RESUMEN
RATIONALE: Bacterascites are a rare complication of cesarean sections (C/S). Here, we report the case of a patient with bacterascites after an emergent C/S. PATIENT CONCERN: A 41-year-old female reported diffuse abdominal tightness and pain for a week after C/S, who received C/S at 38 4/7 weeks due to superimposed preeclampsia and prolonged labor. DIAGNOSES: Bacterascites caused by Salmonella species after C/S was diagnosed. INTERVENTIONS: Initial treatment included cefmetazole and metronidazole. On day 2, paracentesis was performed, followed by albumin and hydroxyethyl starch administration. By day 3, the patient developed pulmonary edema, necessitating Lasix administration. On day 6, ascites culture revealed Salmonella species resistant to third-generation cephalosporins, leading to meropenem therapy adjustment. This resulted in improved symptoms. Meropenem was continued for 14 days to complete the treatment regimen. OUTCOMES: Follow-up ultrasonography revealed a decrease in ascites. As the patient clinical condition improved, she was discharged on day 20 and scheduled for outpatient department follow-up. No recurrence of ascites was observed during the subsequent follow-up period of 3 months. No ascites were noted 8 days after discharge. LESSONS: Postoperative bacterascites with Salmonella were diagnosed. Antibiotic treatment and therapeutic paracentesis were effective for this condition.
Asunto(s)
Antibacterianos , Cesárea , Infecciones por Salmonella , Salmonella , Humanos , Femenino , Adulto , Cesárea/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Salmonella/aislamiento & purificación , Infecciones por Salmonella/diagnóstico , Infecciones por Salmonella/tratamiento farmacológico , Embarazo , Meropenem/uso terapéutico , Meropenem/administración & dosificación , Ascitis/etiología , Ascitis/microbiología , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico , Complicaciones Posoperatorias/microbiología , Paracentesis/métodosRESUMEN
The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination therapy in carbapenem-resistant Gram-negative infections. The aim of this reverse translational study was to integrate all individual preclinical and clinical pharmacokinetic-pharmacodynamic (PKPD) data from the AIDA trial in a pharmacometric framework to explore whether individualized predictions of bacterial burden were associated with the trial outcomes. The compiled dataset included for each of the 207 patients was (i) information on the infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, and fitness in a murine model), (ii) colistin plasma concentrations and colistin and meropenem dosing history, and (iii) disease scores and demographics. The individual information was integrated into PKPD models, and the predicted change in bacterial count at 24 h for each patient, as well as patient characteristics, was correlated with clinical outcomes using logistic regression. The in vivo fitness was the most important factor for change in bacterial count. A model-predicted growth at 24 h of ≥2-log10 (164/207) correlated positively with clinical failure (adjusted odds ratio, aOR = 2.01). The aOR for one unit increase of other significant predictors were 1.24 for SOFA score, 1.19 for Charlson comorbidity index, and 1.01 for age. This study exemplifies how preclinical and clinical anti-infective PKPD data can be integrated through pharmacodynamic modeling and identify patient- and pathogen-specific factors related to clinical outcomes - an approach that may improve understanding of study outcomes.
Asunto(s)
Acinetobacter baumannii , Antibacterianos , Meropenem , Pruebas de Sensibilidad Microbiana , Humanos , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Meropenem/farmacocinética , Meropenem/administración & dosificación , Meropenem/farmacología , Persona de Mediana Edad , Femenino , Masculino , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Colistina/farmacocinética , Colistina/administración & dosificación , Adulto , Anciano , Animales , Resultado del Tratamiento , Ratones , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Investigación Biomédica Traslacional , Quimioterapia Combinada/métodos , Modelos BiológicosRESUMEN
BACKGROUND: Continuous infusion of meropenem has been proposed to increase target attainment in critically ill patients, although stability might limit its practical use. This study investigated the impact of meropenem degradation and infusion bag changes on the concentration-time profiles and bacterial growth and killing of P. aeruginosa given different continuous-infusion solutions. METHODS: A semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model quantifying meropenem concentrations (CMEM) and bacterial counts of a resistant P. aeruginosa strain (ARU552, MIC = 16 mg/L) over 24 h was used to translate in vitro antibiotic effects to patients with severe infections. Concentration-dependent drug degradation of saline infusion solutions was considered using an additional compartment in the population PK model. CMEM, fT>MIC (time that concentrations exceed the MIC) and total bacterial load (BTOT) after 24 h were simulated for different scenarios (n = 144), considering low- and high-dose regimens (3000/6000 mg/day±loading dose), clinically relevant infusion solutions (20/40/50 mg/mL), different intervals of infusion bag changes (every 8/24 h, q8/24 h), and varied renal function (creatinine clearance 40/80/120 mL/min) and MIC values (8/16 mg/L). RESULTS: Highest deviations between changing infusion bags q8h and q24h were observed for 50 mg/mL solutions and scenarios with CMEM_24h close to the MIC, with differences (Δ) in CMEM_24h up to 4.9 mg/L, ΔfT>MIC≤65.7%, and ΔBTOT_24h≤1.1 log10 CFU/mL, thus affecting conclusions on whether bacteriostasis was reached. CONCLUSIONS: In summary, this study indicated that for continuous infusion of meropenem, eight-hourly infusion bag changes improved PK/PD target attainment and might be beneficial particularly for high meropenem concentrations of saline infusion solutions and for plasma concentrations in close proximity to the MIC.
Asunto(s)
Antibacterianos , Meropenem , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa , Meropenem/farmacocinética , Meropenem/farmacología , Meropenem/administración & dosificación , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Humanos , Infusiones Intravenosas , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Carga Bacteriana/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Estabilidad de MedicamentosRESUMEN
A 43-year-old man was admitted to our department due to fever and headache. The cerebrospinal fluid analysis confirmed bacterial meningitis. Campylobacter species were isolated from blood cultures on the third day of admission. The patient was treated with meropenem (MEPM) and discharged on the 17th day. However, he experienced a recurrence of meningitis and was readmitted on the 68th day, initiating MEPM therapy. Campylobacter fetus was isolated from cerebrospinal fluid cultures on the 74th day. MEPM was continued until the 81st day, followed by one month of minocycline (MINO) therapy. The patient had an uneventful recovery without further recurrence. This case highlights the potential for recurrence of Campylobacter fetus meningitis approximately two months after the resolution of the initial infection. In addition to carbapenem therapy for at least two weeks, the adjunctive administration of MINO may be beneficial.
Asunto(s)
Antibacterianos , Infecciones por Campylobacter , Campylobacter fetus , Meningitis Bacterianas , Meropenem , Minociclina , Recurrencia , Humanos , Masculino , Adulto , Campylobacter fetus/aislamiento & purificación , Infecciones por Campylobacter/tratamiento farmacológico , Infecciones por Campylobacter/complicaciones , Infecciones por Campylobacter/diagnóstico , Infecciones por Campylobacter/microbiología , Meropenem/administración & dosificación , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Bacterianas/microbiología , Meningitis Bacterianas/diagnóstico , Antibacterianos/administración & dosificación , Factores de Tiempo , Minociclina/administración & dosificación , Resultado del Tratamiento , Tienamicinas/administración & dosificación , Quimioterapia CombinadaRESUMEN
BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are one of the most common causes of nosocomial infections and have high mortality rates due to difficulties in treatment. In this study, the in vitro synergistic interactions of the colistin (CT)-meropenem (MEM) combination and patient clinical outcomes were compared in CRAB-infected patients that receive CT-MEM antimicrobial combination therapy. In addition, in vitro synergistic interactions of MEM-ertapenem (ETP), MEM-fosfomycin (FF) and CT-FF antimicrobial combinations were investigated. Finally, the epsilometer (E) test and checkerboard test results were compared and the compatibility of these two tests was evaluated. METHODS: Twenty-one patients were included in the study. Bacterial identification was performed with MALDI-TOF, and antimicrobial susceptibility was assessed with an automated system. Synergy studies were performed using the E test and checkerboard method. RESULTS: For the checkerboard method, the synergy rates for CT-MEM, MEM-FF, MEM-ETP and CT-FF were 100%, 52.3%, 23.8% and 28.5%, respectively. In the E test synergy tests, synergistic effects were detected for two isolates each in the CT-MEM and CT-FF combinations. Microbial eradication was achieved in nine (52.9%) of the 17 patients that received CT-MEM combination therapy. The agreement between the E test and the checkerboard test was 6.5%. CONCLUSIONS: A synergistic effect was found with the checkerboard method for the CT-MEM combination in all isolates in our study, and approximately 70% of the patients benefited from treatment with this combination. In addition, more than half of the isolates showed a synergistic effect for the MEM-FF combination. Combinations of CT-MEM and MEM-FF may be options for the treatment of CRAB infections. However, a comprehensive understanding of the potential of the microorganism to develop resistant mutants under applied exposures, as well as factors that directly affect antimicrobial activity, such as pharmacokinetics/pharmacodynamics, is essential for providing treatment advice. We found a low rate of agreement between the E test method and the checkerboard test method in our study, in contrast to the literature. Comprehensive studies that compare clinical results with methods are needed to determine the ideal synergy test and interpretation method.
Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Carbapenémicos , Colistina , Pruebas de Sensibilidad Microbiana , Acinetobacter baumannii/efectos de los fármacos , Humanos , Colistina/farmacología , Carbapenémicos/farmacología , Masculino , Femenino , Persona de Mediana Edad , Pruebas de Sensibilidad Microbiana/métodos , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Anciano , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Adulto , Sinergismo Farmacológico , Anciano de 80 o más Años , Quimioterapia Combinada/métodos , Meropenem/farmacología , Meropenem/administración & dosificaciónRESUMEN
. The overlap Stevens-Johnson syndrome due to meropenem administration. Clinical case and nursing care. A case of overlap Stevens-Johnson syndrome caused by meropenem administration is described. It is a rare cutaneous reaction due to delayed hypersensitivity to drugs characterised by the destruction and separation of the skin epithelium and mucous membranes, affecting between 10% and 29% of the body surface area. The clinical description of the case and a detailed description of nursing management and interventions based on the available literature are reported.
Asunto(s)
Antibacterianos , Meropenem , Síndrome de Stevens-Johnson , Síndrome de Stevens-Johnson/enfermería , Síndrome de Stevens-Johnson/etiología , Humanos , Meropenem/administración & dosificación , Meropenem/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Femenino , Masculino , Tienamicinas/administración & dosificación , Tienamicinas/efectos adversosRESUMEN
Background and Objectives: The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged infusions over intermittent ones. In our opinion, this can be related to age, which possibly distorts the final data, as older people have age-related characteristics. In our study, we analyzed the ventilatory status, laboratory tests and vital signs of the patient and carried out microbiological cultures. Materials and Methods: This was a prospective single-center case series investigation conducted from June 2022 to June 2023. The objective of this study was to evaluate the effectiveness of continuous infusion in elderly patients with severe infectious complications after orthopedic interventions. The primary endpoints were 28-day survival and the emergence of new multidrug-resistant strains. Secondary endpoints were long-term mortality and length of stay in the ICU. Results: Three patients (median age 65, 100% female) received a continuous infusion of meropenem. Two patients were alive at hospital discharge, and one patient died on the 105th day of hospitalization. Multi-resistant bacteria were observed in one patient. Conclusions: The use of a continuous meropenem infusion in the complex treatment of purulent-septic complications in elderly patients with periprosthetic infection and anemia probably led to clinical improvement in these case reports. However, the emergence of new pan-resistant strains and overall mortality using this infusion technique remains unclear. Further, high-quality RCTs for the elderly are needed.
Asunto(s)
Anemia , Antibacterianos , Meropenem , Humanos , Meropenem/administración & dosificación , Meropenem/uso terapéutico , Anciano , Femenino , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Estudios Prospectivos , Masculino , Anemia/tratamiento farmacológico , Infusiones Intravenosas , Persona de Mediana Edad , Anciano de 80 o más Años , Sepsis/tratamiento farmacológicoRESUMEN
This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.
Asunto(s)
Antibacterianos , Meropenem , Pruebas de Sensibilidad Microbiana , Choque Séptico , Humanos , Meropenem/farmacocinética , Meropenem/administración & dosificación , Meropenem/uso terapéutico , Choque Séptico/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Adulto , Perforación Intestinal , Anciano de 80 o más AñosRESUMEN
According to the literature, acute otitis media is complicated by mastoiditis in 0.15-1% of cases. In turn, mastoiditis can be complicated by meningitis, encephalitis, abscess of temporal lobe of brain and cerebellum, epidural and subdural abscesses, facial nerve paresis, labyrinthitis, phlegmon of soft tissues of neck, as well as subperiosteal abscess, which makes 7% in the structure of mastoiditis complications. Nowadays, when doctors have a wide range of antibacterial preparations at their disposal, a complicated course of acute otitis media and further mastoiditis is caused both by an aggressive atypical infectious agent and immunocompromised status of a patient. The article deals with a clinical case of a prolonged course of acute otitis media complicated by mastoiditis and subperiosteal abscess against the background of outpatient courses of antibacterial therapy. The examination revealed an atypical pathogen of otitis media Pseudomonas aeruginosa and HIV-positive status of the patient, previously unknown. Timely surgical intervention and the right combination of antibacterial drugs, meropenem and ciprofloxacin, prevented the development of intracranial and septic complications, despite the presence of multiple foci of bone destruction of the mastoid process and temporal bone pyramid, bordering the middle fossa and sigmoid sinus, according to multispiral head computed tomography. As a part of additional examination in the Center for AIDS and Infectious Diseases Prevention and Control, the patient was diagnosed with HIV infection, clinical stage 4C, progressing phase on the background of absence of antiretroviral therapy, and the necessary amount of treatment was prescribed.
Asunto(s)
Antibacterianos , Mastoiditis , Otitis Media Supurativa , Adulto , Humanos , Masculino , Enfermedad Aguda , Antibacterianos/uso terapéutico , Infecciones por VIH/complicaciones , Mastoiditis/etiología , Mastoiditis/diagnóstico , Meropenem/administración & dosificación , Meropenem/uso terapéutico , Otitis Media Supurativa/diagnóstico , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones por Pseudomonas/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low. METHODS: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30-day all-cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90- and 180-day all-cause mortality and 180-day health-related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow-up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%-points) and response-adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios. CONCLUSIONS: EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice.
Asunto(s)
Antibacterianos , Meropenem , Combinación Piperacilina y Tazobactam , Sepsis , Humanos , Meropenem/uso terapéutico , Meropenem/administración & dosificación , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Combinación Piperacilina y Tazobactam/uso terapéutico , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Adulto , Enfermedad Crítica , MasculinoRESUMEN
OBJECTIVE: The timing and dosing of antimicrobial therapy are key in the treatment of pneumonia in critically ill patients. It is uncertain whether the presence of lung inflammation and injury affects tissue penetration of intravenously administered antimicrobial drugs. The effects of lung inflammation and injury on tissue penetration of two antimicrobial drugs commonly used for pneumonia were determined in an established model of unilateral lung injury. METHODS: Unilateral lung injury was induced in the left lung of 13 healthy pigs through cyclic rinsing; the right healthy lung served as control. Infusions of meropenem and vancomycin were administered and concentrations of these drugs in lung tissue, blood, and epithelial lining fluid (ELF) were compared over a period of 6 h. RESULTS: Median vancomycin lung tissue concentrations and penetration ratio were higher in inflamed and injured lungs compared with uninflamed and uninjured lungs (AUC0-6h: P = 0.003 and AUCdialysate/AUCplasma ratio: P = 0.003), resulting in higher AUC0-24/MIC. Median meropenem lung tissue concentrations and penetration ratio in inflamed and injured lungs did not differ from that in uninflamed and uninjured lungs (AUC0-6: P = 0.094 and AUCdialysate/AUCplasma ratio: P = 0.173). The penetration ratio for both vancomycin and meropenem into ELF was similar in injured and uninjured lungs. CONCLUSION: Vancomycin penetration into lung tissue is enhanced by acute inflammation and injury, a phenomenon barely evident with meropenem. Therefore, inflammation in lung tissue influences the penetration into interstitial lung tissue, depending on the chosen antimicrobial drug. Measurement of ELF levels alone might not identify the impact of inflammation and injury.
Asunto(s)
Antibacterianos , Modelos Animales de Enfermedad , Lesión Pulmonar , Pulmón , Meropenem , Vancomicina , Animales , Meropenem/farmacocinética , Meropenem/administración & dosificación , Vancomicina/farmacocinética , Vancomicina/administración & dosificación , Porcinos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Pulmón/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Neumonía/tratamiento farmacológico , Femenino , Pruebas de Sensibilidad MicrobianaRESUMEN
Piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) and vancomycin (VAN) are commonly used in combination for sepsis. Studies have shown an increased risk of acute kidney injury (AKI) with TZP and VAN compared to FEP or MEM. VAN guidelines recommend area under the curve (AUC) monitoring over trough (Tr) to minimize the risk of AKI. We investigated the association of AKI and MAKE-30 with the two VAN monitoring strategies when used in combination with TZP or FEP/MEM. Adult patients between 2015 and 2019 with VAN > 72 hours were included. Patients with AKI prior to or within 48 hours of VAN or baseline CrCl of ≤30 mL/min were excluded. Four cohorts were defined: FEP/MEM/Tr, FEP/MEM/AUC, TZP/Tr, and TZP/AUC. A Cox Proportional Hazard Model was used to model AKI as a function of the incidence rate of at-risk days, testing monitoring strategy as a treatment effect modification. Multivariable logistic regression was used to model MAKE-30. Overall incidence of AKI was 18.6%; FEP/MEM/Tr = 115 (14.6%), FEP/MEM/AUC = 52 (14.9%), TZP/Tr = 189 (26%), and TZP/AUC = 96 (17.1%) (P < 0.001). Both drug group [(TZP; P = 0.0085)] and monitoring strategy [(Tr; P = 0.0007)] were highly associated with the development of AKI; however, the effect was not modified with interaction term [(TZP*Tr); 0.085)]. The odds of developing MAKE-30 were not different between any group and FEP/MEM/AUC. The effect of VAN/TZP on the development of AKI was not modified by the VAN monitoring strategy (AUC vs trough). MAKE-30 outcomes were not different among the four cohorts.
Asunto(s)
Lesión Renal Aguda , Antibacterianos , Cefepima , Meropenem , Combinación Piperacilina y Tazobactam , Vancomicina , Humanos , Vancomicina/efectos adversos , Vancomicina/administración & dosificación , Vancomicina/uso terapéutico , Meropenem/administración & dosificación , Meropenem/uso terapéutico , Meropenem/efectos adversos , Lesión Renal Aguda/inducido químicamente , Cefepima/administración & dosificación , Cefepima/uso terapéutico , Cefepima/efectos adversos , Combinación Piperacilina y Tazobactam/efectos adversos , Combinación Piperacilina y Tazobactam/administración & dosificación , Combinación Piperacilina y Tazobactam/uso terapéutico , Masculino , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Femenino , Persona de Mediana Edad , Anciano , Área Bajo la Curva , Quimioterapia Combinada , Estudios Retrospectivos , Sepsis/tratamiento farmacológicoRESUMEN
A 76-year-old Malay female presented with 2 days history of fever and vomiting. She was found to have Escherichia coli and Klebsiella pneumoniae bacteraemia with no clear intra-abdominal cause on the initial computed tomography of the abdomen and pelvis (CTAP). She clinically improved with 2 weeks duration of intravenous meropenem. She subsequently developed septic shock and a repeated CTAP demonstrated increased hepatic parenchymal density with extensive parenchymal calcifications. Curvilinear calcifications were seen in the paraspinal and pelvic musculature.
Asunto(s)
Calcinosis , Humanos , Femenino , Anciano , Calcinosis/diagnóstico por imagen , Sepsis/microbiología , Tomografía Computarizada por Rayos X , Hepatopatías/diagnóstico por imagen , Klebsiella pneumoniae/aislamiento & purificación , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/diagnóstico , Infecciones por Escherichia coli/tratamiento farmacológico , Enfermedades Musculares/diagnóstico por imagen , Antibacterianos/uso terapéutico , Meropenem/uso terapéutico , Meropenem/administración & dosificaciónRESUMEN
OBJECTIVE: This study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co-administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA. METHODS: We retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co-administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co-administerd VPA and other broad-spectrum antibiotics were allocated to the control group. RESULTS: The exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co-administration (24.6 ± 4.3 µg/mL) compared with that before co-administration (88.8 ± 13.6 µg/mL, p < 0.0001), and it was partly recovered with the termination of co-administration (39.8 ± 13.2 µg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before-during and before-after (p = 0.074 and 0.153, respectively). Seizure duration during VPA-MEPM co-administration was not significantly different from that before co-administration (p = 0.291). CONCLUSIONS: In this study, the reduced plasma concentration of VPA induced by the co-administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020.
Asunto(s)
Anticonvulsivantes , Epilepsia , Meropenem , Ácido Valproico , Humanos , Ácido Valproico/sangre , Ácido Valproico/uso terapéutico , Ácido Valproico/administración & dosificación , Anticonvulsivantes/sangre , Anticonvulsivantes/uso terapéutico , Meropenem/sangre , Meropenem/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Anciano , Epilepsia/tratamiento farmacológico , Epilepsia/sangre , Interacciones Farmacológicas , Antibacterianos/sangre , Antibacterianos/administración & dosificación , Resultado del TratamientoRESUMEN
OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.
Asunto(s)
Antibacterianos , Compuestos de Azabiciclo , Proteínas Bacterianas , Ceftazidima , Modelos Animales de Enfermedad , Combinación de Medicamentos , Sinergismo Farmacológico , Infecciones por Klebsiella , Klebsiella pneumoniae , Meropenem , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , Animales , Ceftazidima/farmacología , Ceftazidima/uso terapéutico , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Meropenem/farmacología , Meropenem/administración & dosificación , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ratones , beta-Lactamasas/genética , Proteínas Bacterianas/genética , Femenino , Secuenciación Completa del Genoma , Quimioterapia Combinada , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/genéticaRESUMEN
OBJECTIVE: A case of post-neurosurgical ventriculitis caused by a KPC-producing Klebsiella pneumoniae (KPC-Kp) with a ceftazidime/avibactam-resistant, meropenem-susceptible phenotype is reported. METHODS AND RESULTS: The patient had a concomitant bloodstream infection with a wild-type KPC-Kp with a ceftazidime/avibactam-susceptible, meropenem-resistant phenotype. Prolonged treatment with intravenous fosfomycin and meropenem/vaborbactam achieved clinical success. Therapeutic drug monitoring performed during the first days of treatment showed for the first time that vaborbactam efficiently penetrates cerebrospinal fluid. In contrast, meropenem was undetectable in cerebrospinal fluid at each sampling, suggesting that additional doses of meropenem may be required to appropriately prescribe meropenem/vaborbactam for central nervous system infections. Plasma and cerebrospinal fluid levels of fosfomycin were adequate, confirming the potential of this agent possibly even in the fight against multidrug-resistant organisms. CONCLUSIONS: This case highlights the need for therapeutic drug monitoring as a crucial tool for optimizing treatment in complicated cases where the pharmacokinetic behaviour of antibiotics is difficult to predict.
Asunto(s)
Antibacterianos , Bacteriemia , Ácidos Borónicos , Ventriculitis Cerebral , Fosfomicina , Infecciones por Klebsiella , Klebsiella pneumoniae , Meropenem , Humanos , Fosfomicina/uso terapéutico , Fosfomicina/administración & dosificación , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/enzimología , Meropenem/administración & dosificación , Meropenem/uso terapéutico , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Ventriculitis Cerebral/tratamiento farmacológico , Ventriculitis Cerebral/microbiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Ácidos Borónicos/administración & dosificación , Pruebas de Sensibilidad Microbiana , Masculino , beta-Lactamasas/metabolismo , Farmacorresistencia Bacteriana Múltiple , Persona de Mediana Edad , Combinación de Medicamentos , Femenino , Procedimientos Neuroquirúrgicos , Resultado del Tratamiento , Compuestos Heterocíclicos con 1 AnilloRESUMEN
OBJECTIVES: The aim was to assess the impact of the SARS-CoV-2 pandemic on the prevalence, relative incidence (RI), incidence density (ID), ratio of rate incidence (RRI), rate of incidence density (RID), and relative risks (RR) of healthcare-onset Clostridioides difficile infection (HO-CDI) as well as its correlation with the antibiotic consumption. METHODS: Demographic and analytical data of adult patients exhibiting diarrhoea and testing positive for C. difficile were systematically collected from a tertiary care hospital in Madrid (Spain). The periods analysed included: prepandemic (P0), first pandemic-year (P1), and second pandemic-year (P2). We compared global prevalence, RI of HO-CDI per 1,000-admissions, ID of HO-CDI per 10,000-patients-days, RRI, RID, and RR. Antibiotic consumption was obtained by number of defined daily dose per 100 patient-days. RESULTS: In P0, the prevalence of HO-CDI was 7.4% (IC95%: 6.2-8.7); in P1, it increased to 8.7% (IC95%: 7.4-10.1) (p = 0.2), and in P2, it continued to increase to 9.2% (IC95%: 8-10.6) (p < 0.05). During P1, the RRI was 1.5 and RID was 1.4. However, during P2 there was an increase in RRI to 1.6 and RID to 1.6. The RR also reflected the increase in HO-CDI: at P1, the probability of developing HO-CDI was 1.5 times (IC95%: 1.2-1.9) higher than P0, while at P2, this probability increased to 1.6 times (IC95%: 1.3-2.1). There was an increase in prevalence, RI, ID, RR, RRI, and RID during the two postpandemic periods respect to the prepandemic period. During P2, this increase was greater than the P1. Meropenem showed a statistically significant difference increased consumption (p < 0.05) during the pandemic period. Oral vancomycin HO-CDI treatment showed an increase during the period of study (p > 0.05). CONCLUSIONS: Implementation of infection control measures during the SARS-CoV-2 pandemic did not appear to alleviate the burden of HO-CDI. The escalation in HO-CDI cases did not exhibit a correlation with overall antibiotic consumption, except for meropenem.
Asunto(s)
COVID-19 , Clostridioides difficile , Infecciones por Clostridium , Infección Hospitalaria , Centros de Atención Terciaria , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/microbiología , Humanos , COVID-19/epidemiología , Diarrea/epidemiología , Vancomicina/administración & dosificación , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , España/epidemiología , Estudios Retrospectivos , Incidencia , Brotes de Enfermedades , Prevalencia , Antibacterianos/administración & dosificación , Riesgo , Pandemias/estadística & datos numéricos , Control de Infecciones/estadística & datos numéricos , Meropenem/administración & dosificación , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
PURPOSE: To date, there are three published guidelines discussing management of infected pancreatic necrosis (IPN) with conflicting recommendations. Specifically, The World Society of Emergency Surgery lists piperacillin-tazobactam as a treatment option in addition to meropenem and ciprofloxacin plus metronidazole. Piperacillin-tazobactam may serve as an effective carbapenem-sparing alternative. Although previous studies shed light on antimicrobial penetration data, there is a lack of clinical data comparing piperacillin-tazobactam to meropenem. The purpose of this study is to compare the efficacy of meropenem and piperacillin-tazobactam for the treatment of IPN. METHODS: This was a multicenter, retrospective cohort study conducted across three institutions. Patients with IPN who received either meropenem or piperacillin-tazobactam from January 2015 to December 2020 were included. The primary composite outcome was the incidence of 90-day clinical failure, which encompassed 90-day all-cause mortality and 90-day intra-abdominal infection recurrence. Secondary outcomes included length of hospital stay, antimicrobial duration of therapy, and the need for surgical intervention. RESULTS: We identified 229 patients with IPN that received either meropenem or piperacillin-tazobactam during hospital admission. After screening, 63 patients were included in the study. Incidence of 90-day clinical failure was observed in 33 % of the meropenem group and 50 % in the piperacillin-tazobactam group (OR, 1.98; 95 % CI 0.57 to 7.01, p = 0.259). The meropenem group had a lower incidence of 90-day infection recurrence in the piperacillin-tazobactam group (56 % vs 29 %, p = 0.047). CONCLUSIONS: Piperacillin-tazobactam may be an efficacious carbapenem-sparing treatment alternative for infected pancreatic necrosis.
Asunto(s)
Antibacterianos , Meropenem , Combinación Piperacilina y Tazobactam , Humanos , Meropenem/uso terapéutico , Meropenem/administración & dosificación , Combinación Piperacilina y Tazobactam/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Anciano , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Adulto , Resultado del TratamientoRESUMEN
PURPOSE: Intravenous push antibiotics can serve as an alternative to intravenous piggyback antibiotics while providing the same pharmacodynamics and adverse effect profile, easing shortage pressures and decreasing order to administration time, as well as representing a potential cost savings. The purpose of this study was to determine whether intravenous push antibiotics could decrease the time from an order to the start of administration compared to piggyback antibiotics in emergency departments. This study also measured the cost savings of antibiotic preparation and administration and assessed nursing satisfaction when using intravenous push antibiotics. METHODS: Sample instances of use of intravenous push and piggyback antibiotics were identified. Patients were included if they were 18 years of age or older and received at least a single dose of intravenous push or piggyback ceftriaxone, cefepime, cefazolin, or meropenem in one of the institution's emergency departments. The primary outcome of the study was to compare the time from the order to the start of administration of intravenous push vs piggyback antibiotics. The secondary outcome was to compare the cost of antibiotic preparation for the 2 methods. RESULTS: The intravenous push and piggyback groups each had 43 patients. The time from the order to the start of administration decreased from 74 (interquartile range, 29-114) minutes in the piggyback group to 31 (interquartile range, 21-52) minutes in the push group (P = 0.003). When the estimated monthly cost savings for ceftriaxone, cefepime, and meropenem were added together, across the emergency departments, an estimated $227,930.88 is saved per year when using intravenous push antibiotics. CONCLUSION: Intravenous push antibiotics decrease the time from ordering to the start of administration and result in significant cost savings.
Asunto(s)
Antibacterianos , Ahorro de Costo , Servicio de Urgencia en Hospital , Humanos , Antibacterianos/administración & dosificación , Antibacterianos/economía , Servicio de Urgencia en Hospital/economía , Femenino , Masculino , Persona de Mediana Edad , Infusiones Intravenosas , Anciano , Administración Intravenosa , Adulto , Ceftriaxona/administración & dosificación , Ceftriaxona/economía , Meropenem/administración & dosificación , Meropenem/economía , Estudios Retrospectivos , Cefepima/administración & dosificación , Factores de TiempoRESUMEN
BACKGROUND: Lysins (cell wall hydrolases) targeting gram-negative organisms require engineering to permeabilize the outer membrane and access subjacent peptidoglycan to facilitate killing. In the current study, the potential clinical utility for the engineered lysin CF-370 was examined in vitro and in vivo against gram-negative pathogens important in human infections. METHODS: Minimum inhibitory concentration (MICs) and bactericidal activity were determined using standard methods. An in vivo proof-of-concept efficacy study was conducted using a rabbit acute pneumonia model caused by Pseudomonas aeruginosa. RESULTS: CF-370 exhibited potent antimicrobial activity, with MIC50/90 values (in µg/mL) for: P aeruginosa, 1/2; Acinetobacter baumannii, 1/1; Escherichia coli, 0.25/1; Klebsiella pneumoniae, 2/4; Enterobacter cloacae 1/4; and Stenotrophomonas maltophilia 2/8. CF-370 furthermore demonstrated bactericidal activity, activity in serum, a low propensity for resistance, anti-biofilm activity, and synergy with antibiotics. In the pneumonia model, CF-370 alone decreased bacterial densities in lungs, kidneys, and spleen versus vehicle control, and demonstrated significantly increased efficacy when combined with meropenem (vs either agent alone). CONCLUSIONS: CF-370 is the first engineered lysin described with potent broad-spectrum in vitro activity against multiple clinically relevant gram-negative pathogens, as well as potent in vivo efficacy in an animal model of severe invasive multisystem infection.