Lamivudine plus dolutegravir as a switch strategy in children: three case reports.

Lamivudine (3TC)/dolutegravir (DTG) single tablet regimen (STR) has shown long-term efficacy and tolerability in people living with HIV (PLWH). Dolutegravir has been approved for use in children, while data on the efficacy of 3TC plus DTG in maintaining virological suppression in this population are still under evaluation. In this case series, we describe three children with perinatally acquired HIV who maintained virological suppression after switching antiretroviral therapy to DTG/3TC. We present three case reports of three children enrolled in the Italian Register for HIV Infection in Children: a 9-year-old boy, a 10-year-old girl, and a 2-year-old girl with perinatally acquired HIV who immediately started antiretroviral therapy with a three-drug regimen upon diagnosis, which occurred at delivery, after 6 months of life, and after 2 years of life, respectively. They achieved and maintain virological suppression after 1, 6, and 7 months of therapy, respectively; then a switch strategy was performed with a two-drug regimen with DTG/3TC STR at the age of 7 years for the first child and at the age of 9 years for the second, while the third was switched to a DTG plus 3TC not STR, owing to weight requirements, at the age of 2 years and 10 months. All children maintained virological suppression at last follow-up visit (January 2024), showing an excellent growth curve and maintaining good adherence and tolerability to DTG plus 3TC. A two-drug regimen with DTG/3TC demonstrated efficacy in maintaining virological suppression in a switch strategy in these children, with important advantages such as better tolerability and comfort of taking a single tablet once daily.

Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA Registry.

Not available.

Weight Gain in Overweight and Obese People with HIV-The OBHIV Cohort.

BACKGROUND: HIV and non-HIV-related factors have been related to weight gain (WG); however, their specific impact on people with HIV (PWH) who are overweight or obese remains unclear. METHODS: This is a single-center observational study enrolling PWH with a BMI > 25 kg/m2. A generalized linear model was used to assess variables related to greater WG during 12 years of observation. RESULTS: A total of 321 PWH were enrolled, 67% overweight and 33% obese, who gained an average of 0.2 ± 1.3 and 1.7 ± 1.5 kg/year, respectively (p < 0.0001). Years since HIV infection were the only variable significantly associated with WG (ß -0.048, 95% CI -0.083; -0.013) during the study period, while type of ART did not influence the outcome. Narrowing the observation to the period of the SARS-CoV-2 pandemic, PWH with a longer duration of infection (ß 0.075, 95% CI 0.033; 0.117) and a greater increase in triglycerides (ß 0.005; 95% CI 0.000; 0.011) gained more weight, while higher BMI (ß -0.256, 95% CI -0.352; -0.160), obesity (ß -1.363, 95% CI -2.319; -0.408), diabetes mellitus (ß -1.538, 95% CI -2.797; -0.278), and greater abdominal circumference (ß -0.086, 95% CI -0.142; -0.030) resulted in protection. CONCLUSION: Among overweight and obese PWH, the amount of WG was higher in the first years after diagnosis of HIV and decreased thereafter, despite aging, regardless of the type of ART.

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

Lower (1,3)-beta-d-glucan sensitivity and in vitro levels in Candida auris and Candida parapsilosis strains.

OBJECTIVES: The serum (1,3)-beta-d-glucan (BDG) assay gives quicker results and has higher sensitivity than blood cultures, therefore it is advised for early diagnosis of invasive candidemia and/or discontinuation of empirical therapy. Its sensitivity may depend on different factors. The aim of our study was to analyse the in vitro and in vivo BDG levels in clinical isolates of three species of Candida responsible for candidemia. METHODS: C. albicans, C. parapsilosis, and C. auris strains were collected from blood cultures of patients who had a concurrent (-1 to +3 days) serum BDG test (Fungitell assay). Supernatants of all strains were tested in quadruplicate for BDG levels. RESULTS: Twenty-two C. auris, 14 C. albicans, and ten C. parapsilosis strains were included. The median BDG levels in supernatants were 463 pg/mL (interquartile range [IQR] 379-648) for C. auris, 1080 pg/mL (IQR 830-1276) for C. albicans, and 755 pg/mL (IQR 511-930) for C. parapsilosis, with the significant difference among the species (p < 0.0001). Median serum BDG levels (IQR) were significantly lower in case C. auris and C. parapsilosis vs. C. albicans (p < 0.0001), respectively, 50 pg/mL (IQR 15-161) and 57 pg/mL (IQR 18-332), vs. 372 pg/mL (IQR 102-520). Sensitivity of serum BDG was 39% (95% confidence interval [CI], 18-64) in case of C. auris, 30% (95% CI, 8-65) C. parapsilosis and 78% (95% CI, 49-94) C. albicans candidemia. DISCUSSION: In our centre C. auris and C. parapsilosis strains have lower BDG content as compared with C. albicans, with a potential impact on serum BDG performance for the diagnosis of candidemia.

Amoebic Liver Abscess: Potential Application of New Diagnostic Techniques for an Old Pathogen.

Amoebic liver abscess is a severe and potentially life-threatening infection requiring prompt diagnosis and early targeted treatment. Diagnosis is challenging because conventional diagnostic methods such as light microscopy and serology are often unreliable. Molecular techniques have emerged as an additional diagnostic tool, suddenly becoming the new diagnostic reference standard. More recently, commercial multiplex PCR panels, including FilmArray, have been introduced, which permit the simultaneous detection of several enteric pathogens including Entamoeba histolytica in stool samples. We report a case of an amoebic liver abscess promptly diagnosed by FilmArray gastrointestinal panel performed on liver drainage fluid.

Antibiotic Strategies for Severe Community-Acquired Pneumonia.

Despite advancements in health systems and intensive care unit (ICU) care, along with the introduction of novel antibiotics and microbiologic techniques, mortality rates in severe community-acquired pneumonia (sCAP) patients have not shown significant improvement. Delayed admission to the ICU is a major risk factor for higher mortality. Apart from choosing the appropriate site of care, prompt and appropriate antibiotic therapy significantly affects the prognosis of sCAP. Treatment regimens involving ceftaroline or ceftobiprole are currently considered the best options for managing patients with sCAP. Additionally, several other molecules, such as delafloxacin, lefamulin, and omadacycline, hold promise as therapeutic strategies for sCAP. This review aims to provide a comprehensive summary of the key challenges in managing adults with severe CAP, focusing on essential aspects related to antibiotic treatment and investigating potential strategies to enhance clinical outcomes in sCAP patients.

Lower blood levels of isavuconazole in critically ill patients compared with other populations: possible need for therapeutic drug monitoring.

BACKGROUND: Isavuconazole is first-line treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) is deemed not necessary, since most patients reached therapeutic levels (>1 mg/L) in large studies. Low levels were reported in some critically ill patients admitted to the ICU. The aim was to compare isavuconazole levels between critically ill and non-critically ill patients. MATERIALS AND METHODS: Retrospective analysis of data from all patients treated with standard-dose isavuconazole between 1 January 2019 and 26 October 2022 was performed. The following data were collected: TDM results from the first 30 days of therapy; ward of admission; demographic and clinical characteristics; continuous renal replacement therapy; extracorporeal membrane oxygenation; and co-administered drugs. RESULTS: Seventy-two patients (median age 65 years) and 188 TDM measurements (mean number of samples per patient 2.6 ±â€Š1.7) were included; 33 (45.8%) were ICU patients (3 also had haematological disorders); 39 (54.2%) were non-ICU patients, of whom 31 had haematological disorders. In all patients, the mean isavuconazole blood level was 3.33 ±â€Š2.26 mg/L. Significantly lower levels were observed in the ICU versus the non-ICU population: mean 2.02 ±â€Š1.22 versus 4.15 ±â€Š2.31 mg/L (P < 0.001). Significantly higher rates of subtherapeutic levels were observed in ICU patients compared with the non-ICU population: all determinations <2 mg/L in 33.3% versus 7.7%, and all determinations <1 mg/L in 12.1% versus 0%, respectively. Predictors of lower isavuconazole levels were admission to the ICU, BMI > 25 kg/m2, bilirubin > 1.2 mg/dL and the absence of haematological disorder. CONCLUSIONS: ICU patients had significantly lower isavuconazole blood levels compared to non-ICU population. The TDM of isavuconazole for efficacy should be performed in ICU.

Unresolved issues in the diagnosis of catheter related candidemia: A position paper / Cuestiones no resueltas en el diagnóstico de la candidemia relacionada con el catéter: un documento de opinión

The incidence and recent trends of candidemia and the contribution of the COVID-19 pandemic to its evolution are not well documented. The catheter is a major focus of Candida spp. infections, but the methods used to confirm the origin of candidemia are still based on the data generated for bacterial infection. The presence of Candida spp. on the tip of a removed catheter is the gold standard for confirmation but it is not always possible to remove it. Conservative methods, without catheter removal, have not been specifically studied for microorganisms whose times of growth are different from those of bacteria and therefore these results are not applicable to candidemia. The different Candida species do not have a particular tropism for catheter colonization and fungal biomarkers have not yet been able to contribute to the determination of the origin of candidemia. Techniques such Candida T2 Magnetic Resonance (T2MR) has not yet been applied for this purpose. Finally, there is not yet a consensus of how to proceed when Candida spp. is isolated from an extracted catheter and blood cultures obtained from simultaneous peripheral veins are negative. In this lack of firm data, a group of experts has formulated a series of questions trying to answer them based on the literature, indicating the current deficiencies and offering their own opinion. All authors agree with the conclusions of the manuscript and offer it as a position and discussion paper. (AU)

La incidencia y las tendencias recientes de la candidemia y la contribución de la pandemia de COVID-19 a su evolución no están bien documentadas. El catéter es uno de los principales focos de infecciones por Candida spp., pero los métodos empleados para confirmar el origen de la candidemia siguen basándose en los datos generados para la infección bacteriana. La presencia de Candida spp. en la punta de un catéter retirado es el método de referencia para la confirmación, pero no siempre es posible proceder a dicha retirada. Los métodos conservadores, sin retirada del catéter, no han sido estudiados específicamente para microorganismos cuyos tiempos de crecimiento son diferentes a los de las bacterias y, por tanto, estos resultados no son aplicables a la candidemia. Las diferentes especies de Candida spp. no tienen un tropismo particular para la colonización del catéter y los biomarcadores fúngicos, aún no han podido contribuir a la determinación del origen de la candidemia. Técnicas como la resonancia magnética T2MR todavía no se ha empleado para este fin. Por último, todavía no existe un consenso sobre cómo proceder cuando se aísla Candida spp. en un catéter extraído y los hemocultivos obtenidos por venas periféricas simultáneas son negativos. Ante esta falta de datos firmes, un grupo de expertos ha formulado una serie de preguntas y ha tratado de responderlas en base a la literatura, indicando las carencias presentes y ofreciendo su propia opinión. Todos los autores están de acuerdo con las conclusiones del manuscrito y lo ofrecen como documento de posición y discusión. (AU)

Clinical characteristics and outcomes of vaccinated patients hospitalised with SARS-CoV-2 breakthrough infection: Multi-IPV, a multicentre study in Northern Italy.

BACKGROUND: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. METHODS: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson's Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. RESULTS: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039-0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582-1.703, p = 0.987). CONCLUSIONS: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

Emerging treatment options for skin and soft tissue infections tailoring drug selection to individual patients.

PURPOSE OF REVIEW: To provide a brief overview of drugs in Phase II and III of development for the treatment of acute bacterial skin and skin structure infections (ABSSSI), offering insights into potential customized treatment options. RECENT FINDINGS: Several drugs are currently in advanced stages of evaluation for the treatment of ABSSSI, and numerous molecules are entering in the early development phases. Notably, many of these drugs exhibit unique mechanisms of action and interesting antimicrobial spectrum. SUMMARY: Tailoring antibiotic therapy based on patient characteristics, likely pathogens, type, site and severity of ABSSSI is crucial. Given the inherent limitations of available treatments, the development of novel agents is a pivotal avenue. Such advancements hold promise for enhancing treatment efficacy and simplifying drug selection for ABSSSI in everyday clinical practice.

Natural history and prognostic factors of candidemia in kidney transplant recipients: A retrospective, multinational study.

BACKGROUND: The natural history of candidemia in kidney transplant recipients (KTR) remains poorly understood. This study aimed to evaluate mortality, prognostic factors and overall graft loss after candidemia in KTRs. METHODS: This is a retrospective multicentre study enrolling all KTRs ≥15 years old with candidemia diagnosed at hospitals in Brazil, Spain and Italy from 2010 to 2020. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors of 14-day mortality and overall graft loss. RESULTS: We enrolled 93 KTRs of which 75 were from Brazil. The mean time interval from transplantation to the onset of candidemia was 45.2 ± 61.5 months. 42% of all patients were on haemodialysis, 31.3% had an episode of sepsis and 39% underwent surgery within 30 days before fungemia. European patients were more likely to receive echinocandin (32 vs. 72%, p < .001). 22.7% of Brazilian patients did not receive any antifungal before death. All-cause mortality at 14 days was higher in Brazil (41.3 vs. 11.1%, p = .016). Candida colonisation (OR 6.91 [95% CI: 1.08-44.3], p = .042) and hypotension (OR 4.87 [95% CI: 1.62-14.66], p = .005) were associated with 14-day mortality. Echinocandin treatment had a protective effect (OR 0.19 [95% CI: 0.05-0.73], p = .015). Graft loss at 90 days occurred in 48% of patients (70.7 in Brazil vs. 22.2% in Europe, p < .01). CONCLUSIONS: Candidemia in KTR is usually documented late after engraftment in patients requiring HD, surgical procedures and dysbiosis secondary to antibiotic use. Mortality was higher in Brazil. Echinocandin therapy was associated with improved survival.

Laboratory and clinical management capacity for invasive fungal infections: the Italian landscape.

BACKGROUND: We assessed the laboratory diagnosis and treatment of invasive fungal disease (IFD) in Italy to detect limitations and potential for improvement. METHODS: The survey was available online at www.clinicalsurveys.net/uc/IFI management capacity/, and collected variables such as (a) institution profile, (b) perceptions of IFD in the respective institution, (c) microscopy, (d) culture and fungal identification, (e) serology, (f) antigen detection, (g) molecular tests, (h) susceptibility testing and (i) therapeutic drug monitoring (TDM). RESULTS: The laboratory capacity study received responses from 49 Italian centres, with an equitable geographical distribution of locations. The majority of respondents (n = 36, 73%) assessed the occurrence of IFD as moderate-high, with Aspergillus spp. being the pathogen of highest concern, followed by Candida spp. and Mucorales. Although 46 (94%) of the institutions had access to microscopy, less than half of them performed direct microscopy on clinical specimens always when IFD was suspected. Cultures were available in all assessed laboratories, while molecular testing and serology were available in 41 (83%), each. Antigen detection tests and antifungal drugs were also generally accessible (> 90%) among the participating institutions. Nevertheless, access to TDM was limited (n = 31, 63%), with a significant association established between therapeutic drug monitoring availability and higher gross domestic product per capita. CONCLUSIONS: Apart from TDM, Italy is adequately prepared for the diagnosis and treatment of IFD, with no significant disparities depending on gross domestic product. Future efforts may need to focus on enhancing the availability and application of direct microscopic methods, as well as TDM, to promote optimal treatment and better patient outcomes.

Neutralizing monoclonal antibodies for the prevention of severe COVID-19: a retrospective study during Omicron BA.1 variant surge.

Among treatment options for Coronavirus disease 2019 (COVID-19), monoclonal antibodies (mAbs) showed to be effective in preventing disease progression, but real-world data during the Omicron variant surge are still lacking. Multicentre retrospective study evaluating the effectiveness of sotrovimab and casirivimab-imdevimab in fragile patients with mild SARS-CoV-2 infection between November 2021 and March 2022. Unfavourable outcome was defined as increased need for oxygen supplementation and/or death. Of 268 study-participants, 12 (4.48%) previously needed supplemental oxygen, while 6 (2.24%) had active solid neoplasia (2.24%); 186 (69%) have previously received SARS-CoV-2 vaccination. Overall, 22 (8%) had unfavourable outcomes (42% versus 6% of patients with and without previous oxygen need and 50% versus 7% of patients with and without active solid neoplasia). Both supplemental oxygen therapy before SARS-CoV-2 infection and solid malignant tumour have shown to be risk factors for treatment failure. Log-rank test did not identify differences between sotrovimab and casirivimab-imdevimab treatment. Despite diffusion of Omicron variant, the rate of unfavourable outcome was higher than expected. The presence of underlying risk factors, including solid cancer and previous oxygen therapy are independently associated with risk of COVID-19 progression, suggesting the need for antiviral treatments not limited to mAbs and implementation of vaccine campaign.

Early diagnosis of candidemia with explainable machine learning on automatically extracted laboratory and microbiological data: results of the AUTO-CAND project.

BACKGROUND: Candidemia is associated with a heavy burden of morbidity and mortality in hospitalized patients. The availability of blood culture results could require up to 48-72 h after blood draw; thus, early treatment decisions are made in the absence of a definite diagnosis. METHODS: In this retrospective study, we assessed the performance of different supervised machine learning algorithms for the early differential diagnosis of candidemia and bacteremia in adult patients on a large dataset automatically extracted within the AUTO-CAND project. RESULTS: Overall, 12,483 episodes of candidemia (1275; 10%) or bacteremia (11,208; 90%) were included in the analysis. A random forest classifier achieved the best diagnostic performance for candidemia, with sensitivity 0.98 and specificity 0.65 on the training set (true skill statistic [TSS] = 0.63) and sensitivity 0.74 and specificity 0.57 on the test set (TSS = 0.31). Then, the random classifier was trained in the subgroup of patients with available serum ß-D-glucan (BDG) and procalcitonin (PCT) values by exploiting the feature ranking learned in the entire dataset. Although no statistically significant differences were observed from the performance measures obtained by employing BDG and PCT alone, the performance measures of the classifier that included the features selected in the entire dataset, plus BDG and PCT, were the highest in most cases. CONCLUSIONS: Random forest classifiers trained on large datasets of automatically extracted data have the potential to improve current diagnostic algorithms for candidemia. However, further development through implementation of automatically extracted clinical features may be necessary to achieve crucial improvements.

Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives.

PURPOSE OF REVIEW: Serious infections caused by nonfermenting Gram-negative bacteria (NF-GNB) pose a significant challenge for clinicians due to the limited treatment options available, which are frequently associated with issues of toxicity and unfavourable pharmacokinetic profiles. The aim of this review is to provide a brief overview of the existing data concerning the ongoing development of antiinfective agents targeting NF-GNB. RECENT FINDINGS: Several agents exhibiting efficacy against NF-GNB are under clinical investigation. Durlobactam-sulbactam and cefepime-taniborbactam emerge as promising therapeutic avenues against carbapenem-resistant Acinetobacter baumanii . Cefepime-zidebactam may serve as a suitable treatment option for urinary tract infections caused by a wide range of NF-GNB. Cefepime-enmetazobactam demonstrates potent in vitro activity against various NF-GNB strains; however, its role as an anti- Pseudomonal agent is inadequately substantiated by available data. Xeruborbactam is a wide ß-lactamase inhibitor that can be associated with a range of agents, enhancing in-vitro activity of these against many NF-GNB, including those resistant to newer, broader spectrum options. Lastly, murepavadin appears to be a potential pathogen-specific solution for severe Pseudomonas infections; however, additional investigation is necessary to establish the safety profile of this compound. SUMMARY: Each of the novel molecules reviewed possesses an interesting range of in-vitro activity against NF-GNB. In addition, some of them have already been proved effective in vivo, underscoring their potential as future treatment options.

Barriers to HCV micro-elimination in a cohort of people living with HIV (PLWH).

To achieve the World Health Organization goal of hepatitis C virus (HCV) eradication, barriers to treatment should be investigated and overcome. The aim of this study was to identify those barriers and describe the strategies adopted to achieve HCV micro-elimination in a cohort of coinfected people living with HIV (PLWH-HCV). Adult PLWH-HCV followed at our hospital with detectable serum HCV-RNA in 2018 were enrolled. After a three-year follow-up, barriers to HCV treatment were investigated and strategies to overcome them were described. Of 492 PLWH-HCV seen in 2018, 29 (5.9%) had detectable serum HCV-RNA. Eight out of 29 (27.6%) were excluded because they were already under treatment, while 2 others were excluded because they moved to other outpatient clinics. Among the remaining 19 study participants, the most common barriers to treatment were poor adherence to therapies and follow-up visits (n=9, 47%), recent HCV diagnosis awaiting proper staging (n=3, 16%) and treatment hesitancy (n=2, 10%). During the following three years, direct-acting antivirals (DAAs) treatment was completed in 11/19 (58%) cases, with achievement of sustained virological response in 100% of cases. For the remaining cases, 2/19 (10.5%) were lost to follow-up, 2/19 (10.5%) died before treatment initiation and 4/19 (21.0%) are still awaiting treatment. Despite 3 years of effort, HCV micro-elimination has not been achieved at our center. We observed that poor adherence and treatment hesitancy were the main barriers to treatment. Strategies addressing these issues need to be implemented.

Management of nonfermenting gram-negative infections: a critique of the guidelines.

PURPOSE OF REVIEW: In the present narrative review, we discuss the characteristics and differences between the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines in terms on their recommendations/suggestions for the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii infections. RECENT FINDINGS: Treatment of severe infections caused by nonfermenting gram-negative bacteria (NF-GNB) is posing both novel hopes and novel challenges to physicians worldwide, and both the IDSA and the ESCMID have recently updated/released their guidelines or guidance documents, based on different philosophies and providing recommendations for the treatment of NF-GNB infections. In order to correctly exploit recent advances in the treatment of such infections, IDSA and ESCMID approaches should be viewed as complementary and evolving, and should not preclude further revision based on accumulating evidence on the use of novel ß-lactams and ß-lactam/ß-lactamase inhibitor combinations. SUMMARY: A joint consideration of both philosophies should leave the door opened for the wise use of novel agents, ultimately building precious experience on their use that could favorably influence future guidelines revisions.