Sepsis Outcome after Major Abdominal Surgery Does Not Seem to Be Improved by the Use of Pentameric Immunoglobulin IgM: A Single-Center Retrospective Analysis.

BACKGROUND: Sepsis still represents a major public health issue worldwide, and the immune system plays a main role during infections; therefore, its activity is mandatory to resolve this clinical condition. In this report, we aimed to retrospectively verify in a real-life setting the possible usefulness of pentameric IgM plus antibiotics in recovering patients with sepsis after major abdominal surgery. MATERIALS/METHODS: We reviewed, from January 2013 until December 2019, all adult patients admitted to the ICU for sepsis or septic shock (2) after major abdominal surgery. Among these patients, were identified those that, according to legal indication and licenses in Italy, were treated with pentameric IgM plus antibiotics (Group A) or with antibiotics alone (Group B). The following parameters were evaluated: blood gas analysis, lactate, CRP, procalcitonin, endotoxin activity, liver and renal function, coagulation and blood cell count at different time points (every 48 h for at least 7 days). Differences between groups were analyzed using Fisher's exact test or a chi-square test for categorical variables. A Mann-Whitney U test or Kruskal-Wallis test were instead been performed to compare continuous variables. Univariate and multivariate analysis were also performed. RESULTS: Over a period of 30 months, 24 patients were enrolled in Group A and 20 patients in Group B. In those subjects, no statistical differences were found in terms of bacterial or fungal infection isolates, when detected in a blood culture test, or according to inflammatory index, a score, lactate levels and mortality rate. A 48 h response was statistically more frequent in Group B than in Group A, while no differences were found in other clinical and laboratory evaluations. CONCLUSIONS: Based on our results, the use of pentameric IgM does not seem to give any clinical advantages in preventing sepsis after major abdominal surgery.

Hypernatremia During Intravenous Treatment With Fosfomycin: A Retrospective Medical Record Review Study and an Analysis of Spontaneous Reports in the EudraVigilance Database.

Background: Hypernatremia is a serious event that can occur during intravenous (IV) treatment with fosfomycin, and it can also be caused by a wrong drug preparation. Considering the clinical significance of hypernatremia, we decided to carry out two studies by using two different data sources with the aim to evaluate cases of IV fosfomycin-induced hypernatremia. Methods: A retrospective medical record review was performed from June 2017 to June 2019 using data from two hospitals in Southern Italy. The information collected was related to the patients, the antibiotic treatment regimen, type of adverse drug reaction (ADR), hypernatremia severity classification, and drug withdrawal due to ADRs. Moreover, a pharmacovigilance study was performed from the date of the European marketing authorization of fosfomycin to October 11, 2021, using data reported on the European website of suspected ADRs. Information related to the patient characteristics, treatment, hypernatremia, and type of reporter was retrieved. Results: From the retrospective medical record review, a total of 62 patients (48 men and 14 women) in treatment with fosfomycin were identified, of which 17 experienced ADRs. Specifically, 11 patients experienced hypernatremia. During the period from June 2017 to June 2018, a total of 63.7% of hypernatremia events were related to the wrong reconstitution of the drug. According to these results, a surveillance and training campaign about the correct drug reconstitution was managed. However, from June 2018 to June 2019, we still had four new hypernatremia cases. Drug withdrawal occurred in only one patient with hypernatremia. From the pharmacovigilance study, a total of 25 cases of IV fosfomycin-induced hypernatremia were retrieved. No substantial difference was found for patients' distribution by sex. Most cases were classified as serious (68%) and reported "Recovered/resolved" as the outcome (44%). In the majority of cases, fosfomycin was the only suspected drug reported (72%). Conclusion: Our results show that training campaigns on the correct drug preparation need to be strengthened to allow a reduction of hypernatremia cases. Moreover, when close monitoring and management is performed by the infectious disease (ID) specialist and hospital pharmacist, there also is a reduction in antibiotic withdrawal due to hypernatremia.

A survey on antibiotic therapy knowledge among physicians of a tertiary care and university hospital.

Antibiotic therapy has resulted in major progress in the fight against infectious diseases and is associated with an improved quality of life and increased survival. However, the emergence of resistant bacterial strains represents an inevitable consequence of antibiotic treatment and yields a loss of beneficial effects. Due to the scarce availability of new molecules in the near future, physicians have to learn how to best use currently available molecules. The aim of the present study was to evaluate the criteria that physicians use in choosing targeted antibiotic therapy. To achieve this goal, we used a questionnaire comprising seven questions. The questionnaire was administered, with the guarantee of anonymity, to a pool of physicians at the Federico II University Hospital of Naples who could prescribe antibiotics. Of the physicians interviewed, 68% chose antibiotic therapy autonomously or in cooperation with other doctors of the same structure, whereas 30% of interviewees referred to the infectious diseases consultant (8% after the first bacterial isolation and 22% after antibiotic therapy failure). The definition and meaning of minimum inhibitory concentration (MIC) were known to the vast majority of physicians (82% and 83%, respectively). In contrast, few of the interviewees knew the definition or meaning of breakpoint (16% and 17%, respectively). The key question of the questionnaire focused on the main criterion for antibiotic choice: 68% of interviewees gave an incorrect answer, most interviewees considering only the lowest MIC value for the isolated bacterium as the fundamental parameter in antibiotic choice. Our study shows that antibiotic therapy in a teaching hospital is often chosen using inappropriate criteria. Due to the well-known effects of the wrong antibiotic choice on therapeutic failure rate and on healthcare cost, information and training programmes for physicians who prescribe antibiotics are urgently needed.

Asunaprevir, a protease inhibitor for the treatment of hepatitis C infection.

According to the World Health Organization, approximately 150 million people worldwide are chronic carriers of hepatitis C virus (HCV). HCV infection can evolve into cirrhosis of the liver and its complications, which are ultimately responsible for more than 350,000 deaths every year. Antiviral therapy, when successful, is able to decrease the rate of progression and increase survival. Two types of therapies are currently available, ie, interferon-based therapies and interferon-free ones. The latter have several advantages in terms of safety and tolerability, and could be used even in the most advanced stages of the disease. However, their use is restricted to some viral genotypes (genotype 2 and 3) and they are expensive. Several molecules are in an advanced phase of development. This review deals with the pharmacokinetics, pharmacodynamics, tolerability, and safety of asunaprevir, an inhibitor of HCV nonstructural 3 protease. Asunaprevir exerts optimal in vitro activity particularly against HCV genotypes 1 and 4, and its pharmacokinetic profile enables twice daily administration. The drawback of asunaprevir, and of all protease inhibitors, is its low barrier to resistance. Consequently, it is used in association with other drugs to prevent resistance. Specifically, when combined with daclatasvir, an NS5A inhibitor, asunaprevir results in a very high rate of viral eradication in both treatment-naïve and treatment-experienced patients, with a sustained virological response rate of 80%-90%. Tolerability is fair; in fact, asunaprevir is associated with a transient increase in aminotransferase levels, which is mild in most cases. In conclusion, asunaprevir is a good candidate component of interferon-free combinations and may revolutionize the treatment of chronic HCV infection in the near future.

A retrospective study on HIV and syphilis.

In the early 1990s a reduction in the rate of sexually transmitted infections (STIs) occurred, although recent years have seen an increase. The aim of this study was to examine epidemiological and clinical features of syphilis cases in patients with HIV infection. We reviewed the charts of HIV-infected patients referring to our centre in the period 2002-2011. Fifty of the 402 consecutive HIV-positive patients (12.4%) received a diagnosis of syphilis. An increasing trend in the number of syphilis cases was observed within the period of the study. Most patients with syphilis (64%) presented a latent syphilis of unknown duration. About half of these received a concomitant diagnosis of HIV infection. Men who have sex with men (MSM) were the largest group. In the years 2002-2011, the incidence of syphilis in HIV-infected patients increased in our centre, notably among MSM. There is an urgent need for campaigns aiming to prevent STIs.

Human platelet antigen-3 genotype predicts platelet count in patients with HCV infection.

BACKGROUND/AIM: A low platelet count is one of the most sensitive tests for cirrhosis detection in patients with hepatitis C virus (HCV) infection. We evaluated whether the human platelet antigen (HPA) genotype could predict platelet count in HCV-positive patients. MATERIALS AND METHODS: We genotyped the HPA 1, 2, 3, 5 and 15 polymorphisms in consecutive patients with HCV infection. RESULTS: Out of the 56 patients enrolled, 56.1% had liver cirrhosis. The mean platelet count was significantly lower in those with HPA1aa genotype than in those with HPA1ab/bb genotype. Platelet count did not differ among the other HPA polymorphisms. However, at logistic regression analysis, only the HPA3aa genotype and liver cirrhosis were independent predictors of a low platelet count. CONCLUSION: HPA3aa is an independent factor for a low platelet count in this cohort of patients with HCV chronic infection regardless of disease stage.

Resolution of autoimmune thrombocytopenia associated with raltegravir use in an HIV-positive patient.

About 10% of the human immunodeficiency virus (HIV) patients show thrombocytopenia. We describe the case of an HIV/HCV-positive patient whose autoimmune thrombocytopenia resolved with the addition of raltegravir to previous highly active antiretroviral therapy (HAART). It is noteworthy that the effect on platelet count appeared to be independent of viral load suppression, which was achieved with previous antiretroviral regimens. In fact, it has been suggested that the positive effect exerted by raltegravir on autoimmune diseases is due to its inhibition on herpes viruses, and hence on activation of endogenous human retroviruses. This consideration, if confirmed, could open new avenues in the treatment of autoimmune thrombocytopenia in the HIV setting.