Abstract
Background
Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). ...However, the two strategies have never been compared.
Methods
Data from two retrospective cohorts of ‘real-life’ use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis.
Results
Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; P = 0.03 and P < 0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71–2.96; P = 0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50–3.07; P = 0.64). Moreover, the multivariate analysis did not show differences depending on the drug used.
Conclusions
We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.
The aim of this study was to review recent data evaluating the management of central venous catheter-related bloodstream infection due to Gram-negative bacilli (GNB).
The incidence of GNB ...catheter-related bloodstream infection (CRBSI) has been increasing considerably in the last years, and this has raised a concern due to the high reported rate of multidrug-resistant in these infections what poses a considerable challenge for effective treatment. However, there are no specific guidelines for the management of GNB-CRBSI and optimal treatment duration has not been clearly defined. Recent studies have shown that the risk for complications is clearly different to what is stablished for Staphylococcus aureus . Therefore, a short course of antibiotic therapy might be effective once the central venous catheter (CVC) has been removed and the monitoring complications through control blood cultures or echocardiography seem to be less helpful in GNB CRBSI.
The incidence of GNB CRBSI has been increasing considerably in the last years; this has raised a concern due to the high reported rate of MDR in these infections what poses a considerable challenge for effective treatment. However, there are no specific guidelines for the management of GNB-CRBSI and optimal treatment duration has not been clearly defined. Recent studies have shown that the risk for complications is clearly different to what is stablished for S. aureus . Therefore, a short course of antibiotic therapy might be effective once the CVC has been removed and the monitoring complications through control blood cultures or echocardiography seem to be less helpful in GNB-CRBSI.
The SARS‐CoV‐2 VIrus PERsistence (VIPER) study investigated the presence of long‐lasting SARS‐CoV‐2 RNA in plasma, stool, urine, and nasopharyngeal samples in COVID‐19 survivors. The presence of ...SARS‐CoV‐2 RNA reverse transcription polymerase chain reactions (RT‐PCR) were analyzed within plasma, stool, urine, and nasopharyngeal swab samples in COVID‐19 survivors with post‐COVID symptoms and a comparison group of COVID‐19 survivors without post‐COVID symptoms matched by age, sex, body mass index and vaccination status. Participants self‐reported the presence of any post‐COVID symptom (defined as a symptom that started no later than 3 months after the initial infection). Fifty‐seven (57.9% women, age: 51.1, standard deviation SD: 10.4 years) previously hospitalized COVID‐19 survivors with post‐COVID symptoms and 55 (56.4% women, age: 50.0, SD: 12.8 years) matched individuals who had a past SARS‐CoV‐2 infection without post‐COVID symptoms were evaluated 27 (SD 7.5) and 26 (SD 8.7) months after hospital discharge, respectively. The presence of SARS‐CoV‐2 RNA was identified in three nasopharyngeal samples of patients with post‐COVID symptoms (5.2%) but not in plasma, stool, or urine samples. Thus, SARS‐CoV‐2 RNA was not identified in any sample of survivors without post‐COVID symptoms. The most prevalent post‐COVID symptoms consisted of fatigue (93%), dyspnea, and pain (both, 87.7%). This study did not find SARS‐CoV‐2 RNA in plasma, stool, or urine samples, 2 years after the infection. A prevalence of 5.2% of SARS‐CoV‐2 RNA in nasopharyngeal samples, suggesting a potential active or recent reinfection, was found in patients with post‐COVID symptoms. These results do not support the association between SARS‐CoV‐2 RNA in plasma, stool, urine, or nasopharyngeal swab samples and post‐COVID symptomatology in the recruited population.
Background
Immunomodulatory effects attributable to cytomegalovirus (CMV) would predispose to BK polyomavirus (BKPyV) infection after kidney transplantation (KT), although available evidence is ...conflicting. It has been suggested that (val)ganciclovir therapy may increase the risk of BKPyV viremia and BKPyV‐associated nephropathy (BKPyVAN) as a result of drug‐induced T‐cell impairment.
Methods
We investigated whether CMV replication and/or (val)ganciclovir exposure (either as prophylaxis or treatment) were associated with the development of BKPyV viremia or BKPyVAN in a prospective cohort of 399 KT recipients. CMV infection (any level or high‐level viremia and area under the curve of DNAemia) and (val)ganciclovir exposure (any duration of therapy and cumulative days of treatment) during the first post‐transplant year were explored through separate landmark survival analyses.
Results
Cumulative incidence of BKPyV viremia and BKPyVAN after a median follow‐up of 551 days was 23.1% and 2.5%, respectively. One‐year rates of CMV infection and (val)ganciclovir therapy were 47.4% and 54.1%, respectively. No differences were observed in BKPyV viremia‐ or BKPyVAN‐free survival according to previous CMV infection or (val)ganciclovir exposure in any of the landmark analyses. Adjusted Cox models confirmed this lack of association.
Conclusion
Our findings do not confirm the existence of a relevant impact of CMV infection or (val)ganciclovir therapy on the risk of post‐transplant BKPyV events.
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.
•Ceftazidime-avibactam (CAZ-AVI) is an effective and safe therapy for multidrug or extremely resistant (MDR/XDR) Pseudomonas aeruginosa infections•It is especially useful for strains with class A ...carbapenemase production•Early therapy with CAZ-AVI is associated with better outcomes•CAZ-AVI as part of combination therapy provides no clear benefits over monotherapy
Clinical experience with ceftazidime-avibactam (CAZ-AVI) for treatment of infections due to multidrug or extremely resistant (MDR/XDR) Pseudomonas aeruginosa (P. aeruginosa) is limited.
A retrospective cohort study was conducted on patients with MDR/XDR P. aeruginosa infections treated with CAZ-AVI. The primary outcome was clinical cure by day 14, evaluated by logistic regression adjusted for the propensity score to receive CAZ-AVI as combination therapy. Secondary outcomes were 30-day all-cause mortality, 90-day recurrence, emerging CAZ-AVI resistance, and safety of therapy.
Sixty-one first episodes of MDR/XDR P. aeruginosa infection were included. The most common source was lower respiratory tract infection (34.4%), 14.8% episodes developed bloodstream infection and 50.8% had sepsis at presentation. Ceftazidime-avibactam therapy was initiated at a median of 7.0 (interquartile range IQR: 3.5-12.0) days from symptom onset; it was used as combined therapy in 29 (47.5%) episodes. Clinical cure rate by day 14 was 54.1% and predictors of response were days to source control (adjusted odds ratio aOR: 0.84; 95% confidence interval CI: 0.72-0.98; P = 0.024), days until the initiation of CAZ-AVI therapy (aOR: 0.65; 95% CI: 0.49-0.86; P = 0.003), age (aOR: 1.07; 95% CI: 0.99-1.15; P = 0.066) and CAZ-AVI combination therapy (aOR: 0.02; 95% CI: 0.01-0.38; P = 0.009). Rates of 30-day all-cause mortality and 90-day recurrence were 13.1% and 12.5%, respectively. Emergence of drug resistance to CAZ-AVI was not detected. Treatment-related adverse events occurred in three episodes (4.9%).
CAZ-AVI constitutes a valid alternative for the treatment of infections due to MDR/XDR P. aeruginosa.
Isavuconazole has theoretical advantages over other mold-active triazoles for the treatment of invasive aspergillosis and mucormycosis after solid organ transplantation (SOT). The available clinical ...experience, nevertheless, is scarce.
We performed a retrospective study including all adult SOT recipients with proven or probable invasive mold disease (IMD) that received isavuconazole for ≥24 h as first-line or salvage therapy at 10 Spanish centers between September 2017 and November 2021. The primary efficacy outcome was clinical response (complete or partial resolution of attributable symptoms and findings) by weeks 6 and 12. Safety outcomes included the rates of treatment-emergent adverse events and premature isavuconazole discontinuation.
We included 81 SOT recipients that received isavuconazole for a median of 58.0 days because of invasive aspergillosis (n = 71) or mucormycosis (n = 10). Isavuconazole was used as first-line (72.8%) or salvage therapy due because of previous treatment-emergent toxicity (11.1%) or refractory IMD (7.4%). Combination therapy was common (37.0%), mainly with an echinocandin or liposomal amphotericin B. Clinical response by weeks 6 and 12 was achieved in 53.1% and 54.3% of patients, respectively, and was more likely when isavuconazole was administered as first-line single-agent therapy. At least 1 treatment-emergent adverse event occurred in 17.3% of patients, and 6.2% required premature discontinuation. Daily tacrolimus dose was reduced in two-thirds of patients by a median of 50.0%, although tacrolimus levels remained stable throughout the first month of therapy.
Isavuconazole is a safe therapeutic option for IMD in SOT recipients, with efficacy comparable to other patient groups.
Purpose
To know whether the production of OXA-48 carbapenemase exerts an independent impact on the outcome of
Klebsiella pneumoniae
infection, once adjusted by clinical syndrome and baseline risk ...factors.
Methods
We performed a case-cohort study including 117 infectious episodes due to OXA-48-producing
K. pneumoniae
(OXA-48-Kp) and 117 episodes due to non-OXA-48-producing strains (non-OXA-48-Kp). Both groups were matched (1:1 ratio) by clinical syndrome (source of infection, preceding invasive procedures and indwelling devices, and associated bacteremia) and hospitalization ward at infection onset. Multivariate Cox regression was used to investigate the association between OXA-48-Kp infection and clinical cure by day 14 (primary outcome) and 30-day all-cause mortality (secondary outcome).
Results
Both study groups were well balanced regarding underlying conditions and comorbidity burden. Sepsis or septic shock were more frequent in OXA-48-Kp cases than non-OXA-48-Kp controls (41 35.0% vs. 17 14.5%;
P-
value < 0.0001). Clinical cure by day 14 was less commonly achieved in OXA-48-Kp cases (49 41.9% vs. 95 81.2%;
P-
value < 0.001), whereas 30-day all-cause mortality was higher (33 28.2% vs. 18 15.4%;
P-
value = 0.018). Multivariate analysis confirmed that OXA-48-Kp infection was independently associated with the lack of 14-day clinical cure (adjusted hazard ratio aHR: 0.45; 95% confidential interval 95%CI: 0.29–0.70;
P-
value < 0.0001). A non-significant association was observed for 30-day all-cause mortality (aHR: 1.65; 95%CI: 0.92–2.94;
P-
value = 0.093).
Conclusion
Our matched analysis suggests that the production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in
K. pneumoniae
infection as compared to episodes due to non-carbapenemase-producing strains.
The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the ...long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations.
To describe the determinants of outcome of infections due to oxacillinase-48 (OXA-48) carbapenemase-producing Klebsiella pneumoniae (OXA-48-Kp).
A retrospective cohort study of 117 episodes of ...OXA-48-Kp infection were conducted. Multivariate Cox models identified factors predicting 14-day clinical response and 30-day all-cause mortality.
A total of 77 (65.8%) isolates were susceptible to imipenem/meropenem. The 14-day clinical response and 30-day mortality rates were 41.9% and 28.2%. Catheter-related bloodstream infection (adjusted hazard ratio aHR: 8.33; 95% confidence interval 95%CI: 3.19-21.72; P-value <0.001), urinary tract infection (aHR: 3.04; 95%CI: 1.39-6.66; P-value = 0.006) and early appropriate treatment (aHR: 1.77; 95%CI: 0.97-3.22; P-value = 0.064) predicted clinical response, whereas severe sepsis had a deleterious impact (aHR: 0.22; 95%CI: 0.10-0.50; P-value <0.001). Lower respiratory tract infection (aHR: 6.58; 95%CI: 2.83-15.29; P-value <0.001) and bloodstream infection (aHR: 2.33; 95%CI: 1.05-5.15; P-value = 0.037) were associated with 30-day mortality, whereas definitive therapy including ≥1 active agent (aHR: 0.26; 95%CI: 0.11-0.63; P-value = 0.003) and source control (aHR: 0.35; 95%CI: 0.14-0.91; P-value = 0.030) were protective. Combination therapy did not seem to be associated with better outcomes.
Appropriate antimicrobial treatment was protective for 30-day mortality in OXA-48-Kp infections. Carbapenems are usually active, whereas combination therapy appeared not to confer additional benefit.
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