Rate Of Therapeutic Failure Research Articles

Planning and diagnostic nursing strategy in the clinical management of the patient with hyperthroidism

Hyperthyroidism is a common disease that affects 0.8% of the population in Europe. It occurs when the thyroid gland produces more thyroid hormones than your body needs. There are several types of treatment, such as antithyroid drugs, treatment with radioactive iodine (131I) and finally surgery, in addition to these treatments, reference is made to a good hygienic-dietary orientation. Objective: to assess from the nursing field the safest and most effective type of hyperthyroidism treatment, including the risk factors to take into account when carrying out these. Methodology: systematic searches were carried out in bibliographic sources of trials and articles published between 2015 and 2021. Including studies that contained data on risk factors for hyperthyroidism. Results: of 426 related articles found, 13 met the inclusion criteria. Total thyroidectomy surgery induced a 26% therapeutic failure rate and 95% radioactive iodine treatment compared to the 19.1% therapeutic failure in antithyroid drug treatment. Conclusion: Despite the verification of the efficacy of all existing hyperthyroidism treatments, antithyroid drugs have greater efficacy and safety than the rest of the treatments studied, in relation to the time and rate of remission. On the other hand, risk factors such as tobacco and female sex are evidenced, which are negative factors when carrying out treatment for hyperthyroidism.

Five-Year Long-Term Follow-Up of Selective Laser Trabeculoplasty in Open-Angle Glaucoma.

Selective laser trabeculoplasty (SLT) is known as a safe laser therapy for an effective reduction in intraocular pressure (IOP). The aim of this study was to examine the therapeutic success of SLT in open-angle glaucoma (OAG) patients with a long-term follow-up of 5 years. Forty-six eyes of forty OAG patients, some with previous intraocular surgery, underwent SLT (24 males, 16 females). Therapeutic success was categorized as: category (I) - IOP reduction ≤ 21 mmHg and > 20% compared to baseline IOP with additional glaucoma medication; category (II) - IOP reduction ≤ 18 mmHg and > 30% compared to baseline IOP with additional glaucoma medication; category (III) - IOP reduction ≤ 18 mmHg without any additional glaucoma medication at all follow-ups. Therapeutic failure was defined as the necessity of any further glaucoma surgery (IV). (1) SLT was well tolerated in all eyes, and no severe side effects or complications were recorded. (2) After 1-year follow-up, therapeutic success was 27% (I), 30% (II), and 3% (III). The therapeutic failure rate was 40% (IV). (3) After 2years follow-up, therapeutic success was 7% (I), 10% (II), and 0% (III). The therapeutic failure rate was 83% (IV). (4) After 3years follow-up, the therapeutic failure rate increased up to 100% (IV). SLT seemed to be effective in lowering IOP in the first year in the present cohort, however, the long-term effect is low and additional local therapy or surgical interventions are necessary.

Prevention of Stress-Induced Depressive-like Behavior by Saffron Extract Is Associated with Modulation of Kynurenine Pathway and Monoamine Neurotransmission.

Depressive disorders are a major public health concern. Despite currently available treatment options, their prevalence steadily increases, and a high rate of therapeutic failure is often reported, together with important antidepressant-related side effects. This highlights the need to improve existing therapeutic strategies, including by using nutritional interventions. In that context, saffron recently received particular attention for its beneficial effects on mood, although the underlying mechanisms are poorly understood. This study investigated in mice the impact of a saffron extract (Safr’Inside™; 6.25 mg/kg, per os) on acute restraint stress (ARS)-induced depressive-like behavior and related neurobiological alterations, by focusing on hypothalamic–pituitary–adrenal axis, inflammation-related metabolic pathways, and monoaminergic systems, all known to be altered by stress and involved in depressive disorder pathophysiology. When given before stress onset, Safr’Inside administration attenuated ARS-induced depressive-like behavior in the forced swim test. Importantly, it concomitantly reversed several stress-induced monoamine dysregulations and modulated the expression of key enzymes of the kynurenine pathway, likely reducing kynurenine-related neurotoxicity. These results show that saffron pretreatment prevents the development of stress-induced depressive symptoms and improves our understanding about the underlying mechanisms, which is a central issue to validate the therapeutic relevance of nutritional interventions with saffron in depressed patients.

Development of CMV-CD19 bi-specific CAR T cells with post-infusion in vivo boost using an anti-CMV vaccine.

Adoptive transfer of in vitro expanded, chimeric antigen receptor (CAR)-redirected CD19-specific T cells can induce dramatic disease regression in patients with leukemia and lymphomas. However, the full potential of this emerging modality is hampered in some cancer settings by a significant rate of therapeutic failure arising from the attenuated engraftment and persistence of CAR-redirected T cells, and tumor relapse following adoptive transfer. Here, we discuss an advanced strategy that facilitates post-infusion in vivo boosting of CAR T cells via CMV vaccination, to mediate durable remission of B cell malignancies by engrafting a CAR molecule onto a CMV-specific T cell. We also discuss a feasible and unique platform for the generation of the CMV-CD19CAR T cells for clinical application. This new approach would overcome multiple challenges in current CAR T cell technology including: short T cell persistence, limited duration of response, and inability to re-stimulate T cells after relapse or persistent disease.

Nutritional status of pediatric patients living with human immunodeficiency virus in Bogotá, Colombia

Background: Undernutrition is frequent among children living with HIV in developing countries. An interaction between malnutrition and HIV pediatric infection remains incompletely characterized in Colombia. Methodology: Retrospective longitudinal study, descriptive in nature, in 28 patients with a diagnosis of HIV infection, less than 18 years of age and receiving antiretroviral therapy. Variables were retrieved from clinical records at start of antiretroviral therapy and after 12 months. Statistical analysis was exploratory. Results: 4 out of 28 patients were stunted (14,3%; 95%CI: 1,3 – 27,2), 2 out of 7 patients were wasted (28,6%; 95%CI: 0 – 62), 5 out of 17 patients were underweight (27,8%; 95%CI: 7,1 – 48,5) and 4 out of 28 patients had thinness (29,6%; 95%CI: 12,4 – 46,8). No clinically relevant anthropometric change was detected during follow-up. Anemia prevalence was 52% and 82% of patients had some degree of dyslipidemia. Both viral load (p=0,001) and CD4 count (p=0,01), significantly increased and the proportion of patients with therapeutic failure remained invariable during follow-up. Conclusion: Malnutrition is frequent and its prevalence might have decreased. HIV program improved medical control of the disease, with stable therapeutic failure rates that were comparable with previous reports. Nonetheless, anemia and dyslipidemia remain to be a paramount therapeutic challenge.

A High Rate of Recurrent Vulvovaginal Candidiasis and Therapeutic Failure of Azole Derivatives Among Iranian Women.

Recurrent vulvovaginal candidiasis (RVVC) is one of the most prevalent fungal infections in humans, especially in developing countries; however, it is underestimated and regarded as an easy-to-treat condition. RVVC may be caused by dysbiosis of the microbiome and other host-, pathogen-, and antifungal drug-related factors. Although multiple studies on host-related factors affecting the outcome have been conducted, such studies on Candida-derived factors and their association with RVVC are lacking. Thus, fluconazole-tolerant (FLZT) isolates may cause fluconazole therapeutic failure (FTF), but this concept has not been assessed in the context of Candida-associated vaginitis. Iran is among the countries with the highest burden of RVVC; however, comprehensive studies detailing the clinical and microbiological features of this complication are scarce. Therefore, we conducted a 1-year prospective study with the aim to determine the RVVC burden among women referred to a gynecology hospital in Tehran, the association of the previous exposure to clotrimazole and fluconazole with the emergence of FLZT and fluconazole-resistant (FLZR) Candida isolates, and the relevance of these phenotypes to FTF. The results indicated that about 53% of the patients (43/81) experienced RVVC. Candida albicans and C. glabrata constituted approximately 90% of the yeast isolates (72 patients). Except for one FLZT C. tropicalis isolate, FLZR and FLZT phenotypes were detected exclusively in patients with RVVC; among them, 27.9% (12/43) harbored FLZR strains. C. albicans constituted 81.2% of FLZR (13/16) and 100% of the FLZT (13/13) isolates, respectively, and both phenotypes were likely responsible for FTF, which was also observed among patients with RVVC infected with fluconazole-susceptible isolates. Thus, FTF could be due to host-, drug-, and pathogen-related characteristics. Our study indicates that FLZT and FLZR isolates may arise following the exposure to over-the-counter (OTC) topical azole (clotrimazole) and that both phenotypes can cause FTF. Therefore, the widespread use of OTC azoles can influence fluconazole therapeutic success, highlighting the necessity of controlling the use of weak topical antifungals among Iranian women.

Clonal Candidemia Outbreak by Candida parapsilosis Carrying Y132F in Turkey: Evolution of a Persisting Challenge.

As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019–2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019–2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.

Allergy to penicillin and betalactam antibiotics.

ABSTRACTBetalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to betalactam is to discontinue exposure to the drug, and the only specific treatment is desensitization, which has very precise indications. The misdiagnosis of penicillin allergy affects the health system, since the “penicillin allergy” label is associated with increased bacterial resistance, higher rate of therapeutic failure, prolonged hospitalizations, readmissions, and increased costs. Thus, it is essential to develop strategies to assist the prescription of antibiotics in patients identified with a label of “betalactam allergy” at hospitals, and to enhance education of patients and their caregivers, as well as of non-specialist physicians.

Antimicrobial Dosing in Specific Populations and Novel Clinical Methodologies: Obesity.

Obesity and its related comorbidities can negatively influence the outcomes of certain infectious diseases. Specific dosing recommendations are often lacking in the product label for patients with obesity that leads to unclear guidance in practice. Higher rates of therapeutic failure have been reported with some fixed dose antibiotics and pragmatic approaches to dose modification are limited for orally administered agents. For i.v. antimicrobials dosed on weight, alternate body size descriptors (ABSDs) have been used to reduce the risk of overdosing. These ABSDs are mathematical transformations of height and weight that represent fat-free weight and follow the same principles as body surface area (BSA)-based dosing of cancer chemotherapy. However, ABSDs are rarely studied in pivotal phase III studies and so can risk the underdosing of antimicrobials in patients with obesity when incorrectly applied in the real-world setting. Specific case examples are presented to highlight these risks. Although general principles may be considered by clinicians, a universal approach to dose modification in obesity is unlikely. Studies that can better distinguish human body phenotypes may help reduce our reliance on height and weight to define dosing. Simple and complex technologies exist to quantify individual body composition that could improve upon our current approach. Early evidence suggests that body composition parameters repurposed from medical imaging data may improve upon height and weight as covariates of drug clearance and distribution. Clinical trials that can integrate human body phenotyping may help us identify new approaches to optimal dose selection of antimicrobials in patients with obesity.

The evolution of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio during polychemotherapy in head and neck cancers

The identification of prognostic and predictive biomarkers in oncological pathology is a desideratum of translational research in cancer. The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) were considered sug­ges­tive to characterize both cell-mediated immune sta­tus and inflammation in cancer, thus being potential bio­mar­kers. Due to the high rate of therapeutic failure even in the case of a treatment with curative potential, head and neck cancers are a priority in the research of po­ten­tial biomarkers that allow a stratification of risk groups in order to adapt the therapy. The aim of the study is the dynamic evaluation of NLR and nadir PLR and du­ring chemotherapy cycles for patients with multimodal, nonsurgically treated head and neck cancers. The mean NLR and PLR values vary during treatment, but the mean nadir value is not significantly different from the mean NLR and PLR values before the last cycle of chemotherapy. If there is solid evidence regarding the role of NLR nadir as a biomarker, the evaluation of NLR and PLR dynamics re­quires further research to confirm the possibility of being validated as a prognostic or predictive biomarker of re­sponse to chemotherapy and radiotherapy in head and neck squamous cell carcinoma.

Clinical and microbiological features of candiduria in critically ill adult patients in Shiraz, Iran (2016-2018): deviations from international guidelines and fluconazole therapeutic failure.

Candiduria is an underestimated clinical presentation among critically ill patients and detailed data are scarce in this regard. Given the high rate of fluconazole therapeutic failure and development of candidemia in some cases, the mistreatment of candiduria should not be overlooked by clinicians.

Comparative Analysis of Dacryo Cysto-Rhinostomy: External Versus Endoscopic

Dacryocystorhinostomy (DCR) is a surgical procedure that restores communication between the tear sac and the adjacent nasal cavity. Our work consists of a comparative study of the results of external dacryocystorhinostomy (EX-DCR) versus endoscopic endonasal dacryocystorhinostomy (EN-DCR), whose rate of therapeutic failure by endoscopic route estimated at 20% against only 7% in the case of external surgery.

New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: Clinical, Parasitological, and Serological Assessment after Three Years of Follow-Up.

In a pilot study, we showed that the intermittent administration of benznidazole in chronic Chagas disease patients resulted in a low rate of treatment suspension and therapeutic failure, as assessed by quantitative PCR (qPCR) at the end of treatment. Here, a 3-year posttreatment follow-up study of the same cohort of patients is presented. The treatment scheme consisted of 12 doses of benznidazole at 5 mg/kg of body weight/day in two daily doses every 5 days. Parasite load, Trypanosoma cruzi-specific antibodies, and serum chemokine levels were measured prior to treatment and after a median follow-up of 36 months posttreatment by DNA minicircle kinetoplastid and nuclear DNA satellite sequence qPCR methods, conventional serological techniques, a Luminex-based assay with recombinant T. cruzi proteins, and a cytometric bead array. At the end of follow-up, 14 of 17 (82%) patients had negative qPCR findings, whereas three of 17 (18%) had detectable nonquantifiable findings by at least one of the qPCR techniques. A decline in parasite-specific antibodies at 12 months posttreatment was confirmed by conventional serological tests and the Luminex assays. Monocyte chemoattractant protein 1 levels increased after treatment, whereas monokine induced by gamma interferon levels decreased. New posttreatment electrocardiographic abnormalities were observed in only one patient who had cardiomyopathy prior to treatment. Together, these data strengthen our previous findings by showing that the intermittent administration of benznidazole results in a low rate of treatment suspension, with treatment efficacy comparable to that of a daily dose of 5 mg/kg for 60 days.

Epidemiology of candidemia in Shiraz, southern Iran: A prospective multicenter study (2016-2018).

Systematic candidemia studies, especially in southern Iran, are scarce. In the current prospective study, we investigated candidemia in three major healthcare centers of Shiraz, the largest city in southern Iran. Yeast isolates from blood and other sterile body fluids were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method. Clinical data were retrieved from patients' medical records. In total, 113 yeast isolates were recovered from 109 patients, over 60% of whom received fluconazole. Antifungal drugs were prescribed without considering species identification or AFST. The all-cause mortality rate was 28%. Almost 30% of the patients were from intensive care units (ICUs). Candida albicans (56/113; 49.5%) was the most prevalent species followed by C. glabrata (26/113; 23%), C. parapsilosis (13/113; 11.5%), C. tropicalis (7/113; 6.2%), and C. dubliniensis (5/113; 4.4%). Only five isolates showed antifungal resistance or decreased susceptibility to fluconazole: one C. orthopsilosis isolate from an azole-naïve patient and two C. glabrata, one C. albicans, and one C. dubliniensis isolates from patients treated with azoles, who developed therapeutic failure against azoles later. Our results revealed a low level of antifungal resistance but a notable rate of azole therapeutic failure among patients with candidemia due to non-albicans Candida species, which threaten the efficacy of fluconazole, the most widely used antifungal in southern regions of Iran. Candidemia studies should not be confined to ICUs and treatment should be administered based on species identification and AFST results.

Impact of duration of antibiotic therapy in central venous catheter-related bloodstream infection due to Gram-negative bacilli.

A progressive increase in the incidence of catheter-related bloodstream infection (CRBSI) due to Gram-negative bacilli (GNB) has been reported. Current guidelines recommend antibiotic treatment for at least 7-14 days, although the supporting evidence is limited. We performed a retrospective single-centre study including all patients with a definite diagnosis of GNB CRBSI from January 2012 to October 2018 in which the central venous catheter (CVC) was removed. The occurrence of therapeutic failure [clinical failure (persistence of symptoms and laboratory signs of infection), microbiological failure (persistent bacteraemia or relapse) and/or all-cause 30 day mortality] was compared between episodes receiving short [≤7 days (SC)] or long courses [>7 days (LC)] of appropriate antibiotic therapy following CVC removal. We included 54 GNB CRBSI episodes with an overall rate of therapeutic failure of 27.8% (15/54). Episodes receiving SC therapy were more frequently due to MDR GNB [60.9% (14/23) versus 34.5% (10/29); P = 0.058] and had higher Pitt scores [median (IQR) 1 (0-4) versus 0 (0-2); P = 0.086]. There were no significant differences in the rate of therapeutic failure between episodes treated with SC or LC therapy [30.4% (7/23) versus 27.6% (8/29); OR 1.15; 95% CI 0.34-3.83; P = 0.822]. The use of SCs was not associated with increased odds of therapeutic failure in any of the exploratory models performed. The administration of appropriate antibiotic therapy for ≤7 days may be as safe and effective as longer courses in episodes of GNB CRBSI once the CVC has been removed.

Long-term obstructive sleep apnea therapy: a 10-year follow-up of mandibular advancement device and continuous positive airway pressure

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder, commonly managed by either continuous positive airway pressure (CPAP) or a mandibular advancement device (MAD). Long-term follow-up and comparison regarding efficacy of these therapies is scarce. In this study the results of treatment, patient adherence, and satisfaction over a 10-year follow-up of these therapies are reported. This is a longitudinal follow-up study taken from a subset of patients initially enrolled in a randomized controlled clinical trial of 103 patients with OSA (51 and 52 patients randomized for MAD and CPAP, respectively). After a 10-year follow-up period, 14 patients using MAD and 17 patients using CPAP could be evaluated for this longitudinal follow-up study. Data were analyzed at baseline, after 3 months and at 1-, 2-, and 10-year follow-up. All 31 patients with OSA underwent polysomnography and self-reported measurements. Polysomnography results showed a favorable outcome of both therapies at 10-year follow-up. At baseline, included patients in both groups did not significantly differ in apnea-hypopnea index (AHI) values. At 10-year follow-up, both the MAD and CPAP groups showed a significant reduction in AHI. At baseline the mean AHI in the MAD group was 31.7 ± 20.6 events/h whereas in the CPAP group it was 49.2 ± 26.1 events/h. At 10-year follow-up the mean AHI in the MAD group was 9.9 ± 10.3 events/h and in the CPAP group it was 3.4 ± 5.4 events/h. Both therapies resulted in a substantial improvement in self-reported neurobehavioral outcomes at 10-year follow-up. Both CPAP and MAD therapy demonstrate good and stable treatment effects after a 10-year follow-up period. Therefore, when indicated, both therapies are appropriate modalities for the long-term management of OSA. Registry: Netherlands Trial Register; Name: Management of the Obstructive Sleep Apnea-Hypopnea Syndrome: Oral Appliance versus Continuous Positive Airway Pressure Therapy; Identifier: NL75; URL: https://www.trialregister.nl/trial/75.

Tests that now deserve to be more widely adopted in IBD clinical practice.

Inflammatory bowel diseases are chronic relapsing immune-mediated diseases of the intestinal tract with multifaceted manifestations and treatment related morbidity. Faecal and blood tests, radiological, endoscopic and histologic investigations are now widely used for managing both ulcerative colitis and Crohn’s disease. Over the years, a number of new investigations have been proposed but not widely adopted yet. Patients with Crohn’s disease may have multiple causes of diarrhoea, not always attributable to disease exacerbation, but sometimes linked to bile acid malabsorption; we have a reliable serum test, C4, that allows us to recognize and treat this cause of diarrhoea efficaciously and not empirically, but it is not available or used widely. There is genetic inter-individual variability in drug responses, in terms of both efficacy and toxicity, leading to high rates of therapeutic failure. Patients treated with thiopurine or, more rarely, 5-aminosalicylic acid may suffer from unpredictable and serious adverse events, some of these with pathogenesis related to genetic variants: myelosuppression, acute pancreatitis and nephrotoxicity. The identification of pre-treatment genetic tests can optimize therapeutic choice and avoid adverse events. With regard to biological drugs, patients can experience primary non-response or loss of response due to induction of immune responses to the drugs affecting drug efficacy and determining hypersensitivity reactions. We have specifically reviewed a number of investigations, whose use is currently limited, and highlighted four tests that deserve to be more widely incorporated in clinical practice as these could improve medical decision-making and patient outcomes.

Increased \u03b2-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study

BackgroundAugmented renal clearance (ARC) is recognized as a leading cause of β-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased β-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP).MethodsIn this single-center, retrospective study, every ARC patient treated by β-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome.ResultsDuring the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15–0.81), p = 0.014. No antibiotic side effect was reported during the treatment period.ConclusionsHigher than licensed dosing regimens of β-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.

Piperacillin-tazobactam should be preferred to third-generation cephalosporins to treat wild-type inducible AmpC-producing Enterobacterales in critically ill patients with hospital or ventilator-acquired pneumonia

PurposeTo compare the rate of therapeutic failure in critically ill patients treated by third-generation cephalosporins (3GCs) or piperacillin-tazobactam (PTZ) for wild-type AmpC-producing Enterobacterales pulmonary infections. MethodsOver a 4-year period, all adult patients treated for a wild-type AmpC-producing Enterobacterales pulmonary infection were retrospectively included. Two groups of patients were compared according to the definitive antibiotic therapy (3GCs or PTZ) considered after <48 h of empirical antibiotic therapy. The main outcome was the rate of therapeutic failure (impaired clinical response under treatment and/or a relapse of pulmonary infection). The secondary outcome was a secondary acquisition of 3GCs resistance. ResultsOver the study period, 244 patients were included; 56 (23%) experienced therapeutic failure. In the non-adjusted cohort, the rate of therapeutic failure and emergence of resistance were significantly higher in the 3GCs group (32 vs. 18%, p = .011 and 13 vs. 5%, p = .035, respectively). In the propensity score-matched population, the use of 3GCs was associated with higher rates of therapeutic failure (HR = 1.61 [1.27–2.07]). The secondary de-escalation to 3GCs after 48 h of PTZ as a first-line antibiotic therapy was not associated with increased rate of emergence of resistance. ConclusionOur study confirms that 3GCs should be avoided as first-line antibiotic therapy in wild-type AmpC-producing Enterobacterales pulmonary infections.

DALBACEN cohort: dalbavancin as consolidation therapy in patients with endocarditis and/or bloodstream infection produced by gram-positive cocci

ObjectivesTo analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact.MethodsA multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year.ResultsEighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism was Staphylococcus aureus in BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€).ConclusionsDBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.