis at species level is mandatory because the antibiotic susceptibility profile varies among species.

Outbreak of NDM-1-Producing Escherichia coli in a Coronavirus Disease 2019 Intensive Care Unit in a Mexican Tertiary Care Center.

Emergency department areas were repurposed as intensive care units (ICUs) for patients with acute respiratory distress syndrome during the initial months of the coronavirus disease 2019 (COVID-19) pandemic. We describe an outbreak of New Delhi metallo-ß-lactamase 1 (NDM-1)-producing Escherichia coli infections in critically ill COVID-19 patients admitted to one of the repurposed units. Seven patients developed infections (6 ventilator-associated pneumonia [VAP] and 1 urinary tract infection [UTI]) due to carbapenem-resistant E. coli, and only two survived. Five of the affected patients and four additional patients had rectal carriage of carbapenem-resistant E. coli. The E. coli strain from the affected patients corresponded to a single sequence type. Rectal screening identified isolates of two other sequence types bearing blaNDM-1. Isolates of all three sequence types harbored an IncFII plasmid. The plasmid was confirmed to carry blaNDM-1 through conjugation. An outbreak of clonal NDM-1-producing E. coli isolates and subsequent dissemination of NDM-1 through mobile elements to other E. coli strains occurred after hospital conversion during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This emphasizes the need for infection control practices in surge scenarios. IMPORTANCE The SARS-CoV-2 pandemic has resulted in a surge of critically ill patients. Hospitals have had to adapt to the demand by repurposing areas as intensive care units. This has resulted in high workload and disruption of usual hospital workflows. Surge capacity guidelines and pandemic response plans do not contemplate how to limit collateral damage from issues like hospital-acquired infections. It is vital to ensure quality of care in surge scenarios.

Tracheal Aspirate Galactomannan Testing in COVID-19-Associated Pulmonary Aspergillosis.

Among critically ill patients, COVID-19-associated pulmonary aspergillosis (CAPA) is a challenging complication. The recommended diagnostic methods for this disease are bronchoalveolar lavage (BAL) culture and galactomannan (GM) testing, which were not widely available during the pandemic. There is scarce information regarding GM testing in other respiratory specimens. Our objective was to compare the agreement of GM between BAL and tracheal aspirate (TA) samples. We selected patients with COVID-19 and those with suspected CAPA who were admitted in the intensive care unit (ICU). GM was routinely done in BAL. We performed GM in TA samples and compared the results. The agreement was evaluated with Cohen's Kappa coefficient. GM was considered positive when an OD index ≥ 1 in BAL and ≥ 2 in TA were found. Probable CAPA was considered when the ECMM/ISHAM criteria were met. A descriptive analysis of clinical characteristics and mortality was made. We included 20 patients with suspected CAPA from 54 patients with critical COVID-19, of which 5 (9%) met the probable category. Aspergillus fumigatus was the most frequent isolate. We found moderate agreement between BAL and TA GM (Kappa = 0.47, p = 0.01, 95% CI.04-0.9), whereas TA GM had 75% sensitivity (95% CI 19.4-99.4%), 81.2% specificity (95% CI 54.4-95.9%), 50% positive predictive value (95% CI 23.8-76.3%),] and 92.8% negative predictive value (95% CI 70.1-98.6%), and 80% accuracy (95% CI 56.3-94.3%). Lastly, three (60%) patients with CAPA died during hospitalization compared to 40% (6/15) without CAPA (p = 0.4). In conclusion, a moderate agreement between TA GM and BAL was found. Therefore, TA testing may aid in ruling out CAPA due to high negative predictive value when bronchoscopies are unavailable.

Isolation of Rhizopus microsporus and Lichtheimia corymbifera from tracheal aspirates of two immunocompetent critically ill patients with COVID-19.

We describe two fatal cases of COVID-19 in which Rhizopus microsporus and Lichtheimia corymbifera were cultured from endotracheal aspirate samples. Both patients had no underlying comorbidities other than obesity. Despite antifungal therapy, both cases developed septic shock and progressive refractory hypoxemia without evidence of other underlying infections. It is unclear whether isolation of these fungal organisms represents invasive disease or corresponds to an epiphenomenon of critical illness. Yet, patients suffering from COVID-19 may be at risk of superinfection from a broader range of fungal organisms than previously thought.

Inhibitors of DNA topoisomerases I and II applied to Candida dubliniensis reduce growth, viability, the generation of petite mutants and toxicity, while acting synergistically with fluconazole.

The increasing resistance of Candida species to azoles emphasizes the urgent need for new antifungal agents with novel mechanisms of action. The aim of this study was to examine the effect of three DNA topoisomerase inhibitors of plant origin (camptothecin, etoposide and curcumin) on the growth of Candida dubliniensis. The phylogenetic analysis showed a close relationship between the topoisomerase enzymes of C. dubliniensis and Candida albicans. The alignment of the amino acid sequences of topoisomerase I and II of yeasts and humans evidenced conserved domains. The docking study revealed affinity of the test compounds for the active site of topoisomerase I and II in C. dubliniensis. Curcumin and camptothecin demonstrated a stronger in vitro antifungal effect than the reference drugs (fluconazole and itraconazole). Significant synergistic activity between the topoisomerase inhibitors and fluconazole at the highest concentration (750 µM) was observed. Fluconazole induced the petite phenotype to a greater degree than the topoisomerase inhibitors, indicating a tendency to generate resistance. Lower toxicity was found for such inhibitors versus reference drugs on Galleria mellonella larva. The topoisomerase inhibitors exhibited promising antifungal activity, and the DNA topoisomerase enzymes of C. dubliniensis proved to be an excellent model for evaluating new antifungal compounds.

Thoracic actinomycetoma: a retrospective clinical-epidemiological study of 64 cases.

BACKGROUND: Actinomycetoma is a chronic granulomatous infection that follows traumatic implantation. Thoracic actinomycetoma (TA) is rare and may lead to severe complications. METHODS: A retrospective study of cases of TA diagnosed from 1985 to 2019 was carried out. Each case underwent direct examination, culture and biopsy. RESULTS: Sixty-four cases (12.8%) were included, with a male predominance (84.3%); the main occupation was peasant farmer (71.8%) and the main site was the back (76.5%). Vertebral involvement was observed in 21.8% and pulmonary involvement in 7.8%. Nocardia brasiliensis was the main aetiological agent (53 cases, 74.5%). CONCLUSIONS: TA is a poorly studied disease that can cause neurological and lung complications.

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico.

BACKGROUND: The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. METHODOLOGY/PRINCIPAL FINDINGS: We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78-30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4-76.2) / 96.2% (95% CI, 93.2-98.0) for IAHE, 91.3% (95% CI, 84.2-96.0) / 90.9% (95% CI, 87.0-94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0-95.3) / 92.3% (95% CI, 88.6-95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3-72.5)/ 89.5% (95%CI, 86.0-93.0), 65.9% (95%CI, 56.0-75.8)/ 89.0% (95%CI, 85.2-92.9), 62.1% (95%CI, 44.4-79.7)/ 82.6% (95%CI, 71.7-93.6) and 34.9% (95%CI, 24.8-46.2)/ 67.3% (95%CI, 60.6-73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9-74.7)/ 58.8% (95%CI, 53.2-64.5), 70.8% (95%CI, 61.3-80.2)/ 52.9% (95%CI, 46.8-59.1), 71.4% (95%CI, 54.7-88.2)/ 40.4% (95%CI, 26.4-54.5) and 18.1% (95%CI, 10.5-28.1)/ 90.4% (95%CI, 85.5-94.0), respectively. CONCLUSIONS/SIGNIFICANCE: The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

Antimicrobial Resistance Patterns and Antibiotic Use during Hospital Conversion in the COVID-19 Pandemic.

OBJECTIVE: To describe empirical antimicrobial prescription on admission in patients with severe COVID-19, the prevalence of Hospital-Acquired Infections, and the susceptibility patterns of the causing organisms. METHODS: In this prospective cohort study in a tertiary care center in Mexico City, we included consecutive patients admitted with severe COVID-19 between March 20th and June 10th and evaluated empirical antimicrobial prescription and the occurrence of HAI. RESULTS: 794 patients with severe COVID-19 were admitted during the study period. Empiric antibiotic treatment was started in 92% of patients (731/794); the most frequent regimes were amoxicillin-clavulanate plus atypical coverage in 341 (46.6%) and ceftriaxone plus atypical coverage in 213 (29.1%). We identified 110 HAI episodes in 74/656 patients (11.3%). Ventilator-associated pneumonia (VAP) was the most frequent HAI, in 56/110 (50.9%), followed by bloodstream infections (BSI), in 32/110 (29.1%). The most frequent cause of VAP were Enterobacteriaceae in 48/69 (69.6%), followed by non-fermenter gram-negative bacilli in 18/69 (26.1%). The most frequent cause of BSI was coagulase negative staphylococci, in 14/35 (40.0%), followed by Enterobacter complex in 7/35 (20%). Death occurred in 30/74 (40.5%) patients with one or more HAI episodes and in 193/584 (33.0%) patients without any HAI episode (p < 0.05). CONCLUSION: A high frequency of empiric antibiotic treatment in patients admitted with COVID-19 was seen. VAP and BSI were the most frequent hospital-acquired infections, due to Enterobacteriaceae and coagulase negative staphylococci, respectively.

Accuracy of galactomannan testing on tracheal aspirates in COVID-19-associated pulmonary aspergillosis.

OBJECTIVE: Our aim was to evaluate the performance of two galactomannan (GM) assays (Platelia Aspergillus EIA, Bio-Rad® , and Aspergillus GM LFA, IMMY® ) in tracheal aspirate (TA) samples of consecutive critically ill patients with COVID-19. METHODS: We included critically ill patients, performed GM-EIA and GM-Lateral Flow Assay (GM-LFA) in TA and followed them until development of COVID-19-associated pulmonary aspergillosis (CAPA) or alternate diagnosis. CAPA was defined according to the modified AspICU criteria in patients with SARS-CoV-2 infection. We estimated sensitivity, specificity, positive and negative predictive values for GM-EIA, GM-LFA, the combination of both or either positive results for GM-EIA and GM-LFA. We explored accuracy using different breakpoints, through ROC analysis and Youden index to identify the optimal cut-offs. We described antifungal treatment and 30-day mortality. RESULTS: We identified 14/144 (9.7%) patients with CAPA, mean age was 50.35 (SD 11.9), the median time from admission to CAPA was 8 days; 28.5% received tocilizumab and 30-day mortality was 57%. ROC analysis and Youden index identified 2.0 OD as the best cut-off, resulting in sensitivity and specificity of 57.1% and 81.5% for GM-EIA and 60% and 72.6% for GM-LFA, respectively. CONCLUSIONS: The diagnostic performance of GM in tracheal aspirates improved after using a cut-off of 2 OD. Although bronchoalveolar lavage testing is the ideal test, centres with limited access to bronchoscopy may consider this approach to identify or rule out CAPA.

Azole resistance and cyp51A mutation screening in Aspergillus fumigatus in Mexico.

BACKGROUND: Fungicide exposure in the environment has driven the emergence of azole-resistant Aspergillus fumigatus worldwide. A screening test allows identification of resistant isolates. OBJECTIVES: We screened clinical samples for azole-resistant Aspergillus through azole-containing agar plates and identified mutations in the cyp51A gene of A. fumigatus. METHODS: Aspergillus isolates from clinical samples collected in a tertiary care centre from 2014 to 2017 were screened for azole resistance. Samples were subcultured in azole-containing agar plates. Isolates with a positive screening test were subject to DNA extraction, DNA amplification and sequencing of the cyp51A gene (coding and promoter regions). Clinical data were obtained from medical records. RESULTS: We screened 43 Aspergillus isolates from 39 patients for azole resistance. Three isolates from three patients grew on azole-containing agar plates: two A. fumigatus and one Aspergillus flavus. PCR analysis and cyp51A sequencing identified the TR34/L98H mutation in both A. fumigatus isolates. The prevalence of cyp51A mutations among A. fumigatus was 8.3% (2/24). Both patients with TR34/L98H mutants were azole naive and presented with invasive aspergillosis; one had multiple myeloma and the other was a liver retransplant recipient. They suffered progressive disease and failed voriconazole therapy. CONCLUSIONS: To the best of our knowledge, this is the first report of azole-resistant A. fumigatus with the TR34/L98H mutation in two azole-naive patients with refractory invasive aspergillosis in Mexico.

Mycobacterium obuense Bacteremia in a Patient with Pneumonia.

Mycobacterium obuense is a pigmented, rapidly growing mycobacterium. Because it has been considered nonpathogenic, M. obuense is being investigated in clinical trials of cancer immunotherapy and bioremediation. We report a case of bacteremia caused by M. obuense in a patient with pneumonia, showing its potential pathogenicity.

Diagnostic accuracy cohort study and clinical value of the Histoplasma urine antigen (ALPHA Histoplasma EIA) for disseminated histoplasmosis among HIV infected patients: A multicenter study.

BACKGROUND: The Histoplasma urine antigen (HUAg) is the preferred method to diagnose progressive disseminated histoplasmosis (PDH) in HIV patients. In 2007, IMMY ALPHA Histoplasma EIA was approved for clinical for on-site use, and therefore useful for regions outside the United States. However, ALPHA-HUAg is considered inferior to the MVista-HUAg which is only available on referral. We aim to evaluate the diagnostic accuracy of ALPHA-HUAg. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multicenter, prospective, diagnostic test study in two secondary and eight tertiary-care facilities in Mexico. We included HIV patient with PDH suspicion and evaluated ALPHA-HUAg diagnostic accuracy using as reference standard the Histoplasma capsulatum growth on blood, bone marrow, and tissue cultures or compatible histopathologic exam (PDH-proven). We evaluated the results of 288 patients, 29.5% (85/288; 95% confidence interval [CI], 24.3-35.1) had PDH. The sensitivity of ALPHA-HUAg was 67.1% (95% CI, 56-76.8%) and the specificity was 97.5% (95% CI, 94.3%-99.1%). The positive likelihood ratio was 27.2 (95% CI; 11.6-74.4). In 10.5% of the PDH-proven patients, a co-existing opportunistic infection was diagnosed, mostly disseminated Mycobacterium avium complex infection. CONCLUSIONS/SIGNIFICANCE: We observed a high specificity but low sensitivity of IMMY-HUAg. The test may be useful to start early antifungals, but a culture-based approach is necessary since co-infections are frequent and a negative IMMY-HUAg result does not rule out PDH.

Antimicrobial susceptibility of gram-negative bacilli isolated from intra-abdominal and urinary-tract infections in Mexico from 2009 to 2015: Results from the Study for Monitoring Antimicrobial Resistance Trends (SMART).

Antimicrobial resistance is an increasing worldwide concern, which poses unique challenges for the effective prevention and treatment of several infections, especially the ones triggered by organisms producing extended-spectrum ß-lactamases (ESBL). Here, we present the surveillance results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) of Gram-negative bacilli isolated from intra-abdominal infections (IAI, n = 1,235) and urinary-tract infections (UTI, n = 2,682), collected in Mexico from 2009 to 2015. Susceptibility and ESBL status were determined according to the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Both E. coli (57%) and K. pneumoniae (12%) were the most frequently reported organisms, as well as the ones with the highest prevalence of ESBL-producing isolates (54% and 39%, respectively). The overall prevalence of ESBL-producing organisms was higher in nosocomial infections than in community-acquired infections (21% vs. 27%). The ESBL rates were 36% for IAI (953/2,682) and 37% for UTI (461/1,235). In addition, ertapenem, imipenem and amikacin were the antibiotics that mostly preserved bacterial susceptibility. Our results show consistency with global trends, although higher than the rates observed in Latin America.

Impact of inappropriate antifungal therapy according to current susceptibility breakpoints on Candida bloodstream infection mortality, a retrospective analysis.

BACKGROUND: The mortality of Candida Bloodstream Infection (CBSI) remains high. Antifungal susceptibility breakpoints were recently updated for Candida species, the impact remains unknown. In this study we evaluated the impact of inappropriate antifungal treatment according to recent breakpoints on 30-day mortality of CBSI. METHODS: From June 2008 to July 2014, data on CBSI episodes from two tertiary-care centers, treated > 72 h were analyzed. Antifungal therapy and 30-day mortality were registered. Inappropriate antifungal treatment according to current Clinical & Laboratory Standards Institute (CLSI) breakpoints was adjusted with 30-day mortality-related co-variates. RESULTS: One hundred forty-nine episodes of CBSI were analyzed. The most frequent species were: C. albicans (40%), C. tropicalis (23%) and C. glabrata complex (20%). According to the 2012 CLSI, 10.7% received inappropriate treatment. The 30-day mortality was 38%; severe sepsis [Odds ratio (OR) 3.4; 95% CI 1.3-8.4], cirrhosis (OR 36; 95% CI 12.2-605), early central venous catheter removal (OR 0.23; 95% CI 0.08-0.66) and previous antifungal therapy (OR 0.15; 95%CI 0.03-0.62), were associated with 30-day mortality by multivariate analysis. Inappropriate antifungal treatment was not (OR 0.19; 95% CI 0.03-1.2). CONCLUSIONS: Appropriate antifungal therapy according to CLSI 2012 did not have an impact on mortality. Mortality of CBSI remains high due to disease severity and comorbidities; early antifungal therapy and catheter removal may reduce it.

Identification and susceptibility testing of Candida spp. directly from yeast-positive blood cultures with Vitek 2.

Culture-based identification and antifungal susceptibility take 48-72hours after positivity. We analyzed the performance of Vitek2 directly from 40 yeast-positive blood-cultures; agreement of 100% was observed for the tested antifungals; identification showed the same species in 31/40. The method reduces time (13 to 18h) for preliminary results.

Human tuberculosis caused by Mycobacterium bovis: a retrospective comparison with Mycobacterium tuberculosis in a Mexican tertiary care centre, 2000-2015.

BACKGROUND: Human tuberculosis caused by Mycobacterium bovis is believed to be frequent in developing countries. Transmission is usually through ingestion of unpasteurized dairy products, although airborne contagion is possible. Disease caused by M. tuberculosis or M. bovis is clinically indistinguishable from each other. The aim of this study was to determine the factors associated with M. bovis disease. METHODS: Retrospective analysis of all culture-positive cases of M. bovis and M. tuberculosis from 2000 to 2015, in a Mexican tertiary-care centre. Sociodemographic, clinical, and radiographic data from medical records were compared. Disease site was classified as pulmonary, extrapulmonary, or pulmonary and extrapulmonary, based on cultures. RESULTS: We evaluated 533 cases, 372 (69.7 %) of which were caused by M. tuberculosis and 161 (30.2 %) by M. bovis. Characteristics associated with M. bovis disease were: younger age (aOR 0.97, 95 % CI 0.95-0.98), glucocorticoid use (aOR 2.27, 95 % CI 1.42-3.63), and extrapulmonary disease (aOR 1.80, 95 % CI 1.21-2.69). M. tuberculosis was associated with lower socioeconomic status (aOR 0.52, 95 % CI 0.28-0.97). When we analysed only pulmonary cases, younger age (aOR 0.97, 95 % CI 0.96-0.99), glucocorticoid use (aOR 2.41, 95 % CI 1.30-4.46), and smoking (aOR 1.94, CI 95 % 1.15-3.27) were associated with M. bovis. Both groups showed similar proportions of direct microscopy smear results (respiratory samples) and chest X-ray cavitations. CONCLUSIONS: Younger age, glucocorticoid use, and extrapulmonary disease were associated with M. bovis as the causative agent of tuberculosis in a group of patients from a tertiary care centre in a country where bovine tuberculosis is endemic. Further studies must be conducted in the general population to determine pathogen-specific associated factors and outcomes.

Associated factors and outcomes for OXA-232 Carbapenem-resistant Enterobacteriaceae infections in a tertiary care centre in Mexico City: A case-control-control study.

We describe the outcomes and factors associated with OXA-232 producing carbapenem-resistant Enterobacteriaceae infections. A case-control-control study was performed; each case of infection by a carbapenem-resistant/OXA-232 (OXA-232-cases, n=27) was matched by isolation site, species, and date, with 2 cases of infection by carbapenem-susceptible/third-generation cephalosporin-susceptible (TGCS-controls, n=54) and 2 cases by carbapenem-susceptible/ESBL producing Enterobacteriaceae (ESBL-controls, n=54); 66% were urinary tract and 18.5% intra-abdominal infections. In the multivariable analysis with ESBL-controls, previous use ß-lactam/ß-lactamase antibiotics (OR 6.2; 95% CI 1.6-23.8) and, third-generation cephalosporins (OR 0.2; 95% CI 0.05-0.8) were associated with OXA-232 infection; with TGSC-controls previous use of ß-lactam/ß-lactamase antibiotics (OR 3.7; 95% 1.1-12.0) was associated. Among the OXA-232-cases, 29% received imipenem/cilastatin or meropenem, 11.1% ceftriaxone, 22.2% a carbapenem-based combination and 33.3% other antimicrobials as treatment. Previous ß-lactam/ß-lactamase antibiotics are associated with OXA-232 infections, and some may be treated with other active carbapenems or, in the absence of ESBL, third-generation cephalosporins.

IS200 and multilocus sequence typing for the identification of Salmonella enterica serovar Typhi strains from Indonesia.

In this work, IS200 and multi-locus sequence typing (MLST) were used to analyze 19 strains previously serotyped as Salmonella enterica serovar Typhi and isolated in Indonesia (16 strains), Mexico (2 strains), and Switzerland (1 strain). Most of the strains showed the most common Typhi sequence types, ST1 and ST2, and a new Typhi genotype (ST1856) was described. However, one isolate from Mexico and another from Indonesia were of the ST365 and ST426 sequence types, indicating that they belonged to serovars Weltevreden and Aberdeen, respectively. These results were supported by the amplification of IS200 fragments, which rapidly distinguish Typhi from other serovars. Our results demonstrate the utility of IS200 and MLST in the classification of Salmonella strains into serovars. These methods provide information on the clonal relatedness of strains isolated worldwide.

Trends of Mycobacterium bovis Isolation and First-Line Anti-tuberculosis Drug Susceptibility Profile: A Fifteen-Year Laboratory-Based Surveillance.

BACKGROUND: Mycobacterium tuberculosis causes the majority of tuberculosis (TB) cases in humans; however, in developing countries, human TB caused by M. bovis may be frequent but undetected. Human TB caused by M. bovis is considered a zoonosis; transmission is mainly through consumption of unpasteurized dairy products, and it is less frequently attributed to animal-to-human or human-to-human contact. We describe the trends of M. bovis isolation from human samples and first-line drug susceptibility during a 15-year period in a referral laboratory located in a tertiary care hospital in Mexico City. METHODOLOGY/PRINCIPAL FINDINGS: Data on mycobacterial isolates from human clinical samples were retrieved from the laboratory's database for the 2000-2014 period. Susceptibility to first-line drugs: rifampin, isoniazid, streptomycin (STR) and ethambutol was determined. We identified 1,165 isolates, 73.7% were M. tuberculosis and 26.2%, M. bovis. Among pulmonary samples, 16.6% were M. bovis. The proportion of M. bovis isolates significantly increased from 7.8% in 2000 to 28.4% in 2014 (X(2)trend, p<0.001). Primary STR resistance was higher among M. bovis compared with M. tuberculosis isolates (10.9% vs.3.4%, p<0.001). Secondary multidrug resistance (MDR) rates were 38.5% and 34.4% for M. bovis and M. tuberculosis, respectively (p = 0.637). A rising trend of primary STR monoresistance was observed for both species (3.4% in 2000-2004 vs. 7.6% in 2010-2014; p = 0.02). CONCLUSIONS/SIGNIFICANCE: There is a high prevalence and a rising trend of M. bovis isolates in our region. The proportion of pulmonary M. bovis isolates is higher than in previous reports. Additionally, we report high rates of primary anti-tuberculosis resistance and secondary MDR in both M. tuberculosis and M. bovis. This is one of the largest reports on drug susceptibility of M. bovis from human samples and shows a significant proportion of first-line anti-tuberculosis drug resistance.