Activity of Tedizolid and Comparator Agents Against Gram-positive Isolates Causing Skin and Skin Structure Infections in Pediatric Patients in United States Hospitals (2015-2019).

BACKGROUND: Tedizolid was approved by the United States Food and Drug Administration to treat acute bacterial skin and skin structure infections in adults in 2014, and in 2020, United States Food and Drug Administration expanded the approval of tedizolid to treat pediatric patients 12 years of age and older. This study assessed the activity of tedizolid and comparator agents against clinical surveillance isolates collected from pediatric patients with skin and skin structure infection in the United States. METHODS: A total of 2747 gram-positive organisms (1 per patient) were collected in 2015 to 2019 from pediatric (≤17 years old) patients with skin and skin structure infections. The isolates were collected from 33 US medical centers and susceptibility tested against tedizolid and comparators by reference broth microdilution methods. Susceptibility results for main pathogens were stratified by patient age: ≤1 years old (851 isolates), 2 to 5 years old (623), 6 to 12 years old (754) and 13 to 17 years old (519). RESULTS: Staphylococcus aureus (n = 2163) was the main pathogen recovered from all age groups, followed by ß-hemolytic streptococci (n = 460). Tedizolid inhibited all S. aureus , including methicillin-resistant S. aureus (MRSA) isolates (41.0%), regardless of the age group. MRSA rates varied by age group; MRSA was highest among ≤1 years old (45.0%) and lowest in the 13 to 17 years old (32.7%) groups. Linezolid, daptomycin and vancomycin also displayed susceptibility rates of 100% against S. aureus isolates. Clindamycin (81.3%-98.5%), tetracycline (91.6%-97.1%) and trimethoprim-sulfamethoxazole (97.0%-100%) susceptibility rates varied among age groups and methicillin resistance profiles. Overall, tedizolid, linezolid, daptomycin and vancomycin inhibited all gram-positive pathogens in this collection. CONCLUSIONS: Tedizolid was very active against a large collection of gram-positive pathogens causing skin and skin structure infection in pediatric patients, including MRSA isolates.

Direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry and real-time PCR in a combined protocol for diagnosis of bloodstream infections: a turnaround time approach.

Bloodstream infections (BSIs) are serious infections associated with high rates of morbidity and mortality. Every hour delay in initiation of an effective antibiotic increases mortality due to sepsis by 7%. Turnaround time (TAT) for conventional blood cultures takes 48h, forcing physicians to streamline therapy by exposing patients to broad-spectrum antimicrobials. Our objective was (1) to evaluate the accuracy and TAT of an optimized workflow combining direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and in-house real-time polymerase chain reaction (PCR) for bacterial identification and antimicrobial resistance profiling directly from positive blood bottles for diagnosing bloodstream infections and (2) to verify the effect of reporting results to medical staff. A total of 103 BSI episodes from 91 patients admitted to three hospitals in São Paulo, Brazil were included. TAT from molecular versus conventional methods was measured and compared. Our protocol showed an overall agreement of 93.5% for genus and 78.5% for species identification; 74.2% for methicillin resistance detection, 89.2% for extended-spectrum ß-lactamase profiling, 77.8% for metallo-ß-lactamase profiling, and 100% for carbapenemase profile and vancomycin-resistance detection when compared with conventional testing. TAT of molecular sample processing according to our protocol was 38h shorter than conventional methods. Antimicrobial interventions were possible in 27 BSI episodes. Antimicrobial discontinuation was achieved in 12 BSI episodes while escalation of therapy occurred in 15 episodes. Antimicrobial therapy was inadequate in three (12%) BSI episodes diagnosed using results of molecular testing. Our in-house rapid protocol for identifying both bacteria and antimicrobial resistance provided rapid and accurate results, having good agreement with conventional testing results. These results could contribute to faster antimicrobial therapy interventions in BSI episodes.

Direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry and real-time PCR in a combined protocol for diagnosis of bloodstream infections: a turnaround time approach

ABSTRACT Bloodstream infections (BSIs) are serious infections associated with high rates of morbidity and mortality. Every hour delay in initiation of an effective antibiotic increases mortality due to sepsis by 7%. Turnaround time (TAT) for conventional blood cultures takes 48 h, forcing physicians to streamline therapy by exposing patients to broad-spectrum antimicrobials. Our objective was (1) to evaluate the accuracy and TAT of an optimized workflow combining direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and in-house real-time polymerase chain reaction (PCR) for bacterial identification and antimicrobial resistance profiling directly from positive blood bottles for diagnosing bloodstream infections and (2) to verify the effect of reporting results to medical staff. A total of 103 BSI episodes from 91 patients admitted to three hospitals in São Paulo, Brazil were included. TAT from molecular versus conventional methods was measured and compared. Our protocol showed an overall agreement of 93.5% for genus and 78.5% for species identification; 74.2% for methicillin resistance detection, 89.2% for extended-spectrum β-lactamase profiling, 77.8% for metallo-β-lactamase profiling, and 100% for carbapenemase profile and vancomycin-resistance detection when compared with conventional testing. TAT of molecular sample processing according to our protocol was 38 h shorter than conventional methods. Antimicrobial interventions were possible in 27 BSI episodes. Antimicrobial discontinuation was achieved in 12 BSI episodes while escalation of therapy occurred in 15 episodes. Antimicrobial therapy was inadequate in three (12%) BSI episodes diagnosed using results of molecular testing. Our in-house rapid protocol for identifying both bacteria and antimicrobial resistance provided rapid and accurate results, having good agreement with conventional testing results. These results could contribute to faster antimicrobial therapy interventions in BSI episodes.

Nocardial scleritis: A case report and a suggested algorithm for disease management based on a literature review.

PURPOSE: To report a case of nocardial scleritis and to propose a logical treatment algorithm based on a literature review. OBSERVATIONS: It is important to suspect a nocardial infection when evaluating anterior unilateral scleritis accompanied by multiple purulent or necrotic abscesses, especially in male patients with a history of chronic ocular pain and redness, trauma inflicted by organic materials, or recent ophthalmic surgery. A microbiological investigation is essential. In positive cases, a direct smear reveals weakly acid-fast organisms or Gram-positive, thin, beading and branching filaments. Also, the organism (usually) grows on blood agar and Lowenstein-Jensen plates. An infection can generally be fully resolved by debridement of necrotic areas and application of topical amikacin drops accompanied by systemic sulfamethoxazole-trimethoprim. CONCLUSIONS AND SIGNIFICANCE: Together with the case report described, we review data on a total of 43 eyes with nocardial scleritis. Our proposed algorithm may afford a useful understanding of this sight-threatening disease, facilitating easier and faster diagnosis and management.

High mortality rate associated with KPC-producing Enterobacter cloacae in a Brazilian hospital.

We describe a clonal dissemination of KPC-producing Enterobacter cloacae in a Brazilian hospital. Patients diagnosed with theses isolates showed high mortality rate (41.8%) and were associated with previous use of antibiotics and urinary catheterization. Therefore, infection control measures and use of stricter antibiotic policies are required to control the spread of these organisms.

Dissemination of Multidrug-Resistant Proteus mirabilis Clones Carrying a Novel Integron-Borne blaIMP-1 in a Tertiary Hospital.

This study aimed to characterize multidrug-resistant Proteus mirabilis clones carrying a novel class 1 integron-borne blaIMP-1 In1359 was inserted into a large conjugative plasmid that also carried blaCTX-M-2 The production of carbapenemases in Enterobacteriaceae that are intrinsically resistant to polymyxins and tigecycline is very worrisome, representing a serious challenge to clinicians and infection control teams.

Detection of OXA-370 directly from rectal swabs and blood culture vials using an immunochromatographic assay.

We evaluated the performance of OXA-48 K-SeT assay for detecting OXA-370 directly from spiked rectal swabs and blood culture vials. The limit of detection of this test was 104UFC/mL for rectal swabs. Detection of the OXA-370-producing isolates was successfully achieved directly from positive blood culture vials independent of growing conditions.

Influence of Culture Media on Detection of Carbapenem Hydrolysis by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

In this study, we evaluated the influence of distinct bacterial growth media on detection of carbapenemase hydrolysis by matrix-assisted laser desorption ionization-time of flight mass spectrometry. False-negative results were observed for OXA-25-, OXA-26-, and OXA-72-producing Acinetobacter baumannii isolates grown on MacConkey agar medium. The other culture media showed 100% sensitivity and 100% specificity for detecting carbapenemase.

Risk factors for KPC-producing Klebsiella pneumoniae: watch out for surgery.

This study describes the molecular characteristics and risk factors associated with carbapenem-resistant Klebsiella pneumoniae strains. Risk factors associated with KPC-producing K. pneumoniae strains were investigated in this case-control study from May 2011 to May 2013. Bacterial identification was performed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined by broth microdilution. Carbapenemase production was assessed by both modified Hodge test (MHT) and ertapenem hydrolysis using MALDI-TOF MS. The presence of ß-lactamase-encoding genes was evaluated by PCR and DNA sequencing. Alterations in genes encoding K. pneumoniae outer membrane proteins were analysed by PCR and DNA sequencing as well as SDS-PAGE. Genetic relatedness among strains was determined by pulsed-field gel electrophoresis. This study included 94 patients. Longer hospitalisation, mechanical ventilation, catheters, and previous surgery were associated with KPC-producing K. pneumoniae. Sixty-eight strains showed resistance to carbapenems. Carbapenemase production was detected by MHT in 67 K. pneumoniae strains and by MALDI-TOF MS in 57. The presence of the blaKPC-2 gene was identified in 57 strains. The blaKPC-2 gene was not found in 11 carbapenem-resistant K. pneumoniae; instead, the blaCTX-M-1-like, blaCTX-M-2-like, blaCTX-M-8 like, blaCTX-M-14-like and blaSHV- like genes associated with OmpK35 and OmpK36 alterations were observed. Thirty-three KPC-producing K. pneumoniae strains were clonally related, and patients infected with these strains had a higher mortality rate (78.78 %). Our results show that KPC-producing K. pneumoniae was associated with several healthcare-related risk factors, including recent surgery.

Co-transmission of Rahnella aquatilis between hospitalized patients.

Rahnella aquatilis is an environmental Gram-negative bacillus that is rarely reported as human pathogen, being mainly associated with infections in immunocompromised patients. Herein we describe two cases of R. aquatilis isolates recovered from endotracheal aspirate cultures of different patients in a tertiary hospital located in the city of São Paulo, Brazil. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rDNA gene sequencing were performed to confirm bacterial identification after the isolates being erroneously identified as Pantoea spp. by automated system. Both isolates showed the same PFGE pattern and presented the ß-lactamase encoding gene blaRAHN-1, responsible for resistance to cephalothin. The isolates were susceptible to broad-spectrum cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and polymyxin B. This report shows the presence and transmission of uncommon bacteria in the nosocomial environment and alerts us about the need for new tools of correct microbiologic diagnosis.

Coproduction of KPC-2 and IMP-10 in Carbapenem-Resistant Serratia marcescens Isolates from an Outbreak in a Brazilian Teaching Hospital.

We describe an outbreak caused by KPC-2- and IMP-10-producing Serratia marcescens isolates in a Brazilian teaching hospital. Tigecycline was the only active antimicrobial agent tested. The blaIMP-10 gene was located in a new class 1 integron, named In990, carried by a nonconjugative plasmid, in contrast to blaKPC-2.

Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in the intensive care unit: a real challenge to physicians, scientific community, and society.

The prevalence of multidrug-resistant pathogens, especially in intensive care units, has increased and represents a great concern for medical and scientific community. Infections caused by these pathogens are associated with increased costs, length of hospitalization, and morbidity/mortality rates. The last decade was marked by the spread of carbapenem resistance determinants especially in Enterobacteriaceae isolates. In this review, the Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae is used as an example to discuss the difficulties in dealing with multidrug-resistant pathogens in the intensive care unit setting and how they represent a challenge to the medical-scientific community and, ultimately, the whole society.

Avaliação das metodologias M.I.C.E.®, Etest® e microdiluição em caldo para determinação da CIM em isolados clínicos / Evaluation of M.I.C.E.TM, Etest® and CLSI broth microdilution methods for antimicrobial susceptibility testing of nosocomial bacterial isolates

INTRODUÇÃO: As fitas Oxoid® M.I.C.Evaluator® (M.I.C.E., Thermo Fisher Scientific, Basingstoke, UK), recém-lançadas no mercado brasileiro, representam uma alternativa rápida para a realização de testes de sensibilidade a antimicrobianos (TSA). OBJETIVO: Avaliar o desempenho da metodologia M.I.C.E. em relação à microdiluição em caldo (teste de referência) e ao Etest® (BioMérieux, Marcy l'Étoile, France). Material e métodos: Foram selecionados 160 isolados bacterianos, sendo P. aeruginosa (20), Acinetobacter spp. (20), K. pneumoniae (20), E. coli (20), S. aureus (20), Staphylococcus coagulase-negativa (20), E. faecalis (20) e E. faecium (20). Os TSAs foram realizados por microdiluição em caldo, Etest e M.I.C.E., seguindo-se as recomendações do Clinical Laboratory Standards Institute (CLSI, 2009) e dos respectivos fabricantes. Os resultados foram interpretados segundo os critérios estabelecidos pelo CLSI e comparados por análise de regressão. RESULTADOS: Avaliando-se todas as combinações de antimicrobianos vs. a espécie bacteriana, o desempenho da metodologia M.I.C.E. foi muito bom, apresentando uma concordância geral (variação na concentração inibitória mínima [CIM] ± 1-log2) > 90 por cento, exceto para cefotaxima (85 por cento) e vancomicina (76,3 por cento), quando em comparação com os resultados da metodologia de referência. Quando comparado com o Etest, a metodologia M.I.C.E. apresentou concordância geral > 96 por cento, com exceção para a combinação amoxicilina/ácido clavulânico (67,5 por cento). CONCLUSÃO: Os resultados do TSA obtidos pela metodologia M.I.C.E. apresentaram boa correlação com aqueles obtidos pela microdiluição em caldo e pelo Etest, indicando que essa metodologia é uma alternativa rápida para a determinação da CIM pelos laboratórios de microbiologia clínica. Atenção especial deve ser dada á determinação da CIM para a combinação amoxicilina/ácido clavulânico.

INTRODUCTION: The Oxoid® M.I.C.EvaluatorTM methodology (M.I.C.E., Thermo Fisher Scientific, Basingstoke, UK), recently released into the market, represents a rapid alternative to antimicrobial susceptibility testing. OBJECTIVE: The objective of this study was to evaluate the performance of M.I.C.E. methodology in relation to broth microdilution (reference test) and Etest® (BioMérieux, Marcy l'Étoile, France). Material and method: A total of 160 bacterial isolates were collected comprising the following species: P. aeruginosa (20), Acinetobacter spp. (20), K. pneumoniae (20), E. coli (20), S. aureus (20), coagulase-negative Staphylococcus (20), E. faecalis (20) and E. faecium (20). Following Clinical Laboratory Standands Institute (CLSI) standards (2009) and the manufacturers' recommendations, antimicrobial susceptibility testing was performed using broth microdilution method, Etest and M.I.C.E. The results were interpreted according to the criteria established by CLSI and compared through regression analysis. RESULTS: All antimicrobial combinations vs. bacterial species were evaluated and M.I.C.E. methodology yielded good results with general correlation (MIC variation ± 1-log2) > 90 percent, except for cefotaxime (85 percent) and vancomycin (76.3 percent) when compared with the reference method. The M.I.C.E. results compared to Etest showed general correlation (> 96 percent), except for amoxicillin/clavulanic acid (67.5 percent) combination. CONCLUSION: AST results obtained from M.I.C.E. methodology showed a good correlation with those from broth microdilution and Etest, which corroborates its time effectiveness in the determination of MIC. However, the combination of amoxicillin/clavulanic acid requires further attention.