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1.
Int J Mol Sci ; 24(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36902196

RESUMO

The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains presents a severe challenge to the healthcare system due to limited therapeutic options and high mortality. Since its availability, ceftazidime/avibactam (C/A) has become a first-line option against KPC-Kp, but C/A-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment. A retrospective, observational study was conducted with all patients admitted to the Intensive Care Unit (ICU) dedicated to COVID-19 patients at the City of Health & Sciences in Turin, between 1 May 2021 and 31 January 2022, with the primary endpoint to study strains with resistance to C/A, and secondly to describe the characteristics of this population, with or without previous exposure to C/A. Seventeen patients with colonization or invasive infection due to Klebsiella pneumoniae, C/A resistance, and susceptibility to meropenem (MIC = 2 µg/L) were included; the blaKPC genotype was detected in all isolates revealing D179Y mutation in the blaKPC-2 (blaKPC-33) gene. Cluster analysis showed that 16 out of the 17 C/A-resistant KPC-Kp isolates belonged to a single clone. Thirteen strains (76.5%) were isolated in a 60-day period. Only some patients had a previous infection with non-mutant KPC at other sites (5; 29.4%). Eight patients (47.1%) underwent previous large-spectrum antibiotic treatment, and four patients (23.5%) had prior treatment with C/A. The secondary spread of the D179Y mutation in the blaKPC-2 during the COVID-19 pandemic needs to be addressed constantly by an interdisciplinary interaction between microbiologists, infection control personnel, clinicians, and infectious diseases consultants to properly diagnose and treat patients.


Assuntos
Antibacterianos , Ceftazidima , Combinação de Medicamentos , Farmacorresistência Bacteriana , Infecções por Klebsiella , Klebsiella pneumoniae , Meropeném , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , beta-Lactamases/genética , COVID-19/epidemiologia , Unidades de Terapia Intensiva , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Meropeném/farmacologia , Meropeném/uso terapêutico , Testes de Sensibilidade Microbiana , Pandemias , Estudos Retrospectivos
2.
Arch Virol ; 167(8): 1669-1674, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35598207

RESUMO

The aim of this study was to evaluate plasmatic and urinary therapeutic drug monitoring (TDM) of tenofovir disoproxil fumarate (TDF) in a cohort of patients with chronic hepatitis B (CHB). In 68 enrolled patients, the estimated glomerular filtration rate (eGFR) was 68 mL/min in naive subjects, while in adefovir dipivoxil (ADV)-pretreated patients, it was 55.5 mL/min (p < 0.001). The HBV E genotype was associated with lower TDF levels (ß = -0.698, p < 0.001). The urinary TDF concentration was associated with ADV pretreatment (ß = 0.829, p < 0.001). Determination of urinary concentrations of TDF may be useful in the clinical management of older CHB patients and those with previous treatment with ADV.


Assuntos
Hepatite B Crônica , Antivirais/farmacologia , DNA Viral/genética , Farmacorresistência Viral , Quimioterapia Combinada , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Tenofovir/uso terapêutico , Resultado do Tratamento , Carga Viral
3.
Arch Virol ; 166(4): 1125-1131, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33580380

RESUMO

European clinical practice guidelines (EASL) on chronic hepatitis B (CHB) recently recognized the importance of migration flows in the changing hepatitis B virus (HBV) epidemiology in low-endemic European countries. The role of different genotypes in nucleos(t)ide analogue (NA) treatment is still unknown. In the case of genotype E, which is mainly circulating in West Africa, a quantitative decrease in the level of HBsAg (qHBsAg) during treatment with entecavir (ETV) predicts a longer time to HBsAg loss when compared to genotypes A and D. We prospectively evaluated qHBsAg decline in HBeAg-negative CHB patients infected with HBV genotype E who were treated with tenofovir 245 mg (TDF) or ETV 0.5 mg from 2008 to 2014. Sixty-five West African patients (58; 89.2% males) were enrolled. The median age was 29 years, and the most prevalent route of transmission was familial (25; 38.5%). Median liver stiffness was 7.4 kPa, HBV-DNA was 4.7 Log IU/ml, and qHBsAg was 3.4 Log UI/ml. According to clinical evaluation, 40 patients (61.5%) started ETV treatment, whereas 25 patients (38.5%) started TDF treatment. The decline of qHBsAg in ETV patients was significantly lower than in TDF patients after 5 years of treatment (0.31 vs. 0.68 LogIU/mL, p < 0.001). At the same time points, a significantly higher virological non-response rate was observed in ETV patients (p < 0.001). Despite the partial and non-response rates observed in the ETV group, no mutations associated with drug resistance were detected in these subjects. In genotype E infections, ETV treatment results in a significantly lower decline in qHBsAg and higher rates of virological non-response after 5 years. TDF could represent the optimal choice.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Feminino , Genótipo , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
4.
J Neurovirol ; 26(5): 642-651, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32737860

RESUMO

Highly active antiretroviral treatment has led to unprecedented efficacy and tolerability in people living with HIV. This effect was also observed in the central nervous system with the nowadays uncommon observation of dementias; yet in more recent works milder forms are still reported in 20-30% of optimally treated individuals. The idea of a subclinical neuronal toxicity induced by antiretrovirals has been proposed and was somehow supported by the late-emerging effects associated with efavirenz use. In this manuscript we are reviewing all the potential mechanisms by which antiretroviral drugs have been associated with in vitro, ex vivo, or in vivo toxicity to cells pertaining to the central nervous system (neurons, astrocytes, oligodendrocytes, and endothelial cells). These include direct or indirect effects and pathological pathways such as amyloid deposition, damage to small cerebral vessels, and impairment in neurotransmission. The aim of this review is therefore to provide a detailed description of the available literature in order to guide further clinical research for improving patients' neurocognition and quality of life.


Assuntos
Alcinos/toxicidade , Fármacos Anti-HIV/toxicidade , Benzoxazinas/toxicidade , Sistema Nervoso Central/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Ciclopropanos/toxicidade , Infecções por HIV/tratamento farmacológico , Neurônios/efeitos dos fármacos , Terapia Antirretroviral de Alta Atividade/métodos , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Astrócitos/virologia , Sulfato de Atazanavir/toxicidade , Sistema Nervoso Central/patologia , Sistema Nervoso Central/virologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/virologia , Didesoxinucleosídeos/toxicidade , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Células Endoteliais/virologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Neurônios/patologia , Neurônios/virologia , Nevirapina/toxicidade , Nitrilas/toxicidade , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Oligodendroglia/virologia , Pirimidinas/toxicidade
5.
J Med Virol ; 91(10): 1891-1895, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31199538

RESUMO

To assess the impact of genotypic susceptibility score (GSS) on combined antiretroviral therapy (cART) outcomes during primary HIV infection (PHI) we retrospectively enrolled patients with PHI diagnosed between 2008 and 2015 at 9/24 Italian Network ACuTe HIV InfectiON centers. One hundred-seventy-six patients were enrolled. Of these, 55 (32.9%) patients started with more than three drugs and 11 (7.2%) started with a GSS < 3. Regimen's GSS (per 1 point increase) (adjusted odds ratio [aOR], 4.82; 95% confidence interval [CI], 1.62-14.28; P = .005) and baseline HIV-RNA (per 1 log10 increase) (aOR, 2.02; 95% CI, 1.09-3.73; P = .025) resulted associated with early cART initiation. In conclusion, regimen's GSS resulted to be associated to the time to cART initiation during PHI.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV/genética , Adulto , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Microorganisms ; 12(4)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38674669

RESUMO

Ceftobiprole is a fifth-generation cephalosporin approved by European and American regulatory agencies for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). Ceftobiprole administration is useful in severe CAP as well as HAP where the potential is to save other ß-lactams including carbapenems or linezolid/vancomycin in clinical practice. The aim of this study was to report the real-world evidence of ceftobiprole in patients with CAP and HAP in a single center. In this retrospective study, we included 159 patients with CAP or HAP: 105 (66%) had CAP and 54 (34%) had HAP. The median age was 70 years (IQR 60-77), the median Charlson Comorbidity Index was 5 (IQR 3-7.5) and baseline INCREMENT ESBL score was 8 (IQR 6-11). Ceftobiprole was mostly given as a combination treatment (77%) or as a carbapenem-sparing strategy (44%). There were no differences in mortality between shorter and longer duration of treatment (<7 days compared with ≥7 days (HR 1.02, C.I. 0.58-1.77, p = 0.93) or between first-line (HR 1.00, C.I. 0.46-2.17, p = 0.989) and second-line therapy. Ceftobiprole use in CAP or HAP in the real world is effective as a first- and second-line treatment as well as a carbapenem-sparing strategy. Further studies are needed to explore the full potential of ceftobiprole, including its real-world use in antimicrobial stewardship programs.

8.
Life (Basel) ; 14(2)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38398779

RESUMO

Left ventricular assist devices (LVADs) have been increasingly used as a valid option to improve the prognosis and reduce the symptoms of end-stage heart failure. However, long-term complications, mostly infections and coagulation disorders, are frequent. We described the epidemiology and risk factors for nosocomial infections (NIs) in a cohort of adult patients who underwent continuous-flow LVAD implant between January 2010 and December 2017 in Turin, Italy. Secondary outcomes were the prevalence of multidrug-resistant (MDR) bacteria and mortality. Results: Overall, 64 LVADs were implanted. A total of 32 (50%) patients experienced at least one episode of NI, with a total of 46 infectious events. VAD-related infections occurred in 22 patients (68.8%). Non VAD-related NIs occurred in 12 patients (37.5%), mainly low respiratory tract infections. Length of intensive care unit admission was a risk factor for NI (OR 1.224, 95%CI; 1.049, 1.429). Gram-negative bacilli were responsible for 58.8% of VAD-related infections and 79.5% of non-VAD related infections. In sixteen patients (50%), at least one episode of infection was related to an MDR strain. INTERMACS class and length of MV were independent risk factors for NIs by MDR strains (respectively, OR 2.12, 95%CI: 1.08, 6.80; p = 0.02 and OR 1.46, 95%CI: 1.07, 5.52, p = 0.047). In-hospital mortality was 6.3%. No differences in mortality were observed between infected and non-infected patients (p = 0.61) even when caused by MDR strains (p = 0.143). Conclusion: the rate of nosocomial infections in LVAD patients is associated with the length of ICU admission, and the etiology of nosocomial infection after LVAD implant is mainly due to GNB, including a high rate of MDR strains, especially KPC-KP and MDR PA.

9.
Open Forum Infect Dis ; 11(6): ofae273, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38854388

RESUMO

Background: Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam. Methods: We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality. Results: The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy. Conclusions: Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy.

10.
Life (Basel) ; 13(4)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37109488

RESUMO

Oritavancin is a long-acting lipoglycopeptide with in vitro activity against Gram-positive pathogens, as well as good bactericidal activity and sterilisation ability in biofilm. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, such as for vancomycin resistant enterococci (VRE), deep-seated infections including those involving prosthetic material and invasive infections. The aim of this work is to review the uses of oritavancin outside of ABSSSI, focusing on its real-life applications on infective endocarditis, catheter- or device-related infections, bloodstream infections, and bone and prosthetic joint infections in humans, as well as possible future applications. We performed a narrative review, collecting the literature published between 1 December 2002 and 1 November 2022 on PubMed and the Cochrane Library using the term 'oritavancin'. Available studies have shown how effective it is in different settings, suggesting an opportunity for step-down strategies or outpatient management of infections requiring a long duration of antibiotic treatment. So far, evidence is still scarce, and limited to a few studies and case reports, mostly focusing on Staphylococcus aureus as the major isolate. Concerns about fluid intake for dilution and interaction with coagulation markers also need to be taken into account. Further studies are required in order to assess the safety and effectiveness of Oritavancin in vascular, prosthetic, or device-related infections, as well as in resistant Gram-positive bacteria or enterococcal infections.

11.
Microorganisms ; 11(5)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37317076

RESUMO

BACKGROUND: Evidence has shown that short courses of antibiotic therapy are at least as effective as long courses with better clinical outcomes. CAZ/AVI has demonstrated its clinical efficacy in treating K. pneumoniae-KPC infections. METHODS: We conducted an analysis based on the real-life data of our ten years retrospective cohort to assess the cost-effectiveness and cost-utility of a short course of CAZ/AVI plus source control compared to a long course plus source control. A Markov model was structured. Patient transition between health states was modeled, each transition has a probability, and each state has a cost and a utility. Incremental cost-effectiveness ratios (ICERs) were obtained by dividing the difference in costs by the difference in utilities between the two courses. Input parameter uncertainty was investigated through sensitivity analysis. We launched 1000 Monte Carlo simulations by iteratively perturbing variables within estimated variation ranges, obtaining an ICER result for each simulation. RESULTS: In the first model (old appropriate treatment), a short course of treatment was associated with reduced costs per patient per year of €4818.60 and reduced effects (0.10 QALYs), compared to a long course. In the CAZ/AVI model, the short course was associated with increased costs of €1297.9 and with increased effects (0.04 QALYs), resulting in an ICER of €32,317.82 per QALY gained, below the WTP threshold of €40,000. CONCLUSIONS: Our findings highlight additional evidence regarding the cost-effectiveness of CAZ/AVI for policy-makers. We outline that CAZ/AVI could be cost-effective compared to old appropriate antibiotic therapies for KPC-Kp BSI.

12.
Microorganisms ; 11(2)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36838463

RESUMO

Legionella pneumophila (LP) is one of the main causative agents of community-acquired pneumonia in Europe and its fifth bacterial cause in Italy (4.9%). We conducted a seven year retrospective analysis of LP infection serogroup 1 in Asti, Piedmont, between 2016 and 2022. Patients were included if they tested positive for the Legionella urinary antigen. Clinical, laboratory, and radiologic data were analyzed to describe the risk factors for mortality. Fifty patients with LD were collected, mainly male, with a median age of 69 years. The main comorbidities were cardiovascular diseases (50%), pulmonary diseases (26%), and neurological diseases (12%). The most common clinical presentations were fever, respiratory, gastrointestinal, and neurologic symptoms. Older age (p = 0.004), underlying cardiovascular diseases (p = 0.009), late diagnosis at admission (p = 0.035), and neurological symptoms at diagnosis (p = 0.046) were more common in the non-survivor group. Moreover, a septic-shock presentation or the need for non-invasive ventilation at admission were associated with a higher mortality. No considerable differences in the biochemical data were found between the two groups except for the median neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, and PCT value. We did not find any differences in mortality related to the choice of antibiotic regimen. Differences in outcome were associated with the median duration of treatment (p =< 0.001) but not to the choice of antibiotic regimen (mainly levofloxacin or azithromycin). In conclusion, early individuation of the wide spectrum of clinical characteristics of LP infection such as respiratory, cardiac, and neurological manifestations of the patient's comorbidities, and significant biochemical data should help clinicians flag high risk patients and potentially improve their outcome.

13.
Infez Med ; 31(3): 407-410, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37701394

RESUMO

We report the case of a 58-year-old male with a recent diagnosis of HIV infection admitted for progressive muscular weakness and psychomotor impairment. Cerebrospinal examination documented a mild hyperproteinorrachia, with normal cells count and reduced glycorrhachia. Brain gadolinium-enhanced MRI showed bilateral T2 and FLAIR hyperintensities in the nucleo-capsular region and irregular contrast-enhancement of the globi pallidi and the right putamen. The histologic analysis of a quadriceps biopsy showed several foci of inflammatory infiltrates with concomitant muscular fiber atrophy and degeneration. Scattered intracytoplasmic inclusions were observed in muscle fibers, representing the main pathological feature. A positive PCR for Toxoplasma gondii and a Toxoplasma gondii specific monoclonal antibody immunohistochemical staining confirmed the diagnosis.

14.
Trop Med Infect Dis ; 8(7)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37505654

RESUMO

Strongyloides and cytomegalovirus co-infections are rarely reported, even though they are distinguished by high morbidity and mortality, especially in immunocompromised hosts. We narratively reviewed the literature on reported cases of Strongyloides and CMV co-infections in immunosuppressed patients. Most cases occurred in males with a median age of 47 (IQR, 37-59). Strongyloides/CMV co-infections occurred among immunocompromised hosts, especially in solid organ transplants and hematological or rheumatological diseases. Most of the patients underwent a course of steroid treatment before the diagnosis of co-infections. Other common immunomodulatory agents were tacrolimus and mycophenolate. The first clinical manifestations of co-infections were mainly gastrointestinal, followed by respiratory symptoms. CMV was, in most patients, co-infected with an isolated reactivation, although Strongyloides manifested especially as hyperinfection syndrome. Ganciclovir and ivermectin are the mainstays of CMV and Strongyloides treatment. However, the treatment mortality reported in this narrative review is around 52.4%. Interestingly secondary bacterial infections are common in CMV/Strongyloides-infected patients.

15.
Trop Med Infect Dis ; 8(6)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37368749

RESUMO

To our knowledge, we have described the first case of Strongyloides/Cytomegalovirus (CMV) concomitant infection that occurred in a European country. The patient was a 76-year-old woman affected by relapsed non-Hodgkin lymphoma who presented interstitial pneumonia with a rapidly progressive worsening of respiratory insufficiency, leading to cardiac dysfunction and consequent death. CMV reactivation is a common complication in immunocompromised patients, while hyperinfection/disseminated strongyloidiasis (HS/DS) is rare in low endemic regions, but has been widely described in Southeast Asia and American countries. HS and DS are two consequences of the failure of infection control by the immune system: HS is the uncontrolled replication of the parasite within the host and DS the spreading of the L3 larvae in organs other than the usual replication sites. Only a few cases of HS/CMV infection have been reported in the literature, and only in one patient with lymphoma as an underlying disease. The clinical manifestations of these two infections overlap, usually leading to a delayed diagnosis and a consequent poor outcome.

16.
Infez Med ; 30(2): 242-246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693064

RESUMO

Bacillus Calmette-Guerin (BCG) is commonly and safely used as intravesical instillation to treat bladder cancer. Adverse effects are widely described in case report and series with a broad range of clinical presentations known as "BCGitis". Moreover, microbiological identification is often inconclusive leading to diagnostic uncertainty and no standardisation of definitions is available. We retrospectively collected all cases of BCGitis (n=19) after BCG intravesical administration occurred in 2 major Italian hospitals in the last 10 years. Median age was 71.8 years and among comorbidities hypertension affected 60% of patients. The delay in the onset of symptoms was < one week and an inverse correlation was observed between the number of instillations and the time to the onset of symptoms. Moreover, a febrile presentation was the commonest clinical symptom (85%) and an interstitial or micronodular pattern at chest X-ray or CT scan was found positive in about 70% and 90% of cases, respectively. Larger cohorts are needed in order to inform clinically relevant algorythms for this uncommon disease.

17.
Infez Med ; 30(4): 570-576, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36482960

RESUMO

Background: Since the emergence of the pandemic of SARS-CoV-2, a high reported incidence of VAP in COVID-19 sustained by carbapenem resistant Acinetobacter baumannii (CRAB) has been observed, but data are scarce to date. Materials and methods: We retrospectively collected COVID-19 patients who developed CRAB-VAP - defined according to Center for Diseases Control (CDC) 2020 criteria and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) or Infectious Diseases Society of America (IDSA) guidelines - to describe characteristics and outcome. Results: Among 21 patients with CRAB-VAP in COVID-19, median age was 66 years (IQR 41-80). Median time of VAP-onset was 7 days (IQR 0-28 days) from ICU - admission and 76.2% had septic shock. Treatment regimens were all colistin-based, in 28% (n=6) including ampicillin/sulbactam and rifampicin. In three cases, cefiderocol was started as rescue. Survival rate at 28-days was 35% (n=7). Conclusion: Non-fermenting Gram-negative bacteria are an emerging aetiology of VAP in COVID-19 patients. This underscores the urgent need for proper microbiological identification to address therapies and infection control protocols.

18.
J Infect Public Health ; 15(9): 975-979, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35961239

RESUMO

OBJECTIVES: To date limited information about cefiderocol use is provided by real life studies. Our aim is to evaluate characteristics and outcome of patients with Gram-negative infections with limited therapeutic options treated with cefiderocol in combination or monotherapy. METHODS: We retrospectively collected data on demographical, clinical characteristics and clinical cure, in-hospital and 30-days mortality, microbiological failure and Clostridioides difficile infections of all patients ≥ 18 years old treated with cefiderocol for ≥ 48 h. RESULTS: There were 18 patients of which 14 (77.8%) treated with cefiderocol in combination and 4 (22.2%) with monotherapy. Median age was 54.5 (IQR 35.25-65.75) vs 70.5 (IQR 57.5-78.25) years old, respectively and ward of admission was the ICU in the 78.57% vs 100% of cases. In the 50% vs 100% of cases infections were VAP with concomitant bloodstream infections. Median SOFA score was 10 (IQR 4.5-12.5) vs 5 (IQR 4-6) and APACHE II score was 13.5 (IQR 7.5-18) vs 16 (IQR 8.5-23.5), respectively. Isolated pathogen was carbapenems-resistant Acinetobacter baumannii in 78.57% vs 100% of cases. Median duration of cefiderocol treatment was 9.5 (IQR 7-13.25) vs 9 days (IQR 5.5-12.5) and in 77.8% patients it was used in combination therapy, of which 57.1% were colistin-spairing regimens. Clinical cure was achieved in 64.29% for combination therapy vs 75% of monotherapy treated patients, 30-days mortality rate was 28.57% vs 25% and 30-day ICU admission rate was 14.29% vs 50%, respectively. No statistically significant differences were observed between combination therapy and monotherapy treated patients. CONCLUSIONS: To date, no differences have been demonstrated between cefiderocol monotherapy or combination. Further studies are required to understand whether cefiderocol combination therapy could provide an advantage in outcome in seriously-ill patients.


Assuntos
Antibacterianos , Cefalosporinas , Adolescente , Idoso , Antibacterianos/farmacologia , Cefalosporinas/uso terapêutico , Colistina/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Cefiderocol
19.
Antibiotics (Basel) ; 11(4)2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35453244

RESUMO

Temocillin is an old antibiotic, but given its particular characteristics, it may be a suitable alternative to carbapenems for treating infections due to ESBL-producing Enterobacterales and uncomplicated UTI due to KPC-producers. In this narrative review, the main research question was to summarize current evidence on temocillin and its uses in infectious diseases. A search was run on PubMed using the terms ('Temocillin' [Mesh]) AND ('Infection' [Mesh]). Current knowledge regarding temocillin in urinary tract infection, blood-stream infections, pneumonia, intra-abdominal infections, central nervous system infections, skin and soft tissues infections, surgical sites infections and osteoarticular Infections were summarized. Temocillin retain a favourable profile on microbiota and risk of Clostridioides difficile infections and could be an option for treating outpatients. Temocillin may be a valuable tool to treat susceptible pathogens and for which a carbapenem could be spared. Other advantages in temocillin use are that it is well-tolerated; it is associated with a low rate of C. difficile infections; it is active against ESBL, AmpC, and KPC-producing Enterobacterales; and it can be used in the OPAT clinical setting.

20.
Antibiotics (Basel) ; 11(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35052933

RESUMO

BACKGROUND: infective endocarditis (IE) remains a severe disease frequently encountered in clinical practice and often requiring interdisciplinary medical and surgical management. This national survey aims to describe the clinical prescribing habits of the use of daptomycin in the setting of IE and the possible role for combination therapy with beta-lactams. METHODS: The study was a cross-sectional internet-based questionnaire survey on therapy with daptomycin. The questionnaire was designed with closed-ended questions and distributed using the SurveyMonkey® platform between October 2019 to December 2020. RESULTS: 55 clinicians from twelve Italians regions joined the questionnaire. The survey reported use of daptomycin as first-line choice in 31.48% of cases and as the first-line anti-MRSA agent in 44.44%. The empiric use of daptomycin was stated in the high suspicion of MRSA rather than MSSA, enterococcal or streptococcal IE. The rationale of daptomycin for the empirical treatment of native and prosthetic valve IE was mostly the possibility of administering an aminoglycoside-sparing combination regimen, high bacterial killing rate and high clinical efficacy. CONCLUSIONS: In conclusion, in selected patients, daptomycin could be a feasible option for the treatment of infective endocarditis in line with data from the European registry of daptomycin.

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