RESUMO
One of the measures for monitoring microbial resistance is the calculation of the defined daily dose of antimicrobial agents. For this calculation, the weight of an adult of 70 kg is used as a standard, so that application in neonatology is not possible. The aim of this study is to describe the use profile and calculate the defined daily dose (DDD) of antimicrobials in a neonatal intensive care unit (NICU) of a public hospital in the interior of Bahia, Brazil. From March 2020 to December 2021, the medical records of 712 newborns admitted to a NICU between September 2018 and June 2020 were analyzed. A total of 410 newborns diagnosed with neonatal sepsis were included. The most used antimicrobials per patient were gentamicin (408/410; 99.5%), ampicillin (407; 99.3%), amikacin (29; 7.1%) and oxacillin (21; 5.1%), with a mean (SD) treatment duration of 9.8 (3.9) days. The most commonly used combination of antimicrobials was ampicillin with gentamicin, which was used in 406 patients (99.0%). The values for neonatal DDDs were on average 26 times lower than those for adult DDDs. The neonatal DDDs were similar to those observed in other studies. Ampicilin and cefepime were the antimicrobials for which the greatest differences were observed in neonatal DDDs compared with adult DDDs, which differed mainly between maintenance doses, reflecting the lack of international standards in neonatology. Standardization of DDDs as a surveillance measure has the potential to clarify the pattern of antimicrobial use in neonatal patients worldwide and, in particular, to prevent indiscriminate use and bacterial resistance.
Assuntos
Antibacterianos , Unidades de Terapia Intensiva Neonatal , Neonatologia , Humanos , Recém-Nascido , Neonatologia/métodos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Feminino , Masculino , Brasil , Gentamicinas/administração & dosagem , Gentamicinas/uso terapêutico , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/microbiologia , Ampicilina/administração & dosagem , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Amicacina/administração & dosagem , Amicacina/uso terapêutico , Estudos RetrospectivosRESUMO
Candida albicans invasive candidiasis is considered a global health problem. In such cases, biofilm formation on implanted devices represents a therapeutic challenge and the presence of metabolically inactive persistent cells (PCs) in these communities increases their tolerance to fungicidal drugs. This study investigated the influence of amoxicillin, AMX; cefepime, CEF; gentamicin, GEN; amikacin, AMK; vancomycin, VAN; and ciprofloxacin, CIP; on the production of PCs in biofilms of C. albicans bloodstream isolates. 48 h-mature biofilms (n = 6) grown in RPMI-1640 supplemented with antibiotics were treated with 100 µg ml-1 amphotericin B and then evaluated for PCs. Biofilms grown in the presence of antibiotics produced more PCs, up to 10×, when exposed to AMX and CIP; 5 × to CEF; and 6 × to GEN and VAN. The results indicate that antibiotics can modulate PC production in C. albicans biofilms. This scenario may have clinical repercussions in immunocompromised patients under broad-spectrum antibiotic therapy.
Biofilms are microbial communities tolerant to antifungals. Our research showed that antibiotics stimulate the formation of persistent cells within Candida albicans biofilms. These are dormant, metabolically silent cells that resist to therapy and can be related to metastatic and recalcitrant infections.
Assuntos
Antibacterianos , Biofilmes , Candida albicans , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Antibacterianos/farmacologia , Humanos , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana , Ciprofloxacina/farmacologia , Gentamicinas/farmacologia , Amoxicilina/farmacologia , Vancomicina/farmacologia , Amicacina/farmacologia , Cefepima/farmacologia , Anfotericina B/farmacologia , Cefalosporinas/farmacologia , Candidíase/microbiologia , Candidíase/tratamento farmacológicoRESUMO
INTRODUCTION: Mycetoma is a chronic granulomatous inflammatory disease of the subcutaneous tissue, which affects deep structures and bone. Most cases of actinomycetoma are caused by members of the genus Nocardia. CASE PRESENTATION: Here we report the case of a 43-year-old male who presented a disseminated mycetoma on the forearm, chest and neck, characterized by enlarged and erythematous lesions through which seropurulent material drains, and numerous atrophic scars. Molecular identification was performed by 16S gene amplification and sequencing. Nocardia mexicana was identified with 100% identity. Trimethoprim-sulfamethoxazole, diaminodiphenyl sulfone and amikacin was a successful treatment after 6 months. CONCLUSIONS: Nocardia mexicana is a rare organism that causes mycetoma. We report a case of extensive mycetoma on the forearm with spread to the neck and thorax associated with manipulation of the mouth of a calf.
Assuntos
Antibacterianos , Antebraço , Micetoma , Pescoço , Nocardiose , Nocardia , RNA Ribossômico 16S , Tórax , Humanos , Masculino , Adulto , Nocardia/isolamento & purificação , Nocardia/genética , Micetoma/microbiologia , Micetoma/tratamento farmacológico , Micetoma/diagnóstico , Nocardiose/microbiologia , Nocardiose/tratamento farmacológico , Nocardiose/diagnóstico , Antebraço/microbiologia , Antebraço/patologia , Tórax/diagnóstico por imagem , Tórax/microbiologia , Pescoço/patologia , Antibacterianos/uso terapêutico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Amicacina/uso terapêutico , DNA Ribossômico/genética , DNA Ribossômico/químicaRESUMO
The natural antimicrobial properties of essential oils (EOs) have contributed to the battle against multidrug-resistant microorganisms by providing new ways to develop more effective antibiotic agents. In this study, we investigated the chemical composition of Ocotea diospyrifolia essential oil (OdOE) and its antimicrobial properties combined with amikacin (AMK). Through gas chromatography-mass spectrometry (GCMS) analysis, the primary constituents of OdOE were identified as α-bisabolol (45.8 %), ß-bisabolene (9.4 %), γ-elemene (7.6 %), (Z)- ß-farnesene (5.2 %), spathulenol (3.5 %), (Z)-caryophyllene (3.3 %), and (E)-caryophyllene (3.1 %). In vitro assessments showed that the combined administration of OdOE and AMK exerted a synergistic antibacterial effect on the multidrug-resistant K. pneumoniae strain. This synergistic effect demonstrated bacteriostatic action. OdEO combined with amikacin showed protein extravasation within 2 h of treatment, leading to bacterial death, which was determined by a reduction in viable cell count. The effective concentrations showed hemocompatibility. In vivo assessments using Caenorhabditis elegans as a model showed the survival of 85 % of infected nematodes. Therefore, the combination OdEO combined with amikacin exhibited antimicrobial activity against a multidrug-resistant K. pneumoniae strain. Thus, OdOE is a promising agent that may be considered for development of antimicrobial treatment.
Assuntos
Amicacina , Antibacterianos , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Óleos Voláteis , Amicacina/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Animais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Antibacterianos/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Caenorhabditis elegans/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química , Sesquiterpenos/farmacologiaRESUMO
Alginate is a major extra polymeric substance in the biofilm formed by mucoid Pseudomonas aeruginosa. It is the main proven perpetrator of lung infections in patients suffering from cystic fibrosis. Alginate lyases are very important in the treatment of cystic fibrosis. This study evaluated the role of standalone and in conjugation, effect of alginate lyase of SG4 + isolated from Paenibacillus lautus in enhancing in vitro bactericidal activity of gentamicin and amikacin on mucoid P. aeruginosa. Using Response Surface Methodology (RSM) alginate lyase SG4 + production was optimized in shake flask and there 8.49-fold enhancement in enzyme production. In fermenter, maximum growth (10.15 mg/ml) and alginate lyase (1.46 International Units) production, 1.71-fold was increased using Central Composite Design (CCD). Further, fermentation time was reduced from 48 to 20 h. To the best of our knowledge this is the first report in which CCD was used for fermenter studies to optimize alginate lyase production. The Km and Vmax of purified enzyme were found to be 2.7 mg/ml and 0.84 mol/ml-min, respectively. The half-life (t 1/2) of purified alginate lyase SG4 + at 37 °C was 180 min. Alginate lyase SG4 + in combination with gentamicin and amikacin eradiated 48.4- 52.3% and 58- 64.6%, alginate biofilm formed by P. aeruginosa strains, respectively. The study proves that alginate lyase SG4 + has excellent exopolysaccharide disintegrating ability and may be useful in development of potent therapeutic agent to treat P. aeruginosa biofilms.
Assuntos
Antibacterianos , Biofilmes , Paenibacillus , Polissacarídeo-Liases , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Polissacarídeo-Liases/metabolismo , Polissacarídeo-Liases/genética , Antibacterianos/farmacologia , Paenibacillus/genética , Paenibacillus/enzimologia , Paenibacillus/efeitos dos fármacos , Gentamicinas/farmacologia , Amicacina/farmacologia , Fermentação , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Alginatos/metabolismoRESUMO
ABSTRACT The objective of this case report was to share the successful management of severe endophthalmitis, aiming at ocular integrity and visual acuity. A 73-year-old man presented with visual acuity of 20/30 in the right eye and 20/200 in the left eye. On the 21st day postoperatively after phacoemulsification in the left eye, he developed symptoms of endophthalmitis, including ocular discomfort, blurred vision, and whitish discharge. Despite negative cultures, his condition worsened, resulting in corneal perforation on the 31st day. Conjunctival flap and penetrating keratoplasty were performed. Currently, the patient maintains a visual acuity of 20/40 in the left eye, with a healthy graft and no signs of failure. Despite the complications, careful follow-up and timely interventions successfully preserved his vision. The use of conjunctival flap during the inflammatory phase was crucial to maintaining ocular integrity. This underscores the importance of different approaches in complex ocular complications, including alternative strategies for ocular protection during active inflammation.
RESUMO O objetivo deste relato de caso foi compartilhar o manejo bem-sucedido de uma grave endoftalmite, visando à integridade ocular e à acuidade visual. Um homem de 73 anos apresentou acuidade visual de 20/30 no olho direito e 20/200 no olho esquerdo. No 21° dia pós-operatório de facoemulsificação em olho esquerdo, ele desenvolveu sintomas de endoftalmite, incluindo desconforto ocular, visão embaçada e secreção esbranquiçada. Apesar de culturas negativas, sua condição piorou, resultando em perfuração corneal no 31° dia. A cobertura conjuntival e a ceratoplastia penetrante foram realizadas. Atualmente, o paciente mantém acuidade visual de 20/40 no olho esquerdo, com enxerto saudável e sem sinais de falha. Apesar das complicações, o acompanhamento cuidadoso e as intervenções oportunas preservaram a visão com sucesso. O uso de cobertura conjuntival durante a fase inflamatória foi crucial para manter a integridade ocular. Isso destaca a importância de diferentes abordagens em complicações oculares complexas, incluindo estratégias alternativas para proteção ocular durante a inflamação ativa.
Assuntos
Humanos , Masculino , Idoso , Úlcera da Córnea/cirurgia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/etiologia , Endoftalmite/cirurgia , Endoftalmite/diagnóstico , Endoftalmite/etiologia , Ceratoplastia Penetrante/métodos , Facoemulsificação/efeitos adversos , Complicações Pós-Operatórias , Dexametasona/administração & dosagem , Amicacina/administração & dosagem , Vancomicina/administração & dosagem , Acuidade Visual , Úlcera da Córnea/tratamento farmacológico , Endoftalmite/tratamento farmacológico , Microscopia com Lâmpada de Fenda , Moxifloxacina/administração & dosagemRESUMO
BACKGROUND: The most common source of pyogenic liver abscess is biliary tract infection. Other less common routes include the spread of bacteria from distant foci. However, direct extension of a perinephric infection focus to the liver is extremely rare. CASE REPORT: The patient was a non-diabetic, immunocompetent, 29-year-old woman of mixed race ancestry with a history of recurrent urinary tract infections who was referred to our hospital because of an ultrasound-detected liver abscess. She was initially treated with metronidazole for 20 days at the referring institution for suspected amebic abscess without improvement. On admission to our center, she was febrile and complained of a dull right upper quadrant pain. A POCUS ultrasound suggested a pyogenic abscess, probably from a staghorn calculus infection. She received meroperem and amikacin for 22 and 10 days, respectively. Repeat hemocultures showed no growth, but urine cultures were positive for Proteus sp. Complete remission of clinical and imaging findings was observed under antibiotics. The patient was referred to the urology outpatient clinic to discuss the option of radical nephrectomy. CONCLUSION : This case underlines the high morbidity of staghorn calculi.
Assuntos
Abscesso Hepático , Cálculos Coraliformes , Feminino , Humanos , Adulto , Cálculos Coraliformes/complicações , Cálculos Coraliformes/diagnóstico por imagem , Cálculos Coraliformes/tratamento farmacológico , Abscesso Hepático/tratamento farmacológico , Ultrassonografia , Antibacterianos/uso terapêutico , AmicacinaRESUMO
The high incidence of multidrug-resistant (MDR) Acinetobacter baumannii has been a challenge for health worldwide, due to the reduction of therapeutic options, making the use of antimicrobial combinations necessary for the treatment, such as meropenem, amikacin, and colistin. Antibodies against bacterial species, mainly immunoglobulins G (IgG), are produced for acting as effector mechanisms (neutralization, opsonization, phagocytosis, and complement system activation). Some studies have demonstrated promising results of IgG in combination with antimicrobial preparations against bacterial infections, in which the direct action of IgG has restored the immune system balance. Serious problem caused by the increase of MDR A. baumannii isolates results in a constant search for therapeutic alternatives to defeat these infections. However, this study aims to verify in vitro the phagocytosis rate of the A. baumannii-infected human monocytes, as well as to analyze possible morphological changes induced by intravenous immunoglobulin G (IVIG) with human serum in association with antimicrobials. The phagocytosis rate and bacterial cell binding capacity of IVIG were determined for two A. baumannii isolates submitted to 4 mg/mL of human IVIG alone and in combination with different sub-minimum inhibitory concentrations (sub-MICs) of meropenem, amikacin, and colistin and processed for indirect immunofluorescence. Subsequently, these isolates were resubmitted and coupled with human serum and processed for scanning electron microscopy. There was no statistical difference for phagocytosis rates in the isolates tested. Bacterial isolates showed alterations in cell morphology when exposed to IVIG/human serum alone and in combination with antimicrobials such as alteration in shape, wrinkling, membrane depression, and especially cell rupture with extravasation of cytoplasmic material. The isolates visually differed in the IVIG binding to the bacterial cell, with higher fluorescence intensity, which corresponds to the highest IVIG binding, in the isolate more sensitive to meropenem, amikacin, and colistin. No differences between treatments were observed in the IVIG binding to the bacterial cell. The combined action of IVIG with meropenem, amikacin, and colistin against A. baumannii MDR isolates induced several bacterial cell damages. And when associated with human serum, a massive destruction of cells can be observed. These results may suggest the analysis of the use of IgG preparations for the treatment of A. baumannii MDR infections.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Anti-Infecciosos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Imunoglobulinas Intravenosas/farmacologia , Imunoglobulinas Intravenosas/uso terapêutico , Meropeném/farmacologia , Meropeném/uso terapêutico , Colistina/farmacologia , Amicacina/farmacologia , Amicacina/uso terapêutico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla , Sinergismo FarmacológicoRESUMO
A female patient in her 30s presented to the emergency department with a 10-day history of fever, weakness and diaphoresis. Subsequent investigations revealed a diagnosis of haemophagocytic syndrome, secondary to disseminated non-tuberculous mycobacterial infection affecting the bone marrow, lungs, lymph nodes and skin. The bone marrow culture confirmed the presence of Mycobacterium avium infection. The patient's haemophagocytic syndrome was managed using the HLH-2004 chemoimmunotherapy, and M. avium infection was treated with a combination of clarithromycin, ethambutol, rifampicin, ciprofloxacin and amikacin. Throughout her hospitalisation, the patient faced several serious complications arising from both the medications and the prolonged hospital stay (lasting 12 months). However, these complications were promptly identified and effectively managed through a multidisciplinary and comprehensive approach. This approach was crucial in achieving a favourable patient outcome and successful recovery.
Assuntos
Linfo-Histiocitose Hemofagocítica , Infecções por Mycobacterium não Tuberculosas , Infecções Oportunistas , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Amicacina , CiprofloxacinaRESUMO
AIMS: We investigated the chemical composition and the in vitro and in vivo antibacterial effects of Protium heptaphyllum essential oil (PHEO) alone and in combination with antibiotics against polymyxin-resistant Klebsiella pneumoniae isolates. METHODS AND RESULTS: Hydrodistillation was used to obtain PHEO, and gas chromatography coupled with mass spectrometry revealed α-pinene, δ-3-carene, and ß-pinene as major components present in PHEO. Minimum inhibitory concentration was determined using the broth microdilution technique and ranged from 256 to 512 µg ml-1. The checkerboard method showed synergy with the combination of PHEO and amikacin (AMK) against the polymyxin-resistant K. pneumoniae isolates. In 8 of the 10 isolates tested, the fractional inhibitory concentration indexes (FICIs) ranged from 0.06 to 0.5, while in the remaining two isolates, the combination exerted an additive effect (FICI of 0.6 and 1.0), resulting in AMK dose reduce of range 2- to 16-fold, in the presence of PHEO. Analysis using zero interaction potency revealed high synergy score (63.9). In the in vivo assay, the survival of Caenorhabditis elegans was significantly improved in the presence of PHEO (1 µg ml-1) + AMK (µg ml-1) combination as compared to 32 µg ml-1 AMK alone. Furthermore, PHEO concentrations of 256 and 512 µg ml-1 were found to be non-toxic on the experimental model. CONCLUSION: To our knowledge, this is the first report of such type of synergism demonstrating an antimicrobial effect against polymyxin-resistant K. pneumoniae isolates.
Assuntos
Amicacina , Óleos Voláteis , Animais , Amicacina/farmacologia , Polimixinas/farmacologia , Klebsiella pneumoniae , Antibacterianos/farmacologia , Caenorhabditis elegans , Óleos Voláteis/farmacologia , HidrogênioRESUMO
Characterizing microorganisms according to different criteria is useful when investigating sources of microbiological contamination in the pharmaceutical industry. The aim of this study was to characterize 38 Acinetobacter baumannii complex strains isolated from a biopharmaceutical industry by 16S rRNA sequencing, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS), multilocus sequence typing (MLST), antimicrobial susceptibility profile, biofilm formation, and sensibility to disinfectants. Thirty-three (86.9%) strains were identified by 16S rRNA gene sequencing as A. seifertii/pitti/nosocomialis/lactucae, four (10.5%) as A. baumannii, and one (2.6%) as A. vivianii/courvalini. MALDI-TOF/MS did not identify one strain, and incorrectly identified 30/37 (81.1%) strains as A. baumannii. Strains were assigned to 12 different STs, of which nine were newly defined in this study (STs 2091-2099). Twenty-six (68.4%) strains showed resistance to amikacin and gentamicin. Thirty-three (86.8%) strains were classified as moderately or strongly adherent on polystyrene. Alcohol 70%/15 min and quaternary ammonium 0.08%/20 min were not able to eliminate the biofilm formed, but sodium hypochlorite 0.1%/15 min was efficient. In conclusion, improved methods are needed to improve the identification of Acinetobacter strains in pharmaceutical industries. This organism is of particular concern as it forms recalcitrant biofilms, leading to persistence in the manufacturing environment and increased risk of product contamination.
Assuntos
Acinetobacter baumannii , Tipagem de Sequências Multilocus , RNA Ribossômico 16S/genética , Acinetobacter baumannii/genética , Amicacina , Preparações FarmacêuticasRESUMO
OBJECTIVES: Ceftazidime-avibactam (CAZ-AVI) combines ceftazidime and a reversible ß-lactamase inhibitor that has shown activity against multidrug-resistant (MDR) Enterobacterales and P. aeruginosa. Using data from the Antimicrobial Testing Leadership and Surveillance program (ATLAS), this study examined the in vitro antimicrobial activity of CAZ-AVI and other antibiotics against Gram-negative bacteria collected from Chilean hospitals between 2015 and 2021. METHODS: Clinical isolates of Enterobacterales and P. aeruginosa were collected from three medical centres in Chile. Blood, abdominal fluid, urine, soft tissues, and respiratory tract samples were obtained from infected patients. Minimum inhibitory concentrations using the broth microdilution method were determined for susceptibility testing, and the Clinical and Laboratory Standards Institute (CLSI) breakpoints were used for interpreting the results. Extended-spectrum ß-lactamases (ESBL) and carbapenemase genes were also detected through polymerase chain reaction. RESULTS: A total of 2600 Enterobacterales and 836 P. aeruginosa were analysed. CAZ-AVI was the antibiotic with the highest in vitro activity against Enterobacterales (99.72%). The incidence of carbapenem-resistant Enterobacterales (CRE) was 1.5% (n = 39), and the antibiotics with the best in vitro activity were tigecycline (92.31%), CAZ-AVI (88.57%), and amikacin (79.49%). CAZ-AVI was the antibiotic with the best activity against ESBL-producing Enterobacterales (99.34%) and MDR Enterobacterales (99.31%). For KPC-producing Enterobacterales, susceptibility to amikacin was 100%, whereas susceptibility to CAZ-AVI was 91.67%. Regarding MDR and difficult-to-treat resistance P. aeruginosa, 44.83% and 38.99% were susceptible to CAZ-AVI, respectively. CONCLUSION: CAZ-AVI shows excellent in vitro activity against Enterobacterales in general, CRE, ESBL-producing Enterobacterales, and KPC-producing Enterobacterales. CAZ-AVI is also an option against MDR P. aeruginosa.
Assuntos
Amicacina , Ceftazidima , Humanos , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Chile , Amicacina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos , Pseudomonas aeruginosaRESUMO
Carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa are being isolated from patient specimens with increasing frequency in Latin America and worldwide. The current study provides an initial description of the in vitro activity of imipenem/relebactam (IMR) against non-Morganellaceae Enterobacterales (NME) and P. aeruginosa infecting hospitalized patients in Latin America. From 2018 to 2020, 37 clinical laboratories in nine Latin American countries participated in the SMART global surveillance program and contributed 15,466 NME and 3408 P aeruginosa isolates. MICs for IMR and seven comparators were determined using CLSI broth microdilution and interpreted by CLSI M100 (2022) breakpoints. ß-lactamase genes were identified in selected isolate subsets. IMR (96.9% susceptible), amikacin (95.9%), meropenem (90.7%), and imipenem (88.7%) were the most active agents against NME. Among piperacillin/tazobactam-nonsusceptible NME (n = 4124), 90.4% of isolates were IMR-susceptible (range by country, 97.2 [Chile] to 67.0% [Guatemala]) and among meropenem-nonsusceptible NME isolates (n = 1433), 74.0% were IMR-susceptible (94.1% [Puerto Rico] to 5.1% [Guatemala]). Overall, 6.3% of all collected NME isolates carried a KPC (metallo-ß-lactamase [MBL]-negative), 1.8% an MBL, 0.4% an OXA-48-like carbapenemase (MBL-negative), and 0.1% a GES carbapenemase (MBL-negative). Amikacin (85.2% susceptible) and IMR (80.1%) were the most active agents against P. aeruginosa; only 56.5% of isolates were imipenem-susceptible. Relebactam increased susceptibility to imipenem by 22.0% (from 23.9% to 45.9%) in piperacillin/tazobactam-nonsusceptible isolates (n = 1031) and by 35.5% (from 5.5% to 41.0%) in meropenem-nonsusceptible isolates (n = 1128). Overall, 7.6% of all collected P. aeruginosa isolates were MBL-positive and 0.7% carried a GES carbapenemase. In conclusion, in 2018â2020, almost all NME (97%) and most P. aeruginosa (80%) isolates from Latin America were IMR-susceptible. Continued surveillance of the in vitro activities of IMR and comparator agents against Gram-negative pathogens, and monitoring for ß-lactamase changes (in particular for increases in MBLs), is warranted.
Assuntos
Amicacina , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/genética , América Latina , Amicacina/farmacologia , Meropeném/farmacologia , Antibacterianos/farmacologia , Imipenem/farmacologia , beta-Lactamases/genética , Piperacilina , Tazobactam , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVES: To assess the global and regional distribution of ESBLs in Enterobacterales and carbapenemases in Enterobacterales and Pseudomonas aeruginosa. METHODS: Antimicrobial susceptibility of isolates collected from ATLAS (2017-2019) was determined per CLSI guidelines. Enterobacterales exhibiting meropenem MICs ≥2 mg/L and/or ceftazidime/avibactam and/or aztreonam/avibactam MICs ≥16 mg/L, Escherichia coli and Klebsiella pneumoniae with aztreonam and/or ceftazidime MICs ≥2 mg/L, and P. aeruginosa with meropenem MICs ≥4 mg/L were screened for ß-lactamases by PCR and sequencing. RESULTS: Globally, ESBL-positive E. coli (23.7%, 4750/20047) and K. pneumoniae (35.1%, 6055/17229) carried predominantly the CTX-M-15 variant (E. coli: 53.9%; K. pneumoniae: 80.0%) with highest incidence in Africa/Middle East (AfME). Among carbapenem-resistant (CR) E. coli (1.1%, 217/20047) and Enterobacter cloacae (3.8%, 259/6866), NDMs were predominant (E. coli in AfME: 62.5%; E. cloacae in Asia Pacific: 59.7%). CR K. pneumoniae (13.3%, 2299/17 229) and P. aeruginosa (20.3%, 4187/20 643) carried predominantly KPC (30.9%) and VIM (14.7%), respectively, with highest frequency in Latin America. Among ESBL-positive Enterobacterales, susceptibility to ceftazidime/avibactam (>90.0%) and amikacin (>85.0%) was higher than to piperacillin/tazobactam (>45.0%) and ciprofloxacin (>7.4%). In CR Enterobacterales, susceptibility to amikacin (>54.0%) and ceftazidime/avibactam (>31.0%) was higher than to ciprofloxacin (>2.7%) and piperacillin/tazobactam (>0.5%). CR P. aeruginosa similarly demonstrated higher susceptibility to amikacin (63.4%) and ceftazidime/avibactam (61.9%) than to ciprofloxacin (26.2%) and piperacillin/tazobactam (25.3%). CONCLUSIONS: Varied distribution of resistance genotypes across regions among ESBL-positive Enterobacterales and CR Enterobacterales and P. aeruginosa provide crucial insights on major resistance mechanisms and trends observed in recent years. Continued surveillance is warranted for monitoring global dissemination and resistance.
Assuntos
Ceftazidima , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Amicacina , Aztreonam , Meropeném/farmacologia , Escherichia coli/genética , Incidência , Compostos Azabicíclicos , beta-Lactamases/genética , Combinação Piperacilina e Tazobactam , Klebsiella pneumoniae , Combinação de Medicamentos , Ciprofloxacina , Testes de Sensibilidade MicrobianaRESUMO
PURPOSE: The aim of this work was to integrate the Therapeutic Drug Monitoring (TDM) with the model-informed precision dosing (MIPD) approach, using Physiologically-based Pharmacokinetic/Pharmacodynamic (PBPK/PD) modelling and simulation, to explore the relationship between amikacin exposure and estimated glomerular filtration rate (GFR) in critically ill patients with cancer. METHODS: In the TDM study, samples from 51 critically-ill patients with cancer treated with amikacin were analysed. Patients were stratified according to renal function based on GFR status. A full-body PBPK model with 12 organs model was developed using Simcyp V. 21, including steady-state volume of distribution of 0.21 L/kg and renal clearance of 6.9 L/h in healthy adults. PK parameters evaluated were within the 2-fold error range. RESULTS: During the validation step, predicted vs observed amikacin clearance values after single infusion dose in patients with normal renal function, mild and moderate renal impairment were 7.6 vs 8.1 L/h (7.5 mg/kg dose); 3.8 vs 4.5 L/h (1500 mg dose) and 2.2 vs 3.1 L/h (25 mg/kg dose), respectively. However, predicted vs observed amikacin clearance after a single dose infusion of 1400 mg in critically-ill patients with cancer were 1.46 vs 1.63 (P = 0.6406) L/h (severe), 2.83 vs 1.08 (P < 0.05) L/h (moderate), 4.23 vs 2.49 (P = 0.0625) L/h (mild) and 7.41 vs 3.36 (P < 0.05) L/h (normal renal function). CONCLUSION: This study demonstrated that estimated GFR did not predict amikacin elimination in critically-ill patients with cancer. Further studies are necessary to find amikacin PK covariates to optimize the pharmacotherapy in this population. Therefore, TDM of amikacin is imperative in cancer patients.
Assuntos
Amicacina , Neoplasias , Adulto , Humanos , Amicacina/uso terapêutico , Estado Terminal/terapia , Taxa de Filtração Glomerular , Monitoramento de Medicamentos , Neoplasias/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
Humans frequently contract urinary tract infections (UTIs), which can be brought on by uropathogens (UPs) that are multi-drug resistant. Treatment for UTIs brought on by pathogenic UPs that produce extended-spectrum lactamases (ESBLs) is more costly and potentially fatal. As a result, the objective of this study was to use culture, biochemical, and 16S rRNA sequencing to identify and characterize UPs isolated from outpatients in Noakhali, Bangladesh, who had symptoms of UTIs. ESBL gene identification and quinolone resistance gene typing were then performed on the isolates using polymerase chain reaction (PCR). Throughout the trial's 8-month duration, 152 (76%) of 200 urine samples were positive for the presence of UPs. The overall number of UPs recovered was 210, with 39 individuals having multiple UPs present in their samples. Among all of the isolates, Escherichia coli (45.24%, 95/210; 95% confidence interval (CI): 35.15-57.60%), Enterobacter spp. (24.76%, 52/210; CI: 19.15-35.77%), Klebsiella spp. (20.95%; 44/210; CI: 15.15-30.20%), and Providencia spp. (9.05%; 19/210; CI: 4.95-19.25%) were the four most prevalent bacteria found in the isolates. The UPs displayed a very high level of resistance to piperacillin 96.92% (126/130), ampicillin 90% (117/130), nalidixic acid 77.69% (101/130), cefazolin 70% (91/130), amoxicillin 50% (55/130), cefazolin 42.31% (55/130), nitrofurantoin 43.08% (56/130), and ciprofloxacin 33.08% (43/130), whereas resistance to netilmicin (3.85%), amikacin (4.62%), and imipenem (9.23%) was low. Individually, every species of E. coli and Providencia spp. showed greater ampicillin, amikacin, cefazolin, cefazolin, and nalidixic acid resistance than the others. The bivariate results indicate several antibiotic pairings, and isolates had meaningful associations. All MDR isolates were subjected to PCR, which revealed that blaCTX-M-15 genes predominated among the isolates, followed by the blaTEM class (37%). Isolates also had the qnrS, aac-6´-Ib-cr, and gyrA genes. The findings provide worrying indications of a major expansion of MDR isolates in the study locations, particularly the epidemiological balCTX-M 15, with the potential for the transmission of multi-drug-resistant UP strains in the population.
Assuntos
Infecções por Escherichia coli , Quinolonas , Infecções Urinárias , Humanos , Escherichia coli , Antibacterianos/farmacologia , Infecções por Escherichia coli/microbiologia , Quinolonas/farmacologia , Cefazolina , Amicacina , Ácido Nalidíxico , Bangladesh/epidemiologia , RNA Ribossômico 16S/genética , Farmacorresistência Bacteriana Múltipla/genética , beta-Lactamases/genética , Farmacorresistência Bacteriana , Infecções Urinárias/microbiologia , Ampicilina , Testes de Sensibilidade MicrobianaRESUMO
AIMS: This study aimed to characterize the population pharmacokinetic parameters of intravenously administered amikacin in newborns and assess the effect of sepsis in amikacin exposure. METHODS: Newborns aged ≥3 days who received at least 1 dose of amikacin during their hospitalization period were eligible for the study. Amikacin was administered intravenously during a 60-min infusion period. Three venous blood samples were taken from each patient during the first 48 h. Population pharmacokinetic parameter estimates were obtained using a population approach with the programme NONMEM. RESULTS: Data from 329 drug assay samples were obtained from 116 newborn patients (postmenstrual age [PMA] 38.3, range 32-42.4 weeks; weight 2.8, range 1.6-3.8 kg). Measured amikacin concentrations ranged from 0.8 to 56.4 mg/L. A 2-compartment model with linear elimination produced a good fit of the data. Estimated parameters for a typical subject (2.8 kg, 38.3 weeks) were clearance (Cl = 0.16 L/h), intercompartmental clearance (Q = 0.15 L/h), volume of distribution of the central compartment (Vc = 0.98 L) and peripheral volume of distribution (Vp = 1.23 L). Total bodyweight, PMA and the presence of sepsis positively influenced Cl. Plasma creatinine concentration and circulatory instability (shock) negatively influenced Cl. CONCLUSION: Our main results confirm previous findings showing that weight, PMA and renal function are relevant factors influencing newborn amikacin pharmacokinetics. In addition, current results showed that pathophysiological states of critically ill neonates, such as sepsis and shock, were associated with opposite effects in amikacin clearance and should be considered in dose adjustments.
Assuntos
Sepse Neonatal , Sepse , Humanos , Recém-Nascido , Amicacina/farmacocinética , Antibacterianos , Sepse Neonatal/tratamento farmacológico , Sepse/tratamento farmacológico , Taxa de Depuração MetabólicaRESUMO
BACKGROUND: Multidrug-resistant bacteria are one of the world's biggest health problems; therefore, improving the spectrum of action of antibiotics could be necessary to reverse this situation. Amikacin and silver salts have well-known antimicrobial properties. However, both drugs lost their effectiveness against some bacteria, such as Acinetobacter baumannii. This work aims to develop a nanodrug from silver nanoparticles (AgNPs) functionalized with Amikacin against multidrug-resistant Acinetobacter baumannii. METHODS: AgNPs were produced using the bottom-up methodology and functionalized with Amikacin modified by the carbodiimide-based chemistry, forming AgNPs@Amikacin. Susceptibility tests were performed using Amikacin-resistant Acinetobacter baumannii strains to assess the bacteriostatic and bactericidal potential of the developed nanodrug. The clinical strains were induced to form a biofilm, and biomass quantification and the metabolic activity were determined. RESULTS: The AgNPs have a hydrodynamic diameter of the particles with a bimodal distribution, with a size of 37.84 nm. The FT-IR spectrum of AgNPs@Amikacin exhibits vibrational modes corresponding to Amikacin, confirming the conjugation to AgNPs. Susceptibility testing demonstrated a minimal inhibitory and bactericidal concentration of < 0.5 µg/mL. The AgNPs@Amikacin reduced the biofilm metabolic activity of Acinetobacter baumannii at rates ≥ 50%, characterized by the minimal biofilm inhibition concentrations. CONCLUSIONS: Results demonstrate a promising development of a new nanodrug with lower concentrations, less toxicity, and greater efficacy against multidrug-resistant Acinetobacter baumannii.
Assuntos
Acinetobacter baumannii , Nanopartículas Metálicas , Humanos , Amicacina/farmacologia , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade MicrobianaRESUMO
A patient with acute myeloid leukemia presented various episodes of febrile neutropenia, for which there was no positive response to antibiotic treatments. Following an episode of bacteremia by extensively drug-resistant Klebsiella pneumoniae, amikacin was prescribed, pharmacokinetic analyses of its plasma concentrations were performed and the dosage interval was narrowed to 12 and 8 h in order to counteract the reduced postantibiotic effect due to the patient being immunocompromised. The patient responded positively, with procalcitonin decreasing and body temperature normalizing. Recovery was finally achieved, without renal or auditory damage. This case proposes tightening dosage intervals for aminoglycosides as an effective strategy in immunocompromised patients. Aminoglycosides are given over extended intervals (24 h), considering concentration-dependent effectiveness, nephrotoxicity and postantibiotic effect. Leukocytes appear to play a determining role in the postantibiotic effect, with no proposed dosing strategy for strongly immunocompromised patients.