ABSTRACT Novel β-lactam/β-lactamase inhibitors (βL/βLIs) are important therapies for carbapenem-resistant Pseudomonas aeruginosa (CRPA). However, the global extent of resistance to these agents and the impact of resistance on patient outcomes are unclear. We therefore evaluated patients with CRPA isolates at 35 hospitals (nine countries) from December 2018 to November 2019. Antimicrobial susceptibility testing was performed at a central laboratory by agar dilution for ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) and by broth microdilution for imipenem-relebactam (I/R). Characteristics and outcomes, including desirability of outcome rankings (DOOR), were compared between patients infected with isolates not susceptible vs susceptible to each agent. Of 800 CRPA isolates, susceptibility to C/T, CZA, and I/R was 69%, 67%, and 33%, respectively. USA isolates ( n = 526) were more frequently susceptible to these agents than isolates from other countries ( n = 274; C/T: 83% vs 42%; CZA: 77% vs 47%; I/R: 37% vs 23%; P < 0.001 for each comparison) and isolates with carbapenemases ( n = 157) were less frequently susceptible than isolates without carbapenemases ( n = 643; C/T: 7% vs 84%; CZA: 24% vs 77%; I/R: 6% vs 39%; P < 0.001 for each comparison). Thirty-day mortality and DOOR were similar overall in patients infected with isolates not susceptible vs susceptible to each βL/βLI. However, the adjusted probability of a better DOOR outcome for a randomly selected patient with bacteremia due to a C/T-not susceptible vs -susceptible isolate was 38.2% (95% confidence interval, 25.6%–52.7%). Resistance to novel βL/βLIs, especially I/R, is common in CRPA, particularly outside the USA and in carbapenemase-producing isolates. Additional treatment options are needed for CRPA infections.

Background:Bloodstream infections (BSI) caused by metallo-beta-lactamase (MBL)-producing Enterobacterales (E) are associated with high mortality. However, in most Latin American countries there is a lack of clinical and microbiological data on BSI caused by MBL-E. Methods:This preplanned subgroup analysis of the multicenter, observational, prospective EMBARCAR study focused on adult patients with BSI caused by MBL-E in Argentina. Logistic regression adjusted by propensity scores (PS) for the treatment with ceftazidime-avibactam plus aztreonam (CAZ/AVI plus ATM) were used to identify variables associated with mortality. Results:A total of 140 patients with BSI caused by MBL-producing Enterobacterales were included. Median age was 59 years (IQR 46-70), and most patients were male (61%). Most frequent comorbidities were diabetes 23%, class III obesity 19%, and chronic renal failure 19%. Two thirds of patients were hospitalized in critical care units, 60% required mechanical ventilation and 38% presented with shock. Most frequent isolated microorganisms were Klebsiella pneumoniae (75%) and Serratia marcescens (12%). Most patients (64%) received combination therapy and 23% received CAZ/AVI plus ATM. Thirty-day mortality was 41%. In the multivariate PS adjusted analysis, INCREMENT-CPE score ≥8 was associated with increased risk of mortality (odds ratio [OR] 3.63; 95% CI: 1.13, 11.7), while CAZ/AVI plus ATM therapy with a lower risk of death (OR 0.18; 95% CI: .05, .58). Conclusions:In summary, BSI due to MBL-producing Enterobacterales resulted in a high mortality rate in our country. The use of CAZ/AVI plus ATM was associated with a decreased mortality. Better access to these antibiotics should be granted.

BACKGROUND:Bloodstream infections (BSIs) caused by carbapenem-resistant gram-negative bacilli (CR-GNB) are difficult-to-treat infections associated with high mortality. Outcomes of BSI due to CR-GNB may vary in different countries. METHODS:Prospective observational, multicenter study, including consecutive hospitalized index patients aged ≥18 years, with a positive blood culture for CR-GNB, between July 2020 and March 2022 in Argentina. Among patients with Klebsiella pneumoniae BSIs, logistic regressions adjusted by propensity score (PS) were used to identify variables associated with 30-day mortality. RESULTS:Overall, 466 patients with CR-GNB BSIs were included. The mean age was 56.7 (SD ±16) years and most patients (75%) were in critical care units. The median INCREMENT-CPE mortality score was 10 (IQR, 6-12). Most common micro-organisms were K pneumoniae (53%) and Acinetobacter baumannii (25%). Among Enterobacterales, resistance mechanisms included K pneumoniae carbapenemase (KPC) in 50%, metallo-beta-lactamase carbapenemase (MBL) in 48%, OXA carbapenemase in 6%, and a combination of carbapenemases in 5% of patients. Overall, 30-day mortality was 52%. Among patients with BSI due to K pneumoniae, the PS-adjusted multivariate analysis showed that an INCREMENT-CPE score ≥8 points (odds ratio [OR], 3.48; 95% CI, 1.53, 7.93) was associated with increased 30-day mortality. In contrast, the use of regimens including ceftazidime-avibactam alone or in combination with aztreonam was associated with decreased 30-day mortality (OR, .20; 95% CI, .09, .47). CONCLUSIONS:BSIs due to CR-GNB are associated with high mortality rates in Argentina. Among patients with CR-K pneumoniae bacteremia the use of ceftazidime-avibactam alone or in combination with aztreonam was associated with a reduction in mortality.

ABSTRACT Contezolid is a novel oxazolidinone antibiotic with a promising safety profile. Oral contezolid and its intravenous (IV) prodrug contezolid acefosamil (CZA) are in development for treatment of diabetic foot and acute bacterial skin and skin structure infections (ABSSSI). The prodrug CZA is converted to active contezolid via intermediate MRX-1352. This study aimed to provide the pharmacokinetic rationale for safe, effective, and flexible dosage regimens with initial IV CZA followed by oral contezolid. We simultaneously modeled plasma concentrations from 110 healthy volunteers and 74 phase 2 patients with ABSSSI via population pharmacokinetics (using the importance sampling estimation algorithm), and optimized dosage regimens by Monte Carlo simulations. This included data on MRX-1352, contezolid, and its metabolite MRX-1320 from 66 healthy volunteers receiving intravenous CZA (150–2400 mg) for up to 28 days, and 74 patients receiving oral contezolid [800 mg every 12 h (q12h)] for 10 days. The apparent total clearance for 800 mg oral contezolid with food was 16.0 L/h (23.4% coefficient of variation) in healthy volunteers and 17.7 L/h (53.8%) in patients. CZA was rapidly converted to MRX-1352, which subsequently transformed to contezolid. The proposed dosage regimen used an IV CZA 2000 mg loading dose with 1000 mg IV CZA q12h as maintenance dose(s), followed by 800 mg oral contezolid q12h (with food). During each 24-h period, Monte Carlo simulations predicted this regimen to achieve consistent areas under the curve of 91.9 mg·h/L (range: 76.3–106 mg·h/L) under all scenarios. Thus, this regimen was predicted to reliably achieve efficacious contezolid exposures independent of timing of switch from IV CZA to oral contezolid. IMPORTANCE This study provides the population pharmacokinetic rationale for the dosage regimen of the intravenous (IV) prodrug contezolid acefosamil (CZA) followed by oral contezolid. We developed the first integrated population model for the pharmacokinetics of the MRX-1352 intermediate prodrug, active contezolid, and its main metabolite MRX-1320 based on data from three clinical studies in healthy volunteers and phase 2 patients. The proposed regimen was predicted to reliably achieve efficacious contezolid exposures independent of timing of switch from IV CZA to oral contezolid.

Background Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. Methods In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. Results Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. Conclusions CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

Asymptomatic infections with SARS-CoV-2 are associated with viral transmission and have a key role in the propagation of the pandemic. Understanding viral shedding during asymptomatic infections is critical. Unfortunately, data on asymptomatic SARS-CoV-2 infection in children is extremely limited. To determine the presence of viral viable shedding, we prospectively followed two healthy children of a family where both parents developed mild COVID-19 (April 2021). SARS-CoV-2 detection was made by RT-PCR and virus isolation by cell culture from saliva samples. Positive samples were sequenced to identify variants of SARS-CoV-2. Serum samples were evaluated to determine the presence of antibodies using a single enzyme-linked immunosorbent assay (ELISA, COVIDAR IgG). Both children were SARS-CoV-2 positive and asymptomatic. In addition, the virus grew in cell culture from saliva samples. Furthermore, one child showed viable SARS-CoV-2 for at least 17 days after the onset symptoms from his father. The recommended isolation period for asymptomatic contacts during the acquisition of data had been established for 10 days; however, this child remained with viable virus beyond that period. The positive samples from both children were consistent with B.1.1.28.1 lineage (Gamma). In both asymptomatic children, anti-Spike IgG was detected. Asymptomatic children may represent a source of infection that should not be underestimated during this pandemic.

INTRODUCTION:Clinical features and outcomes of SARSCoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina.METHODS:Multicenter and prospective registry of patients =18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared.RESULTS:A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized patients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hospitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hospitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively.CONCLUSION:Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 during the second wave in Argentina were more seriously ill and had a higher mortality.

BACKGROUND Ceftobiprole is a cephalosporin that may be effective for treating complicated Staphylococcus aureus bacteremia, including methicillin-resistant S. aureus. METHODS In this phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated S. aureus bacteremia were randomly assigned in a 1:1 ratio to receive ceftobiprole at a dose of 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome, overall treatment success 70 days after randomization (defined as survival, bacteremia clearance, symptom improvement, no new S. aureus bacteremia-related complications, and no receipt of other potentially effective antibiotics), with a noninferiority margin of 15%, was adjudicated by a data review committee whose members were unaware of the trialgroup assignments. Safety was also assessed. RESULTS Of 390 patients who underwent randomization, 387 (189 in the ceftobiprole group and 198 in the daptomycin group) had confirmed S. aureus bacteremia and received ceftobiprole or daptomycin (modified intention-to-treat population). A total of 132 of 189 patients (69.8%) in the ceftobiprole group and 136 of 198 patients (68.7%) in the daptomycin group had overall treatment success (adjusted difference, 2.0 percentage points; 95% confidence interval [CI], -7.1 to 11.1). Findings appeared to be consistent between the ceftobiprole and daptomycin groups in key subgroups and with respect to secondary outcomes, including mortality (9.0% and 9.1%, respectively; 95% CI, - 6.2 to 5.2) and the percentage of patients with microbiologic eradication (82.0% and 77.3%; 95% CI, -2.9 to 13.0). Adverse events were reported in 121 of 191 patients (63.4%) who received ceftobiprole and 117 of 198 patients (59.1%) who received daptomycin; serious adverse events were reported in 36 patients (18.8%) and 45 patients (22.7%), respectively. Gastrointestinal adverse events (primarily mild nausea) were more frequent with ceftobiprole. CONCLUSIONS Ceftobiprole was noninferior to daptomycin with respect to overall treatment success in patients with complicated S. aureus bacteremia. (Funded by Basilea Pharmaceutica International and the U.S. Department of Health and Human Services; ERADICATE ClinicalTrials.gov number, NCT03138733.)

BACKGROUND:Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. METHODS:We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. FINDINGS:We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION:The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING:National Institutes of Health.

Health care workers (HCWs) are at high risk for SARS-CoV-2. In addition, pre-symptomatic or asymptomatic transmission accounts for around half of the cases. Saliva testing is an option to detect SARS-CoV-2 infection. To determine the performance of saliva samples for screening, HCWs were tested for SARS-CoV-2 by RT-PCR. Those with a positive result in saliva were tested by nasopharyngeal swabbing for viral RNA detection and blood collection to search for the presence of specific antibodies. In September-October 2020, 100 HCWs were enrolled and followed up. Six subjects (6%) tested positive in saliva. Of them, 5/6 were positive in a subsequent nasopharyngeal swab and 4/6 developed signs and symptoms compatible with COVID-19. Among the latter, 3 seroconverted while asymptomatic HCWs remained seronegative. Saliva screening was helpful for identifying SARS-CoV-2 infection in HCWs. This screening permitted rapid personnel isolation avoiding further transmission of the virus in the hospital setting.

Central nervous system (CNS) toxoplasmosis is a well-known opportunistic infection in patients with AIDS. Spinal cord involvement and brain hemorrhage are very infrequent manifestations of CNS toxoplasmosis. In this report, we describe a patient with unknown AIDS presenting with bilateral headaches and new onset of bilateral leg weakness, diagnosed with CNS toxoplasmosis with a CSF polymerase chain reaction (PCR) for T. gondii, associated with spinal cord involvement (a central lesion in the conus medullaris) and multiple brain lesions with hemorrhage. The patient required therapy with pyrimethamine, sulfadiazine, and dexamethasone, with favorable outcomes after 30 days of therapy. Our case re-emphasizes the diagnosis of CNS toxoplasmosis in patients with advance HIV disease and spinal cord involvement. A high index of suspicion is needed, especially in HIV/AIDS patients not receiving HAART, who are seropositive for T. gondii, have a CD4+ count less than 100 cells/mm3, and present with symptoms consistent with spinal disease and even more with suggestive coincident brain lesions.

BACKGROUND:Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries. METHODS:In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov, NCT03646227, and is complete. FINDINGS:Between June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2-6] vs 2 [0-4] vs 2 [0-4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2-5] vs 1 [0-3] vs 1 [0-2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42-65) for China versus South America, 50% (41-61) for the USA versus China, and 53% (41-66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8-16; 29 of 246) than in the USA (23%, 16-30; 30 of 130) and South America (28%, 20-37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22-10·50) and the USA (aOR 3·34, 1·50-7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70-2·96). INTERPRETATION:Global CRKP epidemics have important regional differences in patients' baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions. FUNDING:The National Institutes of Health.

BACKGROUND:Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina.METHODS:Multicenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU).RESULTS:A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27).CONCLUSIONS:This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.

CASE PRESENTATION: A 31-year-old man was admitted to our hospital with a recent history of generalized seizures. Three months earlier, he started with intermittent hemoptysis. CT scan showed a cavitary lung lesion in the upper segment of the right inferior lobe (RIL). Because of his job as a social worker in a high-risk population, he started treatment for Mycobacterium TB; however, the BAL culture result was negative. At the time of his current admission, he has continued taking rifampicin, isoniazid, pyrazinamide, and levofloxacin. He denied the use of any illicit drugs or alcohol. He had no history of smoking. One year earlier, he visited Southeast Asia, Oceania, and South Africa for several months. He reported a weight loss of 7 kg since then. Except for a recurrent oral candidiasis, he did not have a relevant medical history. His family history was notable for mother with lupus, and brother with sarcoidosis.

Current diagnostic standards involve severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in nasopharyngeal swabs (NPS), but saliva is an attractive and noninvasive option for diagnosis. The objectives were to determine the performance of saliva in comparison with NPS for detecting SARS-CoV-2 and to compare the optimized home brew reverse-transcription polymerase chain reaction (RT-PCR) with a commercial RT-PCR. Paired NPS and saliva specimens were prospectively collected and tested by RT-PCR from patients presenting at an emergency room with signs and symptoms compatible with coronavirus disease-2019. A total of 348 samples from 174 patients were tested by RT-PCR assays. Among 174 patients with symptoms, 63 (36%) were SARS-CoV-2 positive in NPS using the optimized home-brew PCR. Of these 63 patients, 61 (98%) were also positive in saliva. An additional positive SARS-CoV-2 saliva was detected in a patient with pneumonia. Kappa Cohen's coefficient agreement between NPS and saliva was 0.96 (95% confidence interval [CI], 0.90-0.99). Median Ct values in NPS versus saliva were 18.88 (interquartile range [IQR], 15.60-23.58; range, 11.97-38.10) versus 26.10 (IQR, 22.75-30.06; range, 13.78-39.22), respectively (p < .0001). The optimized home-brew RT-PCR demonstrated higher analytical and clinical sensitivity compared with the commercial RT-PCR assay. A high sensitivity (98%) and agreement (kappa 0.96) in saliva samples compared to NPS was demonstrated when using an optimized home-brew PCR even when the viral load in saliva was lower than in NPS. This noninvasive sample is easy to collect, requires less consumable and avoids discomfort to patients. Importantly, self-collection of saliva can diminish exposure to healthcare personnel.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) producing COVID-19 disease and Dengue are both epidemic in Argentina. To date, most cases of both virus are from Buenos Aires city. Here we describe the clinical characteristics and follow up from a cohort patients coinfected with dengue and SARS-CoV-2 in Buenos Aires. METHODS: We retrospectively identified patients from different Buenos Aires area hospitals who were admitted with confirmed infection with Dengue Virus and SARS-CoV-2. Clinical data were obtained through review of medical records. Patients had at least 3 weeks follow-up. RESULTS: Thirteen patients were identified. The median age was 37 years old, most of them didn't had any comorbidity, almost half were females, and all had febrile disease at presentation The median duration of fever was 7 days. Headache was a common symptom among coinfected subjects. A total of eight patients had respiratory symptoms. Five patients had pneumonia. Three patients had rash that appear early in the course of the disease. Two of these patients had concomitant pneumonia and rash. Almost all patients had Lymphopenia at presentation and thrombocytopenia in almost half of them. No patients required ICU or died during the follow up. CONCLUSION: SARS-CoV2 and Dengue can produce coinfections in patients living in areas where both virus are epidemic. The outcome of these patients does not seem to be worse than having either SARS-Cov2 or Dengue alone.FUNDING STATEMENT: The authors stated that this article doesn´t have funding sources. DECLARATION OF INTERESTS: MES is a consultant to Basilea and the principal investigator for Argentina NIH grant UM1AI104681; all others have no interests to declareETHICS APPROVAL STATEMENT: This study was approved by the Ethic Committee of Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina.

Introduction Acute bacterial skin and skin structure infections (ABSSSI) are among the most frequent infectious diseases. Recently, several new antibiotics with activity against MRSA have been approved. Tedizolid, a second-generation oxazolidinone approved for ABSSSI offers theoretical advantages over first-generation oxazolidinones.Areas covered A comprehensive online search of Medline, ClinicalTrials.gov, and conference presentations was made, selecting articles between January 2000 and April 2020. In this review, the authors discuss the chemical and microbiological properties of tedizolid, summarize its efficacy, safety, and potential role in the treatment of ABSSSI as well as the potential for future indications.Expert opinion Tedizolid has proven to be non-inferior compared to linezolid for the treatment of ABSSSI in two registrational phase III clinical trials, being well tolerated. Tedizolid exhibits antibacterial activity against the most important ABSSSI pathogens (including multidrug-resistant strains of MRSA), as well as mycobacteria and Nocardia. It appears to have a safe profile, including decreased myelotoxicity and no significant drug interactions. Preliminary studies with longer duration of therapy seem to confirm these potential benefits. Overall, tedizolid expands the newly acquired armamentarium to treat ABSSSI. The role of tedizolid for other indications is under investigation and has yet to be determined.

An epidemic of dengue virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infections occurred in Argentina during 2020. We describe the clinical characteristics and outcomes in a cohort of patients hospitalized because of co-infection. We retrospectively identified 13 patients from different hospitals in Buenos Aires who had confirmed infection with SARS-CoV-2 and dengue virus and obtained clinical and laboratory data from clinical records. All patients had febrile disease when hospitalized. Headache was a common symptom. A total of 8 patients had respiratory symptoms, 5 had pneumonia, and 3 had rash. Nearly all patients had lymphopenia when hospitalized. No patients were admitted to an intensive care unit or died during follow up. Co-infection with SARS-CoV-2 and dengue virus can occur in patients living in areas in which both viruses are epidemic. The outcome of these patients did not seem to be worse than those having either SARS-CoV-2 or dengue infection alone.

Upon completion, participant will be able to describe process of validating a screening tool

The broth microdilution (BMD) MIC testing method for telavancin was recently revised BMD (rBMD) to improve accuracy and reproducibility. Staphylococcus aureus isolates from telavancin phase 3 complicated skin and skin-structure infection (cSSSI) studies were tested using the rBMD method. Retesting of 1132 isolates produced MICs ranging from ≤0.015 to 0.12μg/mL that were 8-fold lower than the original method. All isolates tested remained susceptible to telavancin at the revised susceptibility breakpoint of 0.12μg/mL. The clinical cure and microbiological eradication rates were 90% (368/409) and 89% (366/409) for telavancin-treated patients, and were similar for patients with methicillin-susceptible and -resistant S. aureus isolates and S. aureus isolates with elevated vancomycin MICs (≥1μg/mL). The data presented here are aimed to update the literature and better inform clinicians and clinical microbiologists about the revised telavancin MICs, as well as the corresponding clinical and microbiological cure rates for cSSSI patients.