Navigating the Nexus: HIV and Breast Cancer-A Critical Review.

Despite significant advances in the management of antiretroviral therapy (ART), leading to improved life expectancy for people living with HIV (PLWH), the incidence of non-AIDS-defining cancers, including breast cancer, has emerged as a critical concern. This review synthesizes current evidence on the epidemiology of breast cancer among HIV-infected individuals, highlighting the potential for an altered risk profile, earlier onset, and more advanced disease at diagnosis. It delves into the molecular considerations underpinning the relationship between HIV and breast cancer, including the role of immunosuppression, chronic inflammation, and gene expression alterations. Additionally, it examines the complexities of managing breast cancer in the context of HIV, particularly the challenges posed by ART and anticancer agents' cross-toxicities and drug-drug interactions. The review also addresses survival disparities, underscoring the need for improved cancer care in this population. By identifying gaps in knowledge and areas requiring further research, this review aims to illuminate the complexities of HIV-associated breast cancer, fostering a deeper understanding of its epidemiology, molecular basis, and clinical management challenges, thereby contributing to better outcomes for individuals at the intersection of these two conditions. This narrative review systematically explores the intersection of HIV infection and breast cancer, focusing on the impact of HIV on breast cancer risk, outcomes, and treatment challenges.

Unveiling the Secrets of Acinetobacter baumannii: Resistance, Current Treatments, and Future Innovations.

Acinetobacter baumannii represents a significant concern in nosocomial settings, particularly in critically ill patients who are forced to remain in hospital for extended periods. The challenge of managing and preventing this organism is further compounded by its increasing ability to develop resistance due to its extraordinary genomic plasticity, particularly in response to adverse environmental conditions. Its recognition as a significant public health risk has provided a significant impetus for the identification of new therapeutic approaches and infection control strategies. Indeed, currently used antimicrobial agents are gradually losing their efficacy, neutralized by newer and newer mechanisms of bacterial resistance, especially to carbapenem antibiotics. A deep understanding of the underlying molecular mechanisms is urgently needed to shed light on the properties that allow A. baumannii enormous resilience against standard therapies. Among the most promising alternatives under investigation are the combination sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, xeruborbactam, and the newest molecules such as novel polymyxins or zosurabalpin. Furthermore, the potential of phage therapy, as well as deep learning and artificial intelligence, offer a complementary approach that could be particularly useful in cases where traditional strategies fail. The fight against A. baumannii is not confined to the microcosm of microbiological research or hospital wards; instead, it is a broader public health dilemma that demands a coordinated, global response.

Mortality Attributable to Bloodstream Infections Caused by Different Carbapenem-Resistant Gram-Negative Bacilli: Results From a Nationwide Study in Italy (ALARICO Network).

BACKGROUND: Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). METHODS: Prospective multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales, metallo-ß-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aORs) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. RESULTS: Overall, 1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (P < .001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. CONCLUSIONS: In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.

New generation biologics for the treatment of psoriasis and psoriatic arthritis. State of the art and considerations about the risk of infection.

Psoriasis is a chronic immune-mediated disease characterized by inflammation of skin (psoriasis) or joints (psoriatic arthritis) or both, resulting from a dysregulation in particular of the T helper (Th)17 functions. There is no available cure for psoriasis, and a life-long treatment is needed to control signs and symptoms. Research interest is high around the newest biological drugs approved for the treatment of moderate to severe psoriasis and psoriatic arthritis, and especially drugs blocking the IL-23/IL-17 axis. Our aim is to review the new biological drugs for the treatment of psoriasis and their adverse effects, focusing on the risk of infections.

Malignant melanoma in HIV: Epidemiology, pathogenesis, and management.

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4+ count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience.

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/µL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION: The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.

HIV-associated psoriasis: Epidemiology, pathogenesis, and management.

People living with HIV (PLWH) are affected by a higher incidence skin disorders, which are often associated with high morbidity and mortality. In particular, psoriasis affects PLWH severely and for a longer time than the general population. Human immunodeficiency virus (HIV) infection is characterized by a progressive decrease in CD4+ T-cell count, and it could seem paradoxical that psoriasis exacerbations are more frequent in this subset of patients than the general population, even though it is commonly observed at any stage of infection. For a long time, there have been limited therapeutic choices for PLWH affected by psoriasis. The introduction of the combined antiretroviral therapy dramatically changed the natural course of both HIV and psoriasis in PLWH, leading to an improvement of quality and duration of life. However, the clinical severity of psoriasis in PLWH often requires the use of immunosuppressant drugs. Knowledge about their safety and efficacy are limited to case-reports, small case-series and studies, therefore their use has not yet entered the routine. Further studies are needed to determine if immunosuppressive drugs can be safely and effectively used in PLWH affected by psoriasis and other autoimmune disorders.

Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy.

BACKGROUND: Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014). METHODS: The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods. RESULTS: The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely to show HCV infection alone (48.0% vs. 67.9%). A male preponderance was observed in HBV-related cases (1.99) and in alcoholic-related cases (2.3), a preponderance observed both in the 2001 and in 2014 cases. In HCV-related cases, however, females predominated in 2001 (M/F 0.9) and males in 2014 (M/F 1.5).The rate of cirrhosis in alcohol-related etiology was close to 36% in both genders, a finding much higher than that observed for both sexes in HBV and HCV etiologies.Both males and females enrolled in 2014 were older (p < 0.001) and with a higher rate of cirrhosis and/or HCC (p < 0.001) than those investigated in 2001. There was a remarkable increase over time in the proportion of male abstainers (36.7% in 2001 and 64.3% in 2014). CONCLUSION: This study highlights important inter- and intra-gender differences in the characteristics and etiological factors of patients with CLD in Italy.

Rapid emergence of cryptococcal fungemia, Mycobacterium chelonae vertebral osteomyelitis and gastro intestinal stromal tumor in a young HIV late presenter: a case report.

BACKGROUND: Highly active antiretroviral therapy has significantly changed the natural history of HIV infection, leading to a dramatic reduction of HIV-related morbidity and mortality. Late Presenters, Very Late Presenters and AIDS presenters still represent, also in Europe, including Italy, a huge challenge in terms of diagnostic and therapeutic management. CASE PRESENTATION: A 35-year-old male with a history of fever and back pain. HIV test resulted positive with a high HIV Viral Load and a very low T-CD4 number of cells (5 cells/mm3). Imaging investigations revealed multiple vertebral and pulmonary lesions together with abdominal and thoracic lymphadenopathy. Blood cultures were positive for Cryptococcus neoformans and for Staphylococcus haemolyticus. Lymphnode biopsy resulted positive in PCR for Non-Tuberculosis Mycobacteria (Mycobacterium chelonae). A gastric biopsy also revealed a GIST. The patient also had CMV DNA positive. Although we performed antiretroviral therapy and specific-therapies for each disease, he was transferred to intensive care unit where he died due to an Acute Respiratory Distress Syndrome. CONCLUSION: The reported case is unusual due to the relevant number of opportunistic diseases (both infectious and tumoral) emerging not long after the HIV infection had been diagnosed. Late presenters HIV patients and AIDS presenters still represent a challenge, which is often too complex for clinicians to deal with. In spite of proper management, the risk of suboptimal results cannot be excluded.

Hepatitis delta infection in Italian patients: towards the end of the story?

BACKGROUND: The endemicity of hepatitis delta virus infection in Italy has decreased in the last decades. AIM: To evaluate the current epidemiology of chronic delta infection in Italy and to compare the present findings with the corresponding figures from the previous studies. METHODS: A cross-sectional study involving 16 referral centres scattered all over the country in 2014. RESULTS: Out of the 513 hepatitis B surface antigen-positive subjects enrolled, 61 (11.9%) were anti-delta positive, with a sex ratio (M/F) of 2.05. The majority (80.3%) of them was 50 years or older, while the proportion of subjects younger than 30 years of age was as low as 3.3%. No difference was detected by geographical area of residence. The presence of liver cirrhosis was diagnosed in 52.4% of cases. In comparison to previous studies, a further shift towards the oldest age groups and an increasing proportion of subjects having liver cirrhosis among all anti-delta-positive subjects are observed. CONCLUSIONS: Currently, hepatitis delta infection mostly affects old people who have an advanced but indolent liver disease, reflecting a survival effect. The defective hepatitis delta virus is near to disappear in the country, where it has been discovered in the second half of 70s.

Heel quantitative ultrasound in HIV-infected patients: a cross-sectional study.

PURPOSE: HIV infection has been associated with increased risk of osteoporosis and fragility fractures. Dual-energy X-ray absorptiometry (DXA) is the reference standard to assess bone mineral density (BMD); however, it is not easily accessible in several settings. Heel Quantitative ultrasound (QUS) is a radiation-free, easy-to-perform technique, which may help reducing the need for DXA. METHODS: In this cross-sectional study, we used heel QUS (Hologic Sahara(®)) to assess bone status in a cohort of HIV-infected patients. A QUS stiffness index (QUI) threshold >83 was used to identify patients with a low likelihood of osteoporosis. Moreover, we compared QUS results with those of 36 sex- and age-matched HIV-negative controls. RESULTS: 244 HIV-positive patients were enrolled. Median heel QUI value was 83 (73-96) vs. 93 (IQR 84-104) in the control group (p = 0.04). 110 patients (45 %) had a QUI value ≤83. Risk factors for low QUI values were age (OR 1.04 per year, 95 % CI 1.01-1.07, p = 0.004), current use of protease inhibitors (OR 1.85, CI 1.03-3.35, p = 0.039), current use of tenofovir (OR 2.28, CI 1.22-4.27, p = 0.009) and the number of risk factors for secondary osteoporosis (OR 1.46, CI 1.09-1.95, p = 0.01). Of note, QUI values were significantly correlated with FRAX score (r = -0.22, p = 0.004). According to EACS guidelines, 45 % of patients had risk factors for osteoporosis which make them eligible for DXA. By using QUS, we may avoid DXA in around half of them. CONCLUSIONS: As HIV-positive patients are living longer, the prevalence of osteoporosis is expected to increase over time. Appropriate screening, prevention and treatment are crucial to preserve bone health in this population. The use of screening techniques, such as heel QUS, may help reducing the need for DXA. Further studies are needed to define the diagnostic accuracy of this promising technique in the setting of HIV.

Chronic HBV infection in pregnant immigrants: a multicenter study of the Italian Society of Infectious and Tropical Diseases.

The aims of the study were to estimate the clinical impact of HBV infection in pregnant immigrants and their family members and to identify a useful approach to managing the healthcare of HBsAg-positive immigrants. Included in this study were 143 HBsAg-positive pregnant immigrants of the 1,970 from countries with intermediate/high HBV endemicity who delivered in 8 Italian hospitals in 2012-2013. In addition, 172 family members of 96 HBsAg-positive pregnant immigrants were tested for serum HBsAg. The median age of the 143 HBsAg-positive pregnant immigrants was 31.0±12.1 years and the length of stay in Italy 5.0±4.1 years; 56.5% were unaware of their HBsAg positivity. HBV DNA was detected in 74.5% of the pregnant immigrants, i.e., 94.3% from Eastern Europe, 72.2% from East Asia and 58.1% from Sub-Saharan Africa. HBV DNA ≥2000 IU/mL was detected in 47.8% of pregnant immigrants, associated with ALT ≥1.5 times the upper normal value in 15% of cases. Anti-HDV was detected in 10% of cases. HBsAg was detected in 31.3% of the 172 family members. All HBsAg-positive immigrants received counseling on HBV infection and its prevention, and underwent a complete clinical evaluation. The findings validate the approach used for the healthcare management of the HBsAg-positive immigrant population.

Duration of antimicrobial therapy in community acquired pneumonia: less is more.

Community acquired pneumonia (CAP) represents the most common cause of infection-related morbidity and mortality worldwide. Appropriate treatment of CAP is challenging and sometimes limited by the availability to obtain rapid and timely identification of the etiologic agent in order to initiate or deescalate the correct antimicrobial therapy. As a consequence, prescribers frequently select empiric antimicrobial therapy using clinical judgment, local patterns of antimicrobial resistance, and, sometimes, individual patient expectations. These issues may contribute to prolonged courses of inappropriate therapy. In this review, we discuss the evidence and recommendations from international guidelines for the management of CAP and the clinical trials that specifically addressed duration of antimicrobial therapy for CAP in adults. In randomized controlled trials comparing the clinical efficacy of a short-course antimicrobial regimen versus an extended-course regimen, no differences in terms of clinical success, bacterial eradication, adverse events, and mortality were observed. The use of biomarkers, such as procalcitonin, to guide the initiation and duration of antimicrobial therapy may reduce total antibiotic exposure and treatment duration, healthcare costs, and the risk of developing antimicrobial resistance. In clinical practice, antimicrobial stewardship interventions may improve the management of CAP and may help in reducing treatment duration. Sometimes "less is more" in CAP.

Use of Cefiderocol in Adult Patients: Descriptive Analysis from a Prospective, Multicenter, Cohort Study.

INTRODUCTION: Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. METHODS: In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. RESULTS: Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01-6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05-72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16-0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-ß-lactamase producers, respectively. CONCLUSIONS: Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Sorafenib for the treatment of unresectable hepatocellular carcinoma in HIV-positive patients.

Few data are available on the safety and efficacy of sorafenib in HIV-infected patients with unresectable hepatocellular carcinoma (HIV-u-HCC) and concomitant highly active antiretroviral therapy (HAART). Between July 2007 and October 2010, 27 consecutive HIV-u-HCC patients were treated with sorafenib and concomitant HAART within the Gruppo Italiano Cooperativo AIDS e Tumori (GICAT). Three patients achieved a partial response, 12 achieved a stable disease, and 12 showed progression. The median time to progression and overall survival was 5.1 (range 0.5-13.3) and 12.8 (range 1.1-23.5) months, respectively. Grades 3-4 toxicities included diarrhea (four patients, 14.8%), hypertension (three patients, 11%), and hand-and-foot skin reaction (four patients, 14.9%). Most drug-related side effects were low grade and manageable. This retrospective study shows favorable survival data among HIV-u-HCC patients treated with sorafenib together with a reasonable safety profile.

Interferon-γ and interleukin-17 production from PPD-stimulated PBMCss of patients with pulmonary tuberculosis.

PURPOSE: The purpose of this study was to evaluate Interferon (IFN)-γ and Interleukin(IL)-17 profiles in patients with different clinical presentations of pulmonary tuberculosis (TB) and to compare them with those of tuberculin-negative and tuberculin-reactive healthy controls METHODS: Peripheral blood mononuclear cells (PBMCss), isolated from patients (n=52) and controls (n=30), were stimulated ex vivo with purified protein derivative (PPD) and IFN-γ and IL-17 levels in the supernatant were measured. RESULTS: At baseline, PBMCss from patients with TB released a significantly lower amount of IL-17 (p=0.043) than PBMCss from healthy controls, whereas IFN-γ levels were similar in the two groups. After PPD stimulation, a significant rise in IL-17 levels was found only among healthy controls (p=0.02). This rise in IL-17 levels was similar between tuberculin-reactive and tuberculin-negative subjects. After PPD stimulation, patients with infiltrative TB secreted higher levels of IL-17 and IFN-γ than those affected with chronic, miliary and cavitary TB (p < 0.01). IFN-γ production from patients with infiltrative TB was even higher than for healthy controls (p < 0.01). PBMCss from tuberculin-reactive patients released higher levels of IFN-γ than tuberculin-negative subjects after PPD stimulation (p < 0.01). CONCLUSION: Ex vivo PPD stimulation of PBMCs from patients with pulmonary TB does not significantly stimulate IL-17 release; however, higher IL-17 and IFN-γ levels are found in patients with infiltrative disease, in comparison with those affected with miliary, cavitary and chronic TB.

Localized and systemic bacterial infections in necrotizing pancreatitis submitted to surgical necrosectomy or percutaneous drainage of necrotic secretions.

BACKGROUND: Infectious complications are observed in 40-70% of all patients with severe acute pancreatitis. Infections are associated with a significant increase in mortality rates. METHODS: We evaluated the prevalence and characteristics of pancreatic and systemic infections in 46 patients with necrotizing pancreatitis submitted to surgical procedures during their hospital stay as well as the impact of such infectious complications on patient clinical outcome. Samples for microbiological cultures were taken at hospital admission from blood and bile and 2 days after invasive procedure from blood, drainage fluid, bile and necrotic tissues. RESULTS: 74% patients with necrotizing pancreatitis had a localized or systemic infection. At admission, 15% of subjects had positive blood cultures whereas 13% had evidence of bacterial growth from bile cultures. Two days after the invasive procedures for removal of necrotic materials and fluids, blood cultures became positive in 30% of patients in spite of antibiotic prophylaxis and bile cultures resulted positive in 22% of cases. Furthermore, bacterial growth from drainage fluids was found in 30% and from homogenized necrotic material in 44% of cases. As refers to bacterial isolates, all patients had a monomicrobial infection. Carbapenems were the drugs with the best sensitivity profile. CONCLUSIONS: Infectious complications significantly increase mortality in patients with necrotizing pancreatitis. In addition, subjects with systemic infections developed more complications and demonstrated a higher mortality rate in comparison with those having a localized infection. In our study, the sensitivity pattern of the isolated microorganisms suggests to consider carbapenems as the best option for empirical treatment in patients with necrotizing pancreatitis who develop a clear-cut evidence of systemic or localized bacterial infection.

Mucorales/Fusarium Mixed Infection in Hematologic Patient with COVID-19 Complications: An Unfortunate Combination.

Hematological diseases, especially those causing severe neutropenia, represent the main factor in the development of invasive fungal infections (IFIs). Furthermore, COVID-19 has been considerably associated with IFIs due to immunological dysregulation, prolonged hospitalization in intensive care units, and immunomodulatory therapies. Opportunistic molds are correlated with elevated morbidity and mortality rates in these patients, due to immune impairment, diagnostic complexity, and therapeutic challenges. Among opportunistic fungal infections, the Mucorales and Fusarium species are considered particularly aggressive, especially during severe neutropenia. A mixed Mucorales/Fusarium infection has been rarely described in scientific literature. Herein, we report a case of Mucorales and Fusarium co-infection in a patient with acute leukemia whose clinical history was also complicated by COVID-19. Herein, we report a challenging case in order to encourage the clinical suspicion of combined fungal infections in immunosuppressed patients, performing a punctual microbiological diagnosis, and promptly administering the correct empiric and targeted antifungal therapy.

Ceftazidime-Avibactam Treatment for Klebsiella pneumoniae Bacteremia in Preterm Infants in NICU: A Clinical Experience.

Ceftazidime/avibactam (CAZ/AVI) is an antibiotic combination approved for the treatment of several infections caused by multi-drug resistant (MDR) Gram-negative bacteria. Neonates admitted to the Neonatal Intensive Care Unit (NICU) are at high risk of developing bacterial infections, and the choice of appropriate antibiotics is crucial. However, the use of antibiotics in neonates carries risks such as antibiotic resistance and disruption of gut microbiota. This study aimed to assess the safety and efficacy of CAZ/AVI in preterm infants admitted to the NICU. Retrospective data from preterm infants with Klebsiella pneumoniae bacteremia who received CAZ/AVI were analyzed. Clinical and microbiological responses, adverse events, and outcomes were evaluated. Eight patients were included in the study, all of whom showed clinical improvement and achieved microbiological cure with CAZ/AVI treatment. No adverse drug reactions were reported. Previous antibiotic therapies failed to improve the neonates' condition, and CAZ/AVI was initiated based on clinical deterioration and epidemiological considerations. The median duration of CAZ/AVI treatment was 14 days, and combination therapy with fosfomycin or amikacin was administered. Previous case reports have also shown positive outcomes with CAZ/AVI in neonates. However, larger trials are needed to further investigate the safety and efficacy of CAZ/AVI in this population.