New antimicrobial options for the management of complicated intra-abdominal infections.

Complicated intra-abdominal infections (cIAIs) are a common cause of morbidity and mortality in surgical patients. Optimal management of cIAI requires early source control in combination with adequate antimicrobial treatment and aggressive fluid resuscitation. cIAIs are mainly caused by Gram-negative bacilli and anaerobes. Broad-spectrum single-agent or combination drug regimens against these microorganisms are the mainstay of therapy. However, development of antimicrobial resistance has become an increasingly large concern: multidrug-resistant organisms are associated with a higher rate of inadequate antimicrobial therapy, which in turn is associated with higher mortality rate, longer hospital stay, and increased cost compared to adequate antimicrobial therapy. In this mini-review, we discuss the effectiveness of several new antimicrobial agents, recently approved or in advanced phases of clinical development, for the treatment of cIAIs, including the new beta-lactam and beta-lactamase inhibitor combinations (ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, aztreonam/avibactam), siderophore cephalosporins (cefiderocol), aminoglycosides (plazomicin), and tetracyclines (eravacycline).

Impact of diabetes on the risk of serious liver events and liver-related deaths in people living with HIV and hepatitis C co-infection: data from the ICONA Foundation Cohort Study.

To investigate the association between diabetes and HCV infection in persons living with HIV and to determine the impact of diabetes on the occurrence of serious liver events (SLEs) and liver-related deaths (LRDs) among HIV/HCV-co-infected patients. Patients were included if they had at least one follow-up visit. In a cross-sectional analysis among all HIV patients, we have investigated the association between diabetes and HCV infection. A further longitudinal analysis was performed in the population of HIV/HCV-co-infected free from SLE with FIB-4 index < 3.25 at baseline, using the following endpoints: (A) first event between SLE and LRD; (B) liver fibrosis progression defined as the first of two consecutive FIB-4 > 3.25; (C) first event between SLE, LRD, and liver fibrosis progression. Data from 15,571 HIV patients were analyzed: 2944 (18.9%) were HCV-Ab positive, and 739 (4.7%) presented a diagnosis of diabetes at their last follow-up. Among HIV/HCV-co-infected population, 107 patients had a diagnosis of diabetes. Viremic HCV-co-infected patients had 3-fold risk of diabetes onset than HCV-uninfected patients. On HIV/HCV-co-infected population, 85 SLEs/LRDs occurred over 20,410 person-years of follow-up (PYFU), for an incidence rate of 4.2/1000 PYFU (95%CI 3.4-5.2). Diabetic patients had 3-fold risk of pooled SLE and LRD than patients without diabetes. Furthermore, viremic HCV infection was independently associated with a higher risk of SLE/LRD (aIRR 3.35 [95%CI 1.14-9.83]). In HIV-infected patients, viremic HCV co-infection is a strong predictor of diabetes. Among HIV/HCV-co-infected population, diabetic patients showed an increased risk of SLE/LRD compared with those without diabetes.

Incidence and predictors of single drug discontinuation according to the presence of HCV coinfection in HIV patients from the ICONA Foundation Cohort Study.

To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation. Inverse probability weighting method to control for potential informative censoring was applied. Data from 10,637 patients were analyzed and 1,030 (9.7%) were HCV-Ab positive. Overall, there were 15,464 ART discontinuations due to any reason in 82,415.9 person-years of follow-up (PYFU) for an incidence rate (IR) of 18.8 (95% confidence interval [95%CI] 18.5-19.1) per 100 PYFU. No difference in IR of ART discontinuation due to any reason between HCV-infected and -uninfected patients was found. In a multivariable Poisson regression model, HCV-infected participants were at higher risk of darunavir/r discontinuation due to any reason (adjusted incidence rate ratio = 1.5, 95%CI 1.01-2.22, p value = 0.045) independently of demographics, HIV-related, ART and life-style factors. Among DRV/r treated patients, we found that HCV-viremic patients had twice the risk of ART discontinuation due to any reason than HCV-aviremic patients. In conclusion, HIV/HCV coinfected patients had a marginal risk increase of DRV/r discontinuation due to any reason compared with those without coinfection.

Epidemiology and microbiology of skin and soft tissue infections.

PURPOSE OF REVIEW: Skin and soft tissue infections (SSTIs) are a broad spectrum of diseases, including uncomplicated and complicated infections. Herein, we review the current epidemiology and microbiology of SSTIs. RECENT FINDINGS: In the last decades, a significant growing trend of SSTIs both in the community and healthcare settings with a dramatic increase of the economic burden for these diagnoses was observed. Several observational studies found that SSTIs are a substantial cause of ambulatory and emergency department visits, and of hospitalizations. Although, microbiology of SSTIs changes according to the clinical feature and the severity of illness, Staphylococcus aureus being the leading cause of both uncomplicated infections and complicated infections. Moreover, the increasing prevalence of infections because of multidrug-resistant bacteria, mainly methicillin-resistant S. aureus (both community-acquired and healthcare-associated methicillin-resistant S. aureus), are associated with significantly increased morbidity, mortality, length of hospital stay, and costs, compared with infections because of susceptible strains. Moreover, although it is unclear whether high vancomycin minimum inhibitory concentration is associated with a worse outcome, it poses a further challenge for the clinicians. SUMMARY: The understanding of the current epidemiology and microbiology of SSTIs is indicated for an appropriate antimicrobial therapy and an overall optimal management of SSTIs.

Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.

INTRODUCTION: Enterococci are common causes of infective endocarditis (IE) in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. For decades, cell-wall-active antimicrobial agents (penicillins or vancomycin) in combination with aminoglycosides were the cornerstone of the treatment; however, the emergence of antibiotic resistance has significantly reduced the efficacy of these regimens. MATERIALS AND METHODS: Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. CONCLUSION: New effective and safe combination treatments, including double-ß-lactam and daptomycin/ß-lactam combination, are proving useful for the management of IE due to enterococci.

Pharmacotherapies for multidrug-resistant gram-positive infections: current options and beyond.

INTRODUCTION: Infections due to multidrug-resistant organisms (MDRO) are a serious concern for public health with high morbidity and mortality. Though many antibiotics have been introduced to manage these infections, there are remaining concerns regarding the optimal management of Gram-positive MDROs. AREAS COVERED: A literature search on the PubMed/Medline database was conducted. We applied no language and time limits for the search strategy. In this narrative review, we discuss the current options for managing Gram-positive MDROs as well as non-traditional antibacterial agents in development. EXPERT OPINION: Despite their introduction more than 70 years ago, glycopeptides are still the cornerstone in treating Gram-positive infections: all registrative studies of new antibiotics have glycopeptides as control; these studies are designed as not inferior studies, therefore it is almost impossible to give recommendations other than the use of glycopeptides in the treatment of Gram-positive infections. The best evidence on treatments different from glycopeptides comes from post-hoc analysis and meta-analysis. Non-traditional antibacterial agents are being studied to aid in short and effective antibiotic therapies. The use of non-traditional antibacterial agents is not restricted to replacing traditional antibacterial agents with alternative therapies; instead, they should be used in combination with antibiotic therapies.

Sphingomonas paucimobilis osteomyelitis in an immunocompetent patient. A rare case report and literature review.

Sphingomonas paucimobilis occurs widely both in natural and nosocomial environments, including hospital water systems, respiratory therapy equipment, and laboratory instruments. It is an opportunistic pathogen that rarely causes infections in humans. Among S. paucimobilis nosocomial infections, osteomyelitis is particularly rare. Almost all infections occur in patients with comorbidities such as malignancy, immunosuppressant therapy, diabetes mellitus and acquired immunodeficiency syndrome. We present the first case of Sphingomonas paucimobilis osteomyelitis in an immunocompetent patient and include updated literature concerning infections by this microorganism.

Antibiotic treatment in cirrhotic patients.

In this editorial, we comment on the article by Liakina V: "Antibiotic resistance in patients with liver cirrhosis: Prevalence and current approach to tackle" (World J Clin Cases 2023, 11: 7530-7542). In this excellent review, Liakina presents current data on bacterial complications in patients with cirrhosis. Bacterial infections are the most common complication in patients with liver cirrhosis. We focus specifically on spontaneous bacterial peritonitis (SBP) which is the most representative infectious complication. Liakina V suggested starting empirically, in all patients with suspected SBP, third-generation cephalosporins when the number of polymorphonuclear leukocytes (PMNs) in ascites is greater than 250/mm3. This statement creates some doubts in our clinical practice so we discuss on the unsolved pitfalls of diagnosis and treatment that are often encountered in patients with ascitic fluid infections, especially on bacterascites that is defined as ascitic bacterial growth with PMNs below 250/mm3. The severity of liver disease and overall prognosis are highly comparable for patients with bacterascites and SBP in some recent well-conducted studies. Furthermore, we present a brief analysis of the prevalence of antibiotic-resistant isolates with an introduction of currently approved antibiotic drug options to treat ascitic fluid infections avoiding antibiotic resistance. In light of the most recent epidemiological data, third-generation cephalosporins should not be considered as an empirical antibiotic treatment of choice for ascitic fluid infections.

Burden of severe infections due to carbapenem-resistant pathogens in intensive care unit.

Intensive care units (ICU) for various reasons, including the increasing age of admitted patients, comorbidities, and increasingly complex surgical procedures (e.g., transplants), have become "the epicenter" of nosocomial infections, these are characterized by the presence of multidrug-resistant organisms (MDROs) as the cause of infection. Therefore, the perfect match of fragile patients and MDROs, as the cause of infection, makes ICU mortality very high. Furthermore, carbapenems were considered for years as last-resort antibiotics for the treatment of infections caused by MDROs; unfortunately, nowadays carbapenem resistance, mainly among Gram-negative pathogens, is a matter of the highest concern for worldwide public health. This comprehensive review aims to outline the problem from the intensivist's perspective, focusing on the new definition and epidemiology of the most common carbapenem-resistant MDROs (Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales) to emphasize the importance of the problem that must be permeating clinicians dealing with these diseases.

Antimicrobial approach of abdominal post-surgical infections.

Abdominal surgical site infections (SSIs) are infections that occur after abdominal surgery. They can be superficial, involving the skin tissue only, or more profound, involving deeper skin tissues including organs and implanted materials. Currently, SSIs are large global health problem with an incidence that varies significantly depending on the United Nations' Human Development Index. The purpose of this review is to provide a practical update on the latest available literature on SSIs, focusing on causative pathogens and treatment with an overview of the ongoing studies of new therapeutic strategies.

Outcome of patients with carbapenem-resistant Acinetobacter baumannii infections treated with cefiderocol: A multicenter observational study.

BACKGROUND: No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections. METHODS: We conducted an observational retrospective/prospective multicenter study including all patients> 18 years with carbapenem-resistant A. baumannii (CRAB) infections treated with cefiderocol, from June 12021 to October 30 2022. Primary endpoint was 30-day mortality, secondary end-points the clinical and microbiological response at 7 days and at the end of treatment. Furthermore, we compared the clinical and microbiological outcomes among patients who received cefiderocol in monotherapy or in combination. RESULTS: Thirty-eight patients with forty episodes of infection were included [mean age 65 years (SD+16.3), 75% males, 90% with hospital-acquired infections and 70% showing sepsis or septic shock]. The most common infections included unknown source or catheter-related bacteremia (45%) and pneumonia (40%). We observed at 7 days and at the end of therapy a rate of microbiological failure of 20% and 10%, respectively, and of clinical failure of 47.5% and 32.5%, respectively; the 30-day mortality rate was 47.5%. At multivariate analysis clinical failure at 7 days of treatment was the only independent predictor of 30-day mortality. Comparing monotherapy (used in 72.5%) vs. combination therapy (used in 27.5%), no differences were observed in mortality (51.7 vs 45.5%) and clinical (41.4 vs 63.7%) or microbiological failure (24.1 vs 9.1%). CONCLUSIONS: The findings of this study reinforce the effectiveness of cefiderocol in CRAB infections, also as monotherapy. However, prospective multicenter studies with larger sample sizes and a control group treated with standard of care are needed to identify the best treatment for CRAB infections.

GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

Considerations of antibiotic therapy duration in community- and hospital-acquired bacterial infections.

Despite the large number of suggestions available in the literature, the optimal duration of antibiotic treatment remains an individual decision mainly based on clinical criteria. Shorter but equally effective regimens would reduce the side effect rates, including both antibiotic resistance and drug expenses. Although several prospective, randomized trials and meta-analyses with the aim of comparing a standard duration with a shorter one for most bacterial infections have been published, to date most current recommendations carry little weight, as they are based on expert opinions or practical experience. This review will briefly touch upon the clinical evidence of short-course versus long-course antibiotic therapy for the most common community- and hospital-acquired bacterial infections.

Retrocardiac pneumonia mimicking acute abdomen: a diagnostic challenge.

We present the case of a child who showed acute abdominal pain and fever due to retrocardiac pneumonia by Streptococcus pneumoniae without respiratory signs and symptoms. Acute abdominal pain is a common presenting symptom of children seen in pediatric emergency rooms. Basilar pneumonia is an uncommonly known cause of pediatric abdominal pain; it may go unrecognized on a patient's initial evaluation. Our case suggests that the clinical manifestations of a retrocardiac pneumonia can be atypical with abdominal pain as the principal complaint, mimicking acute abdomen.

A scoping review of retracted publications in anesthesiology.

CONTEXT: Fraudulent publication is a scourge of scientific research. OBJECTIVES: This scoping review was aimed at characterizing retracted publications for fraud or plagiarism in the field of anesthesia. Does the reputation of the journal (Quartile and Impact Factor, IF) protect the reader from the risk of having the manuscript he read withdrawn for fraud/plagiarism? METHODS/DESIGN: This scoping review was planned following the Joanna Briggs Institute recommendations. Data sources: PubMed and the Retraction Watch Database (http://retractiondatabase.org/RetractionSearch.aspx?). Study selection: All types of publications retracted. Data extraction: Year, first author nationality, journal name, journal category, IF, Quartile, H index. Data analysis: The association with Quartile and IF was investigated. RESULTS: No significant association between retraction of papers published in no-Quartile journals and retractions published in journals placed in the highest quartile. CONCLUSIONS: The quality of the surveillance in paper submission is not higher in journals of the first Quartile than in journals not placed in other Quartiles. (The protocol was prospectively registered in the Open Science Framework https://doi.org/10.17605/OSF.IO/TGKNE).

A Descriptive Study on Causes of Death in Hospitalized Patients in an Acute General Hospital of Southern Italy during the Lockdown due to Covid-19 Outbreak.

(1) Background: All deaths that occurred in a hospital of Southern Italy ("San Giuseppe Moscati" Hospital of Avellino) with medium jurisdiction (up to 425,000 citizens approximately) in the period from 9 March to 4 May 2020 were analyzed. The primary endpoint of the study was to analyze the causes of death in the period study. Secondary endpoints included: (1) the assessment of overall mortality in the emergency period compared with the same period of the past years (2018-2019) in the jurisdiction area; (2) the assessment of the amounts of deaths with positive and negative reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal and oropharyngeal swabs; (3) the frequency of clinical and radiological features consistent with Covid-19 infection in negative RT-PCR cases. (2) Methods: Patients' information and laboratory data were collected through the computerized medical record system (My Hospital, Italy) used for the clinical management of all referring patients. Epidemiological, clinical, and radiological data were reviewed along with the results of nasopharyngeal and oropharyngeal swabs. (3) Results: From 9 March to 4 May 2020, 140 deaths (87 males, 53 females) from all causes occurred in total at "San Giuseppe Moscati" Hospital, of which 32 deaths were Covid-19 related. (4) Conclusions: The excess of mortality could be higher than the one reported in the official epidemiological surveys. False negative cases can have a distorting effect on the assessment of the real mortality rate and the excess mortality. Furthermore, many who died from Covid-19 were likely never tested or they had false negative RT-PCR results. Other victims probably died from causes indirectly related to Covid-19.