RESUMO
Background: Multidrug-resistant Gram-negative bacteria (MDR-GNB) are becoming increasingly common around the world, with carbapenems frequently serving as a last resort but being threatened by the growing incidence of carbapenemase-producing bacteria. Ceftazidime-avibactam (CAZ/AVI) is a potential agent against MDR-GNB but with limited clinical experience, particularly in critically ill immunosuppressed children. Methods: This study analyzed the use of CAZ/AVI as salvage treatment in severely infected immunosuppressed children from September 2019 to July 2022. Patients with confirmed GNB infection who received CAZ/AVI were matched with patients who received other antibiotics. Results: Twenty-five critically ill immunosuppressed children treated with CAZ/AVI were included. The majority had hematologic diseases. All patients presented with sepsis in all 30 courses. Septic shock presented in 36.7% of these courses. The primary sites of infection included bloodstream infection (20.0%), skin and skin structure infection (20.0%), intra-abdominal infection (13.3%) and hospital-acquired pneumonia (10.0%). Twelve of the 25 (48.0%) patients had positive microbiological cultures, mainly Pseudomonas aeruginosa and Klebsiella pneumoniae, including 5 carbapenem-resistant GNB-infected cases. Fifteen (50.0%) courses presented clinical improvement. For the initial course of each patient, the clinical response rate of the GNB recovered group was significantly higher than that of the group without GNB recovery (66.7% vs 23.1%, P = 0.047). The 14-day and 30-day mortality rates were 24.0% and 28.0%, respectively, which were significantly correlated with the absence of GNB recovery (P = 0.004 and 0.024, respectively) and hospital-acquired pneumonia as the primary site of infection (P = 0.001 and 0.006, respectively). There was no significant difference in major outcomes between patients who received CAZ/AVI and matched patients who received other antibiotics. Conclusion: CAZ/AVI could be considered a salvage strategy for immunosuppressed children with confirmed GNB infection. Caution should be taken when CAZ/AVI is applied to these patients in the absence of GNB recovery.
Assuntos
Antibacterianos , Compostos Azabicíclicos , Ceftazidima , Combinação de Medicamentos , Terapia de Salvação , Humanos , Ceftazidima/administração & dosagem , Ceftazidima/uso terapêutico , Criança , Masculino , Feminino , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Compostos Azabicíclicos/administração & dosagem , Compostos Azabicíclicos/uso terapêutico , Pré-Escolar , Hospedeiro Imunocomprometido , Adolescente , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Estudos Retrospectivos , Lactente , Testes de Sensibilidade MicrobianaRESUMO
RATIONALE: Shewanella algae are Gram-negative bacteria that are widely found in aquatic habitats and rarely cause lung infections in inland areas. PATIENT CONCERNS: Cough with light-yellow phlegm for 2 weeks. DIAGNOSES: The final diagnosis was bacterial pneumonia. INTERVENTIONS: The patient was treated with ceftazidime (2 g, every 12 h) for 1 week. OUTCOMES: The patient's lung infection improved and he was discharged. LESSONS: This case highlights a rare occurrence of lung infection caused by Shewanella algae in elderly Tibetan men residing in non-marine environments.
Assuntos
Antibacterianos , Infecções por Bactérias Gram-Negativas , Pneumonia Bacteriana , Shewanella , Humanos , Masculino , Shewanella/isolamento & purificação , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/complicações , Antibacterianos/uso terapêutico , Tibet , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , IdosoRESUMO
Serratia marcescens, as a Gram-negative opportunistic pathogen, is a rare cause of peritonitis and has worse clinical outcomes than Gram-positive peritonitis. In this case report, we describe a case of Serratia marcescens associated peritonitis that was successfully cured without catheter removal. A 40-year-old male patient with peritoneal dialysis who worked in the catering industry was admitted to the hospital for 16 hours after the discovery of cloudy peritoneal dialysate and abdominal pain. Ceftazidime and cefazolin sodium were immediately given intravenously as an empirical antibiotic regimen. After detecting Serratia marcescens in the peritoneal diasate culture, the treatment was switched to ceftazidime and levofloxacin. The routine examination of peritoneal dialysate showed a significant decrease in white blood cells, the peritoneal dialysate became clear, and the peritoneal dialysis catheter was retained. The patient was treated for 2 weeks and treated with oral antibiotics for 1 week. It is necessary to further strengthen the hygiene of work environment to prevent Serratia marcescens infection in peritoneal dialysis patients. We recommend that patients with Serratia marcescens associated peritonitis should be treated with a combination of antibiotics as early as possible empirically, and at the same time, the peritoneal dialysis fluid culture should be improved, and the antibiotic regimen should be timely adjusted according to the drug sensitivity results. For patients with clinical symptoms for more than 3 days, considering the strong virulence of Serratia marcescens, whether to use meropenem directly or not can provide a reference for clinical decision-making. Further clinical studies are needed to achieve more precise anti-infective treatment.
Assuntos
Antibacterianos , Diálise Peritoneal , Peritonite , Infecções por Serratia , Serratia marcescens , Humanos , Serratia marcescens/isolamento & purificação , Masculino , Peritonite/microbiologia , Peritonite/tratamento farmacológico , Adulto , Infecções por Serratia/microbiologia , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Diálise Peritoneal/efeitos adversos , Resultado do Tratamento , Remoção de Dispositivo , Levofloxacino/uso terapêutico , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , Cefazolina/uso terapêuticoRESUMO
PURPOSE: Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy (PLWPA) in our institutional empirical antibiotic guidelines. Due to a global aztreonam shortage in December 2022, the antimicrobial stewardship unit recommended ceftazidime as a substitute. There is a paucity of real-world data on the safety profile of ceftazidime in PLWPA. Hence, we evaluated tolerability outcomes of ceftazidime use in PLWPA. METHODS: This retrospective cohort study compared PLWPA in Singapore General Hospital who received aztreonam (October 2022-December 2022) or ceftazidime (December 2022-February 2023). Patients were stratified according to their risk of allergic reaction (AR) based on history of penicillin allergy. The severity of AR was based on the Delphi study grading system. The primary outcome was development of AR after initiation of aztreonam or ceftazidime. The secondary tolerability outcomes include hepatotoxicity and neurotoxicity. FINDINGS: There were 168 patients in the study; 69 were men (41.1%) and the median age was 69 years (interquartile range: 59-76 years). Incidence of AR was statistically similar in both arms: 1 of 102 patients (0.98%) in the aztreonam arm vs 2 of 66 patients (3.03%) in the ceftazidime arm (P = 0.33). The patient in the aztreonam arm was deemed at medium risk of having an AR and developed localized rashes (grade 1). Both patients in the ceftazidime arm were deemed at high risk of AR and developed localized skin reaction (grade 1). Hepatotoxicity was observed in 1 patient prescribed aztreonam. No patients in the ceftazidime arm developed adverse events. IMPLICATIONS: Ceftazidime appears to be better tolerated and cheaper compared with aztreonam in PLWPA, and serves as an antimicrobial stewardship strategy to conserve broader-spectrum antibiotics use.
Assuntos
Antibacterianos , Aztreonam , Ceftazidima , Hipersensibilidade a Drogas , Penicilinas , Humanos , Aztreonam/efeitos adversos , Aztreonam/administração & dosagem , Ceftazidima/efeitos adversos , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , Masculino , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Penicilinas/efeitos adversos , Estudos de Coortes , SingapuraRESUMO
A man in his 40s with type 2 diabetes mellitus had persistent right-sided watery nasal discharge for 6 months following cerebrospinal fluid (CSF) leak repair at another hospital, prompting his visit to us due to recurring symptoms. Imaging revealed a CSF leak from the mid-clivus for which revision endoscopic CSF leak repair was done. Regrettably, he developed postoperative meningitis caused by multidrug-resistant (MDR) Klebsiella pneumoniaeManaging this complex case was a challenging task due to the pathogen's resistance to conventional drugs and the scarcity of scientific evidence. We initiated a culture-guided combination regimen with ceftazidime, avibactam, aztreonam and tigecycline. This decision stemmed from meticulous literature review and observed antibiotic synergy while testing for this organism.After 4 weeks of vigilant treatment, the patient's symptoms improved significantly, and CSF cultures were sterile. We present our approach to effectively confront and manage a challenging instance of postoperative MDR bacterial meningitis.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Infecções por Klebsiella , Klebsiella pneumoniae , Meningites Bacterianas , Humanos , Masculino , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Antibacterianos/uso terapêutico , Vazamento de Líquido Cefalorraquidiano/terapia , Adulto , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , Fossa Craniana Posterior/cirurgia , Aztreonam/uso terapêutico , Aztreonam/administração & dosagem , Tigeciclina/uso terapêutico , Tigeciclina/administração & dosagem , Combinação de Medicamentos , Compostos AzabicíclicosRESUMO
OBJECTIVE: To present and evaluate the treatment of ciprofloxacin-resistant Pseudomonas mastoid cavity otorrhea with a ceftazidime thermosensitive poloxamer gel. STUDY DESIGN: A retrospective clinical capsule report. PATIENTS: Three patients diagnosed with ciprofloxacin-resistant Pseudomonas otorrhea in the setting of a previous canal-wall-down mastoidectomy between March 2019 and June 2023 visiting our tertiary care institution were retrospectively reviewed. INTERVENTION: Application of a 2% ceftazidime thermosensitive poloxamer gel to mastoid cavity. MAIN OUTCOME MEASURES: No evidence of disease during microscopic inspection of the ear within a month of initial treatment or bacterial eradication on subsequent culture. RESULTS: Two patients had complete resolution of symptoms and achieved a safe and dry ear after topical application of the hydrogel. The second patient had pseudomonal eradication on culture, but persistent otorrhea due to other multidrug-resistant bacteria and an anatomically unfavorable mastoid cavity, which ultimately resolved after revision surgery. CONCLUSIONS: This small case series suggests that topical treatment of mastoid cavity otorrhea with a 2% ceftazidime poloxomer gel is a potential therapeutic avenue in patients with ciprofloxacin-resistant Pseudomonas .
Assuntos
Antibacterianos , Ceftazidima , Ciprofloxacina , Géis , Poloxâmero , Infecções por Pseudomonas , Humanos , Ciprofloxacina/uso terapêutico , Ciprofloxacina/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Processo Mastoide/cirurgia , Farmacorresistência Bacteriana , Otite Média com Derrame/tratamento farmacológico , Otite Média com Derrame/microbiologia , Otite Média com Derrame/cirurgia , Idoso , Adulto , Administração TópicaRESUMO
We present a case of endogenous endophthalmitis with urinary tract infection (UTI) caused by group B Streptococcus (GBS). An 86-year-old female initially presented with ocular pain and sudden visual disturbance of the left eye. The patient did not complain of other symptoms and had no history of recent ocular surgery or trauma. Endogenous endophthalmitis was clinically diagnosed based on ophthalmic examination, history, and lab results showing systemic infection. A few days later, GBS was identified in her aqueous humor, blood, and urine cultures. Intravitreal ceftazidime and vancomycin injections, as well as fortified ceftazidime and vancomycin eye drops, were used immediately after clinical diagnosis. However, the symptoms worsened despite repeated intravitreal injections, so evisceration was performed. Endogenous endophthalmitis caused by GBS is very virulent and may present without evident systemic symptoms. The early recognition of the disease and systemic work up, followed by prompt treatment, is necessary.
Assuntos
Antibacterianos , Endoftalmite , Infecções Estreptocócicas , Streptococcus agalactiae , Infecções Urinárias , Humanos , Feminino , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Infecções Urinárias/complicações , Idoso de 80 Anos ou mais , Endoftalmite/diagnóstico , Endoftalmite/microbiologia , Endoftalmite/tratamento farmacológico , Streptococcus agalactiae/isolamento & purificação , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/diagnóstico , Antibacterianos/uso terapêutico , Vancomicina/uso terapêutico , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagemRESUMO
BACKGROUND: Vancomycin and tobramycin have traditionally been used in antibiotic spacers. In 2020, our institution replaced tobramycin with ceftazidime. We hypothesized that the use of ceftazidime/vancomycin (CV) in antibiotic spacers would not lead to an increase in treatment failure compared to tobramycin/vancomycin (TV). METHODS: From 2014 to 2022, we identified 243 patients who underwent a stage I revision for periprosthetic joint infection. The primary outcome was a recurrent infection requiring antibiotic spacer exchange. We were adequately powered to detect a 10% difference in recurrent infection. Patients who had a prior failed stage I or two-stage revision for infection, acute kidney injury prior to surgery, or end-stage renal disease were excluded. Given no other changes to our spacer constructs, we estimated cost differences attributable to the antibiotic change. Chi-square and t-tests were used to compare the two groups. Multivariable logistic regressions were utilized for the outcomes. RESULTS: The combination of TV was used in 127 patients; CV was used in 116 patients. Within one year of stage I, 9.8% of the TV group had a recurrence of infection versus 7.8% of the CV group (P = .60). By final follow-up, results were similar (12.6 versus 8.6%, respectively, P = .32). Adjusting for potential risk factors did not alter the results. Cost savings for ceftazidime versus tobramycin are estimated to be $68,550 per one hundred patients treated. CONCLUSIONS: Replacing tobramycin with ceftazidime in antibiotic spacers yielded similar periprosthetic joint infection eradication success at a lower cost. While larger studies are warranted to confirm these efficacy and cost-saving results, our data justifies the continued investigation and use of ceftazidime as an alternative to tobramycin in antibiotic spacers.
Assuntos
Antibacterianos , Ceftazidima , Infecções Relacionadas à Prótese , Tobramicina , Vancomicina , Humanos , Tobramicina/administração & dosagem , Tobramicina/economia , Vancomicina/economia , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico , Ceftazidima/administração & dosagem , Ceftazidima/economia , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/economia , Antibacterianos/economia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Reoperação/economia , Resultado do Tratamento , Estudos Retrospectivos , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/instrumentaçãoRESUMO
OBJECTIVES: The use of extracorporeal membrane oxygenation (ECMO) may alter blood levels of several drugs, including antibiotics, leading to under dosing of these drugs and thus to potential treatment failure. No data exist on pharmacokinetics of new antimicrobial, in particular ceftazidime/avibactam. We therefore perform this study to evaluate ceftazidime/avibactam blood levels in ECMO patients and find factors associated with underdosing. METHODS: Retrospective observational study of patients on ECMO having received ceftazidime/avibactam and in whom trough blood levels of ceftazidime and avibactam were available. Main outcome measurement was the number of patients with ceftazidime and avibactam blood levels above predefined cut-off values, derived from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa, namely 8â mg/L for ceftazidime and 4â mg/L for avibactam, and explored factors associated with underdosing. RESULTS: Twenty-three ceftazidime/avibactam trough levels were available in 14 ECMO patients, all of them having received veno-venous ECMO for SARS-CoV-2-associated pneumonia. Although ceftazidime levels were above 8â mg/L in all except one patient, nine (39%) of the avibactam dosages were below 4â mg/L. Increased renal clearance (creatinine clearanceâ>â130â mL/min) was the main factor associated with under dosing, since 7 out of the 10 dosages below the predefined cut-offs were measured in patients with this condition. CONCLUSIONS: In ECMO patients receiving ceftazidime/avibactam, ceftazidime and avibactam serum levels are above EUCAST breakpoints in most cases, justifying the use of normal dosing in ECMO patients. Increased renal clearance may lead to ceftazidime and avibactam under dosing.
Assuntos
Antibacterianos , Compostos Azabicíclicos , Ceftazidima , Combinação de Medicamentos , Oxigenação por Membrana Extracorpórea , Humanos , Ceftazidima/farmacocinética , Ceftazidima/administração & dosagem , Ceftazidima/uso terapêutico , Ceftazidima/sangue , Compostos Azabicíclicos/farmacocinética , Compostos Azabicíclicos/administração & dosagem , Compostos Azabicíclicos/uso terapêutico , Compostos Azabicíclicos/sangue , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/sangue , Adulto , Idoso , Pseudomonas aeruginosa/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Enterobacteriaceae/efeitos dos fármacosRESUMO
Citrobacter koseri es un bacilo gramnegativo que causa endoftalmitis de forma muy infrecuente y agresiva, asociando mal pronóstico visual. Solo el 6% de las endoftalmitis son por gramnegativos y nuestro germen representa un pequeño porcentaje. Presentamos un varón de 65 años que trabaja en un laboratorio de animales. Acude a urgencias por pérdida de visión del ojo izquierdo debido a una hemorragia vítrea y desprendimiento de retina. Se practica una vitrectomía y 3 días después, desarrolla una endoftalmitis. Se realiza tratamiento intravítreo con inyecciones de vancomicina y ceftazidima así como tratamiento antibiótico tópico. Veinticuatro horas después, regresa con perforación corneal y una extrusión del cristalino. Ante la gravedad del cuadro se realiza una evisceración. El cultivo de las muestras confirman el microorganismo. Suponemos que la puerta de entrada del germen fueron las esclerotomías por el material de sutura expuesto, tras la manipulación de heces de roedores.(AU)
Citrobacter koseri is a bacillus that causes infrequent endophthalmitis. Six percent of cultures in endophthalmitis are Gram -, and as in these, Citrobacter koseri is associated with a poor visual prognosis. We present a 65-year-old man who works in an animal laboratory. He went to emergencies with loss of vision in his left eye due to a vitreous hemorrhage. A vitrectomy was performed and 3 days later, endophthalmitis was diagnosed. Vancomycin and ceftazidime were applied in eye drops and in two intravitreal injections. Twenty-four hours later he returned with a lens extrusion. Due to the severity of the condition, an evisceration was performed. Subsequently, the samples confirm the microorganism. We assume that the entry point for the bacterium was the sclerotomies through the exposed suture material, after handling rodent feces.(AU)
Assuntos
Humanos , Masculino , Idoso , Citrobacter koseri , Vitrectomia , Descolamento Retiniano , Hemorragia Vítrea , Vancomicina/administração & dosagem , Ceftazidima/administração & dosagem , Pacientes Internados , Exame Físico , Oftalmologia , Cegueira , Endoftalmite , AnimaisRESUMO
OBJECTIVE: To evaluate and compare the pharmacokinetic parameters of SC ceftazidime administered at 20 and 40 mg/kg to red-eared sliders. ANIMALS: 8 adult red-eared sliders (Trachemys scripta elegans). METHODS: In a sequential, 2-period study with a 3-week washout period between treatments, ceftazidime was administered SC to turtles at 20 and 40 mg/kg. Blood samples were collected from the subcarapacial sinus at 0, 24, 48, 72, 96, and 120 hours after ceftazidime administration. Plasma ceftazidime concentrations were quantified using reversed-phase HPLC. RESULTS: Mean plasma half-life after 20- and 40-mg/kg dosing was 39.75 ± 8.0 hours and 33.03 ± 6.56 hours, respectively. Mean maximum plasma concentration after 20- and 40-mg/kg dosing was 71.0 ± 15.93 µg/mL and 120.0 ± 30.62 µg/mL, respectively. Mean plasma ceftazidime concentrations remained ≥ 8 µg/mL, the theoretical MIC for various reptile pathogens for all time points. CLINICAL RELEVANCE: Results indicate that ceftazidime dosed at either 20 or 40 mg/kg produces plasma concentrations exceeding the theoretical MIC of various reptile pathogens for at least 120 hours. An ideal dosing interval could not be determined, as all plasma concentrations remained above the threshold of interest for all time points. Follow-up studies should focus on establishing a dosing interval and more rigorous monitoring for potential adverse effects.
Assuntos
Antibacterianos , Ceftazidima , Tartarugas , Animais , Tartarugas/sangue , Ceftazidima/farmacocinética , Ceftazidima/administração & dosagem , Ceftazidima/sangue , Antibacterianos/farmacocinética , Antibacterianos/sangue , Antibacterianos/administração & dosagem , Injeções Subcutâneas/veterinária , Meia-Vida , Área Sob a Curva , Masculino , Feminino , Relação Dose-Resposta a DrogaRESUMO
Intrastromal antibiotic injections are a type of treatment that can be very useful in bacterial keratitis refractory to topical antibiotics. We present the case of a 44-year-old woman with an infiltrate in a laser in situ keratomiuleusis (LASIK) flap and growth of Achromobacter xylosoxidans, who was treated with topical ceftazidime for 1 month. However, after discontinuation of the antibiotic, there was a worsening with growth of the same germ. Topical treatment was reintroduced and, due to suspicion of germ reservoir, it was decided to give three cycles of intrastromal ceftazidime injections, the last one also with moxifloxacin, with good results. After 4 months asymptomatic and without treatment at the moment, no signs of recurrence have been observed. This case supports the usefulness of intraestromal injections in refractory cases to the topical medication.
Assuntos
Achromobacter denitrificans , Antibacterianos , Ceftazidima , Infecções por Bactérias Gram-Negativas , Ceratomileuse Assistida por Excimer Laser In Situ , Retalhos Cirúrgicos , Humanos , Feminino , Adulto , Achromobacter denitrificans/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , Moxifloxacina/uso terapêutico , Moxifloxacina/administração & dosagem , Infecções Oculares Bacterianas/tratamento farmacológico , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Substância Própria , Complicações Pós-Operatórias/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/administração & dosagemRESUMO
PURPOSE: Multidrug-resistant (MDR) infections are challenging to treat due to underlying patient conditions, pathogen characteristics, and high antibiotic resistance rates. As newer antibiotic therapies come to market, limited data exist about their real-world utilization. METHODS: This was a national retrospective cohort study of ceftazidime/avibactam (approved in 2015) utilization among inpatients from the Veterans Affairs (VA) Healthcare System, from 2015 through 2021. Joinpoint regression was used to estimate time trends in utilization. RESULTS: Ceftazidime/avibactam use increased by 52.3% each year (days of therapy per 1,000 bed days; 95% confidence interval, 12.4%-106.4%). We identified 1,048 unique predominantly male (98.3%) and white (66.2%; Black, 27.7%) patients treated with ceftazidime/avibactam, with a mean (SD) age of 71.5 (11.9) years. The most commonly isolated organisms were Pseudomonas aeruginosa (36.3%; carbapenem resistant, 80.6%; MDR, 65.0%) and Klebsiella species (34.1%; carbapenem resistant, 78.4%; extended-spectrum cephalosporin resistant, 90.7%). Common comorbid conditions included hypertension (74.8%), nervous system disorders (60.2%), diabetes mellitus (48.7%), and cancer (45.1%). Median time to ceftazidime/avibactam initiation from admission was 6 days, with a median of 3 changes in therapy before ceftazidime/avibactam initiation and a subsequent median length of inpatient stay of 14 days (median of 8 days of ceftazidime/avibactam therapy). Treatment heterogeneity was high, both before ceftazidime/avibactam initiation (89.6%) and during ceftazidime/avibactam treatment (85.6%), and common concomitant antibiotics included vancomycin (41.4%), meropenem (24.1%), cefepime (15.2%), and piperacillin/tazobactam (15.2%). The inpatient mortality rate was 23.6%, and 20.8% of patients had a subsequent admission with ceftazidime/avibactam treatment. CONCLUSION: Utilization of ceftazidime/avibactam increased from 2015 to 2021 in the national VA Healthcare System. Ceftazidime/avibactam was utilized in complex, difficult-to-treat patients, with substantial treatment heterogeneity and variation in the causative organism and culture sites.
Assuntos
Antibacterianos , Compostos Azabicíclicos , Ceftazidima , Combinação de Medicamentos , United States Department of Veterans Affairs , Humanos , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , Masculino , Estudos Retrospectivos , Feminino , Compostos Azabicíclicos/uso terapêutico , Idoso , Pessoa de Meia-Idade , Estados Unidos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Pacientes Internados , Idoso de 80 Anos ou mais , Estudos de Coortes , VeteranosRESUMO
The spread of multidrug-resistant Gram-negative bacterial infections is a significant issue for worldwide public health. Gram-negative organisms regularly develop resistance to antibiotics, especially to ß-lactam antimicrobials, which can drastically restrict the number of therapies. A third-generation cephalosporin and the non-ß-lactam ß-lactamase inhibitor avibactam, which exhibits broad-spectrum ß-lactamase inhibition in vitro, are combined to form ceftazidime-avibactam (CAZ-AVI). In this narrative review, we summarize data on pharmacokinetic (PK) parameters for CAZ-AVI in both animal and human models of pneumonia, as well as in healthy individuals. We assessed current literature performing an extensive search of the literature, using as search words 'CAZ-AVI', 'pharmacokinetics', 'pneumonia', 'lung', and 'epithelial lining fluid'. Overall, lung exposure studies of CAZ-AVI revealed that the epithelial lining fluid penetration ranges between 30% and 35% of plasma concentration. Despite the fair lung penetration of CAZ-AVI, this antimicrobial agent has a pivotal role in managing patients with multi-drug resistant Gram-negative pneumonia, however further studies are needed to better assess its PK profile.
Assuntos
Antibacterianos , Compostos Azabicíclicos , Ceftazidima , Combinação de Medicamentos , Pulmão , Humanos , Compostos Azabicíclicos/farmacocinética , Compostos Azabicíclicos/uso terapêutico , Animais , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Ceftazidima/farmacocinética , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , Pulmão/metabolismo , Cuidados Críticos/métodos , Modelos Animais de Doenças , Pneumonia Bacteriana/tratamento farmacológico , Inibidores de beta-Lactamases/farmacocinética , Inibidores de beta-Lactamases/uso terapêutico , Pneumonia/tratamento farmacológicoRESUMO
We report a fatal case of New Delhi metallo-ß-lactamase (NDM)-producing Escherichia coli in a bacteremic patient with sequential failure of aztreonam plus ceftazidime-avibactam followed by cefiderocol. Acquired resistance was documented phenotypically and mediated through preexisting and acquired mutations. This case highlights the need to rethink optimal treatment for NDM-producing organisms.
Assuntos
Antibacterianos , Compostos Azabicíclicos , Aztreonam , Bacteriemia , Cefiderocol , Ceftazidima , Cefalosporinas , Combinação de Medicamentos , Infecções por Escherichia coli , Escherichia coli , Falha de Tratamento , beta-Lactamases , Humanos , Compostos Azabicíclicos/uso terapêutico , Compostos Azabicíclicos/administração & dosagem , beta-Lactamases/genética , beta-Lactamases/metabolismo , Aztreonam/uso terapêutico , Aztreonam/administração & dosagem , Aztreonam/farmacologia , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/enzimologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Evolução Fatal , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Cefalosporinas/uso terapêutico , Cefalosporinas/administração & dosagem , Testes de Sensibilidade Microbiana , Masculino , Farmacorresistência Bacteriana MúltiplaRESUMO
INTRODUCTION: Carbapenem-resistant Enterobacterales (CRE) due to Metallo-ß-lactamase (MBL) production are treated with either polymyxins or the novel combination of ceftazidime-avibactam and aztreonam (AA). This study aims to evaluate the 30-day mortality of AA in patients with BSI caused by MBL-CRE infections. METHODOLOGY: In this systematic review and meta-analysis, all articles up to June 2023 were screened using search terms like 'CRE', 'MBL', 'AA' and 'polymyxins'. The risk ratio for AA vs polymyxins was pooled using a random-effect model, and the results were represented by a point estimate with a 95% confidence interval. RESULTS: After removing the duplicates, the titles and abstracts of 455 articles were screened, followed by a full-text screening of 50 articles. A total of 24 articles were included for systematic review, and four comparative studies were included in the meta-analysis. All four studies had a moderate or serious risk of bias. The pooled risk ratio for 30-day mortality for AA vs. polymyxins was 0.51 (95%CI: 0.34-0.76), p < 0.001. There was no significant heterogeneity. CONCLUSION: The meta-analysis from studies with a high risk of bias shows that AA is associated with lesser 30-day mortality when compared to polymyxins in patients with MBL-producing CRE BSI. Registration with PROSPERO- CRD42023433608.
Assuntos
Antibacterianos , Compostos Azabicíclicos , Aztreonam , Enterobacteriáceas Resistentes a Carbapenêmicos , Ceftazidima , Infecções por Enterobacteriaceae , Humanos , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/administração & dosagem , Aztreonam/farmacologia , Aztreonam/administração & dosagem , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , beta-Lactamases/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Ceftazidima/farmacologia , Ceftazidima/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologiaRESUMO
INTRODUCCIÓN: Las bacteriemias por Enterobacterales productores de carbapenemasa KPC (EPC-KPC) presentan una mortalidad elevada y opciones terapéuticas limitadas. OBJETIVOS: Describir y comparar la evolución de los pacientes con bacteriemia por EPC-KPC tratados con ceftazidima/avibactam (CA) frente a otros antimicrobianos (OA). PACIENTES Y MÉTODOS: Estudio prospectivo y retrospectivo de casos y controles. Se incluyeron pacientes adultos con bacteriemia por EPC-KPC, con una proporción entre casos tratados con CA y controles tratados con OA. de 1:2. Se analizaron variables clínicas, epidemiológicas y de evolución. RESULTADOS: Se incluyeron 48 pacientes (16 CA y 32 OA). Los casos se encontraban más frecuentemente neutropénicos (50 vs.16%, p = 0,012); asimismo, presentaron medianas de score de APACHE II más altas y de score de Pitt más bajas. El 65% de la cohorte total presentó un foco clínico y Klebsiellapneumoniae fue el microorganismo más frecuentemente aislado. Los casos recibieron una mayor proporción de tratamiento antimicrobiano empírico adecuado (81 vs. 53%, p = 0,05). La antibioterapia dirigida en casos y controles fue combinada en 38 y 91%, p = 0,009. Los casos presentaron menor mortalidad al día 7 y al día 30 relacionada a infección (0 vs. 22%, p = 0,04 y 0 vs. 34%, p = 0,008). Solo los controles desarrollaron shock, ingresaron a la unidad de cuidados intensivos y presentaron bacteriemia de brecha. CONCLUSIÓN: CA mostró beneficio clínico frente a OA para el tratamiento de pacientes con bacteriemia por EPC-KPC.
BACKGROUND: KPC-producing Enterobacterales bacteremia (KPCCPE) is associated with a high mortality rate and limited therapeutic options. AIM: To describe and compare the outcome of patients with KPC-CPE bacteremia treated with ceftazidime/avibactam (CA) versus other antibiotics (OA). METHODS: Prospective and retrospective cases and control study performed in adult patients with KPC-CPE bacteremia, with a 1:2 ratio between cases treated with CA. and controls treated with OA. Clinical, epidemiological, and outcome variables were analyzed. RESULTS: Forty-eight patients (16 CA and 32 OA) were included. Cases were more frequently neutropenic (50 vs. 16%, p = 0.012), presented higher median APACHE II score and lower Pitt score. Of the total cohort, 65% had a clinical source, and Klebsiella pneumoniae was the most frequently isolated microorganism. Cases received more adequate empirical antibiotic treatment (81 vs. 53%, p = 0.05). Targeted antibiotic therapy in cases and controls was combined in 38 and 91%, p = 0.009. Cases had a lower 7-day mortality and 30-day infection-related mortality (0 vs. 22%, p = 0.04 and 0 vs. 34%, p = 0.008). Only controls developed shock, were admitted to the intensive care unit, and had breakthrough bacteremia. CONCLUSION: CA. showed clinical benefit over OA in the treatment of patients with EPC-KPC bacteremia.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Ceftazidima/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Enterobacteriaceae/tratamento farmacológico , Compostos Azabicíclicos/uso terapêutico , Antibacterianos/uso terapêutico , Proteínas de Bactérias , beta-Lactamases , Estudos de Casos e Controles , Ceftazidima/administração & dosagem , Evolução Clínica , Estudos Prospectivos , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Combinação de Medicamentos , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/mortalidade , Compostos Azabicíclicos/administração & dosagem , Inibidores de beta-Lactamases , Antibacterianos/administração & dosagemRESUMO
ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021 y ampliada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 97-IETSI-ESSALUD2022, se ha elaborado el presente dictamen, el cual expone la evaluación de la eficacia y seguridad de ceftazidima-avibactam en pacientes pediátricos de 3 meses a más con sepsis causada por bacterias Gram-negativas productoras de carbapenemasas y resistentes a colistina. Así, el Dr. Michael Algio Quispe Huarcaya y la Dra. Mabel Rubi Carhuana Salazar, médicos especialistas en gastroenterología pediátrica del Hospital Nacional Edgardo Rebagliati Martins (HNERM), siguiendo la Directiva N° 003-IETSIESSALUD-2016, enviaron al Instituto de Evaluación de Tecnologías en Salud e Investigación IETSI las solicitudes de autorización de uso del producto farmacéutico ceftazidima-avibactam no incluido en el Petitorio Farmacológico de EsSalud. ASPECTOS GENERALES: La sepsis se define como una disfunción orgánica potencialmente mortal causada por una respuesta desregulada del huésped a la infección (Pomerantz y Weiss 2022). Se caracteriza por un síndrome de respuesta inflamatoria sistémica (SRIS) en respuesta a una infección, que en pacientes pediátricos consiste en: i) temperatura anormal' y/o recuento anormal de leucocitos, más ii) el ritmo cardiaco anormal2y/o frecuencia respiratoria anormalmente alta' (DynaMed 2022). La sepsis no tratada tempranamente, puede ocasionar daño irreversible a los tejidos, shock séptico, insuficiencia orgánica múltiple y poner en riesgo la vida (OPS 2022). Se estima que la mortalidad hospitalaria en pacientes pediátricos con sepsis es 2 % al 10 %, mientras que en pacientes pediátricos cuya sepsis se complica a sepsis grave (sepsis con disfunción de órganos diana) o shock séptico (sepsis con disfunción cardiovascular), la mortalidad es de 14 % al 50 % (DynaMed 2022; Weiss et al. 2020). METODOLOGÍA Se realizó una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad de C-A, en comparación con la mejor terapia de soporte, en pacientes pediátricos de 3 meses a más con sepsis causada por bacterias Gram-negativas productoras de carbapenemasas y resistentes a colistina (población objetivo). La búsqueda bibliográfica se llevó a cabo en las bases de datos: PubMed, The Cochrane Library, Web of Science y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Scottish Medicines Consortium (SMC), el Scottish Intercollegiate Guidelines Network (SIGN), el Institute for Quality and Efficiency in Healthcare (IQWiG por sus siglas en alemán), la International Database of GRADE Guideline, el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Guidelines International Network (GIN), el National Health and Medical Research Council (NHMRC), la Cancer Guidelines Database, el New Zealand Guidelines Group (NZGG), el Instituto de Evaluación Tecnológica en Salud (IETS), el Instituto de Efectividad Clínica y Sanitaria (IECS), la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), la Organización Mundial de la Salud y el Ministerio de Salud del Perú (MINSA). Además, se realizó una búsqueda de GPC de las principales sociedades o instituciones especializadas en infectología, tales como: la European Society of Clinical Microbiology and Infectious Diseases (ESCMID), la European Society of Intensive Care Medicine (ESICM), la Pediatric Infectious Diseases Society (PIDS) y la Infectious Diseases Society of America (IDSA). Finalmente, se realizó una búsqueda en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o que no hayan sido publicados aún. RESULTADOS: Luego de la búsqueda bibliográfica hasta noviembre de 2022, se identificaron dos GPC elaboradas por la IDSA (Tamma et al. 2022) y la ESCMID (Paul et al. 2022), una ETS elaborada por NICE (NICE 2022) y un estudio observacional publicado por Wang et al. (Wang et al. 2022). Cabe mencionar que se excluyeron un ECA (Bradley et al. 2019) y dos GPC (Weiss et al. 2020; NICE 2017). Este ECA fue excluido porque evaluó pacientes pediátricos con infección urinaria complicada donde no se describe si los pacientes presentaron o no sepsis. Además, no se especifica si dichas infecciones fueron o no por bacterias productoras de carbapenemasas o al menos si fueron o no resistentes a carbapenémicos; por lo tanto, no brinda información que permita responder a la pregunta PICO del presente dictamen. Respecto a las GPC, estas dos guías (Weiss et al. 2020; NICE 2017) fueron excluidas porque sus recomendaciones no están dirigidas a la población objetivo del presente dictamen (pacientes con sepsis por bacterias gram-negativas productoras de carbapenemasas). CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de ceftazidima-avibactam para pacientes pediátricos de 3 meses a más con sepsis causada por bacterias Gram-negativas productoras de carbapenemasas y resistentes a colistina, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud, según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.
Assuntos
Humanos , Lactente , Ceftazidima/administração & dosagem , Colistina/efeitos adversos , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Eficácia , Análise Custo-BenefícioRESUMO
Introdução: A pandemia de COVID-19 fez aumentar a demanda de medicamentos utilizados em hospitais, como a Ceftazidima + Avibactam. Nesse contexto, a Central de Misturas Intravenosas (CMIV) de um hospital público universitário passou a unitarizar as doses prescritas. O objetivo deste trabalho foi avaliar o impacto da unitarização no consumo deste antibacteriano de alto custo em um hospital público universitário. Métodos: Trata-se de uma análise farmacoeconômica de custos diretos, sobre a utilização de frascos-ampola de Ceftazidima + Avibactam no período de 01/07/2020 a 31/05/2021. Foram unitarizadas todas as doses que correspondiam a uma fração da dose total do frasco-ampola, em Cabine de Segurança Biológica classe II B2. Os frascos-ampola foram utilizados à exaustão, através do compartilhamento e organização dos horários de manipulação. Resultados: O número total de preparos realizados pela CMIV do referido hospital no período foi de 837. O consumo projetado sem a centralização dos preparos seria de 837 (um frasco por dose). Entretanto, o consumo real foi de 437 frascos. A eficiência de unitarização foi de 101%, com economia real de 400 frascos (R$ 244.832,00) para a instituição. Conclusão: A pandemia de COVID-19 sobrecarregou os sistemas de saúde do mundo todo, sendo que a atuação farmacêutica foi fundamental para garantir o acesso aos medicamentos essenciais. A CMIV assumiu a unitarização da Ceftazidima + Avibactam, antibiótico em risco de desabastecimento, gerando um consumo 47,8% menor, contribuindo para o acesso deste medicamento de forma ininterrupta durante os 11 meses avaliados na referida instituição.
Introduction: COVID-19 pandemic has increased the demand for drugs used in hospitals, such as Ceftazidime + Avibactam. In this context, the Central of Intravenous Admixtures (CMIV) of a public university hospital started to unitarize the prescribed doses. The objective of this study was to evaluate the impact of unitarization on the consumption of this high-cost antibacterial in a public university hospital. Methods: This is a pharmacoeconomic analysis of direct costs, on the Ceftazidime + Avibactam vials use, in the period from 07/01/2020 to 05/31/2021. All doses that corresponded to a fraction of the entire vial were unitarized in a Class II B2 Biological Safety Cabin. The vials were used to exhaustion, by sharing them, and organizing the manipulation schedules. Results: The total number of preparations made by the CMIV of that hospital in the period was 837 doses. The projected consumption would be 837 vials (one vial per dose). However, the actual consumption was 437 vials. The unitarization efficiency was of 101%, with real savings of 400 vials (R$ 244,832.00) for the institution. Conclusion: COVID-19 pandemic has overburdened health systems around the world, and pharmaceutical actions have been fundamental to guaranteeing access to essential medicines. CMIV took over the unitarization of Ceftazidime + Avibactam, an antibiotic at risk of shortages, leading to a 47.8% lower consumption, contributing to uninterrupted access to this drug during the 11 months evaluated at that institution.
Assuntos
Farmacêuticos/provisão & distribuição , Preparações Farmacêuticas/provisão & distribuição , Ceftazidima/administração & dosagem , Antibacterianos/administração & dosagem , Conhecimentos, Atitudes e Prática em Saúde , Saúde Pública/métodos , Acesso a Medicamentos Essenciais e Tecnologias em Saúde , COVID-19/prevenção & controleRESUMO
To provide direction for clinical application and pharmaceutical exploitation, the in vitro activity of sulbactam compounds and PIP/TAZ 8 : 1 against clinical isolates of Gram-negative bacteria (GNB, n = 976) was evaluated according to Clinical and Laboratory Standards Institute (CLSI) 2019. By minimal inhibitory concentrations (MICs), the resistance rate of all GNB to AMP/SBT 2 : 1 (56.9-100%) was significantly higher than other drugs, except the resistance rate of Acinetobacter baumannii (Aba, n = 204) to piperacillin/tazobactam (PIP/TAZ 8 : 1, 78.4%) which was close to it (76.5%). Additionally, the resistance rate of Aba to other compounds except AMP/SBT 2 : 1 differed greatly, but that of Klebsiella pneumonia (Kpn, n = 205) varied rarely. In addition, Escherichia coli (Eco, n = 204) and Kpn demonstrated low and high resistance rates, respectively. Compared with cefoperazone/sulbactam (CPZ/SBT 2 : 1), PIP/TAZ 8 : 1 had advantage in anti-Eco (RR = 0.5and OR = 2.17) and anti-Kpn activity (RR = 0.88and OR = 1.27), while its activity against Pseudomonas aeruginosa (Pae: n = 194, RR = 0.91, and OR = 1.12), Aba (RR = 1.31 and OR = 0.41), and other Enterobacteriaceae (other Ebc: n = 169, RR = 1.40, and OR = 0.62) was not better than CPZ/SBT 2 : 1. Although it had advantage against Eco (RR = 0.60 and OR = 1.78), Pae (RR = 0.67 and OR = 1.63), and Aba (RR = 0.70 and OR = 2.05), the inhibition effect of piperacillin/sulbactam (PIP/SBT 2 : 1) against Kpn (RR = 0.94 and OR = 1.12) and other Ebc was just similar with CPZ/SBT 2 : 1 (RR = 0.93 and OR = 1.10). Furthermore, the anti-Eco (RR = 0.70 and OR = 1.50), anti-Kpn (RR = 0.89 and OR = 1.24), and anti-Pae (RR = 0.74 and OR = 1.46) activities of ceftazidime/sulbactam (CAZ/SBT 1 : 1) had a weak advantage, while its activity against Aba (RR = 0.94 and OR = 1.15) and other Ebc (RR = 0.79 and OR = 1.36) was just close to CPZ/SBT 2 : 1. Moreover, the inhibitory effect of PIP/SBT 1 : 1 against all tested clinical species was more active than CPZ/SBT 2 : 1, while that of CAZ/SBT 2 : 1 against all species of bacteria analyzed was weaker than the controls.