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Antibiotics (Basel, Switzerland) Dec 2023This comprehensive review aims to provide a practical guide for intensivists, focusing on enhancing patient care associated with nosocomial peritonitis (NP). It explores... (Review)
Review
This comprehensive review aims to provide a practical guide for intensivists, focusing on enhancing patient care associated with nosocomial peritonitis (NP). It explores the epidemiology, diagnosis, and management of NP, a significant contributor to the mortality of surgical patients worldwide. NP is, per definition, a hospital-acquired condition and a consequence of gastrointestinal surgery or a complication of other diseases. NP, one of the most prevalent causes of sepsis in surgical Intensive Care Units (ICUs), is often associated with multi-drug resistant (MDR) bacteria and high mortality rates. Early clinical suspicion and the utilization of various diagnostic tools like biomarkers and imaging are of great importance. Microbiology is often complex, with antimicrobial resistance escalating in many parts of the world. Fungal peritonitis and its risk factors, diagnostic hurdles, and effective management approaches are particularly relevant in patients with NP. Contemporary antimicrobial strategies for treating NP are discussed, including drug resistance challenges and empirical antibiotic regimens. The importance of source control in intra-abdominal infection management, including surgical and non-surgical interventions, is also emphasized. A deeper exploration into the role of open abdomen treatment as a potential option for selected patients is proposed, indicating an area for further investigation. This review underscores the need for more research to advance the best treatment strategies for NP.
PubMed: 38136745
DOI: 10.3390/antibiotics12121711 -
Pediatric Radiology Aug 2023Tuberculosis (TB) remains one of the major public health threats worldwide, despite improved diagnostic and therapeutic methods. Tuberculosis is one of the main causes... (Review)
Review
Tuberculosis (TB) remains one of the major public health threats worldwide, despite improved diagnostic and therapeutic methods. Tuberculosis is one of the main causes of infectious disease in the chest and is associated with substantial morbidity and mortality in paediatric populations, particularly in low- and middle-income countries. Due to the difficulty in obtaining microbiological confirmation of pulmonary TB in children, diagnosis often relies on a combination of clinical and radiological findings. The early diagnosis of central nervous system TB is challenging with presumptive diagnosis heavily reliant on imaging. Brain infection can present as a diffuse exudative basal leptomeningitis or as localised disease (tuberculoma, abscess, cerebritis). Spinal TB may present as radiculomyelitis, spinal tuberculoma or abscess or epidural phlegmon. Musculoskeletal manifestation accounts for 10% of extrapulmonary presentations but is easily overlooked with its insidious clinical course and non-specific imaging findings. Common musculoskeletal manifestations of TB include spondylitis, arthritis and osteomyelitis, while tenosynovitis and bursitis are less common. Abdominal TB presents with a triad of pain, fever and weight loss. Abdominal TB may occur in various forms, as tuberculous lymphadenopathy or peritoneal, gastrointestinal or visceral TB. Chest radiographs should be performed, as approximately 15% to 25% of children with abdominal TB have concomitant pulmonary infection. Urogenital TB is rare in children. This article will review the classic radiological findings in childhood TB in each of the major systems in order of clinical prevalence, namely chest, central nervous system, spine, musculoskeletal, abdomen and genitourinary system.
Topics: Child; Humans; Abscess; Tuberculosis, Central Nervous System; Tuberculoma; Diagnostic Imaging; Tuberculosis, Lymph Node
PubMed: 37217783
DOI: 10.1007/s00247-023-05648-z -
Journal of Feline Medicine and Surgery Sep 2023Feline infectious peritonitis (FIP) is a serious disease that arises due to feline coronavirus infection. The nucleoside analogues remdesivir and GS-441524 can be...
Retrospective study and outcome of 307 cats with feline infectious peritonitis treated with legally sourced veterinary compounded preparations of remdesivir and GS-441524 (2020-2022).
OBJECTIVES
Feline infectious peritonitis (FIP) is a serious disease that arises due to feline coronavirus infection. The nucleoside analogues remdesivir and GS-441524 can be effective in its treatment, but most studies have used unregulated products of unknown composition. The aim of the present study was to describe the treatment of FIP using legally sourced veterinary-prescribed regulated veterinary compounded products containing known amounts of remdesivir (injectable) or GS-441524 (oral tablets).
METHODS
Cats were recruited via email advice services, product sales contacts and study publicity. Cats were excluded if they were deemed unlikely to have FIP, were not treated exclusively with the veterinary compounded products, or if there was a lack of cat and/or treatment (including response) data. Extensive cat and treatment data were collected.
RESULTS
Among the 307 cats recruited, the predominant type of FIP was most commonly abdominal effusive (49.5%) and then neurological (14.3%). Three treatment protocols were used; remdesivir alone (33.9%), remdesivir followed by GS-441524 (55.7%) and GS-441524 alone (10.4%). The median (range) initial treatment period duration and longest follow-up time point after starting treatment were 84 (1-330) days and 248 (1-814) days, respectively. The most common side effect was injection pain (in 47.8% of those given subcutaneous remdesivir). Of the 307 cats, 33 (10.8%) relapsed, 15 (45.5%) during and 18 (54.5%) after the initial treatment period. At the longest follow-up time point after completion of the initial treatment period, 84.4% of cats were alive. The cats achieving a complete response within 30 days of starting treatment were significantly more likely to be alive at the end of the initial treatment period than those cats that did not.
CONCLUSIONS AND RELEVANCE
Legally sourced remdesivir and GS-441524 products, either alone or used sequentially, were very effective in the treatment of FIP in this group of cats. Variable protocols precluded statistical comparison of treatment regimens.
Topics: Cats; Animals; Retrospective Studies; Feline Infectious Peritonitis; Coronavirus Infections; Cat Diseases
PubMed: 37732386
DOI: 10.1177/1098612X231194460 -
EBioMedicine Mar 2024Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene...
BACKGROUND
Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) and its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, and inflammation in macrophages. Here we explore whether itaconate regulates phagocytosis.
METHODS
Phagocytosis of macrophages was investigated by time-lapse video recording, flow cytometry, and immunofluorescence staining in macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing and ChIP-sequencing assays were used to explore the underlying mechanisms. The effects of Irg1/itaconate axis on the prognosis of intracerebral hemorrhagic stroke (ICH) and peritonitis was observed in transgenic (Irg1; Cx3cr1, cKO) mice or control mice in vivo.
FINDINGS
In a mouse model of ICH, depletion of Irg1 in macrophage/microglia decreased its phagocytosis of erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p < 0.05). Administration of sodium itaconate/4-octyl itaconate (4-OI) promoted macrophage phagocytosis (n = 7 animals/group, p < 0.05). In addition, in a mouse model of peritonitis, Irg1 deficiency in macrophages also inhibited phagocytosis of Staphylococcus aureus (n = 5 animals/group, p < 0.05) and aggravated outcomes (n = 9 animals/group, p < 0.05). Mechanistically, 4-OI alkylated cysteine 155 on the Kelch-like ECH-associated protein 1 (Keap1), consequent in nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and transcriptional activation of Cd36 gene. Blocking the function of CD36 completely abolished the phagocytosis-promoting effects of Irg1/itaconate axis in vitro and in vivo.
INTERPRETATION
Our findings provide a potential therapeutic target for phagocytosis-deficiency disorders, supporting further development towards clinical application for the benefit of stroke and peritonitis patients.
FUNDING
The National Natural Science Foundation of China (32070735, 82371321 to Q. Li, 82271240 to F. Yang) and the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ202010025033 to Q. Li).
Topics: Humans; Mice; Animals; Kelch-Like ECH-Associated Protein 1; Hemorrhagic Stroke; NF-E2-Related Factor 2; Macrophages; Peritonitis; Phagocytosis; Prognosis; Hydro-Lyases; Succinates
PubMed: 38324982
DOI: 10.1016/j.ebiom.2024.104993 -
Cureus Jul 2023Peritoneal adhesions form as a result of trauma to the abdomen, injuries resulting from surgery, and infections. These tissutal neoformations are innervated and... (Review)
Review
Peritoneal adhesions form as a result of trauma to the abdomen, injuries resulting from surgery, and infections. These tissutal neoformations are innervated and vascularized, and with lymphatic vessels, adherence becomes a new and independent structure, capable of negatively influencing visceral functions. Adherent neogenesis can be asymptomatic or can be a source of pain, limiting the patient's quality of life. Although adhesiolysis remains the elective approach to eliminate adhesions, this therapeutic route prepares the peritoneal anatomical area to recur. The article reviews information on adhesion formation and peritoneal anatomy, probable subjective predispositions, and pathways that carry nociception. The text aims to be a theoretical basis for making new treatment suggestions for non-invasive osteopathic medicine, through a second part will be discussed in another article.
PubMed: 37502471
DOI: 10.7759/cureus.42472 -
Cell Reports. Medicine Jul 2023During differentiation, neutrophils undergo a spontaneous pro-inflammatory program that is hypothesized here to be under caspase-8 control. In mice, intraperitoneal...
During differentiation, neutrophils undergo a spontaneous pro-inflammatory program that is hypothesized here to be under caspase-8 control. In mice, intraperitoneal administration of the caspase-8 inhibitor z-IETD-fmk is sufficient to unleash the production of pro-inflammatory cytokines and neutrophil influx in the absence of cell death. These effects are due to selective inhibition of caspase-8 and require tonic interferon-β (IFN-β) production and RIPK3 but not MLKL, the essential downstream executioner of necroptotic cell death. In vitro, stimulation with z-IETD-fmk is sufficient to induce significant cytokine production in murine neutrophils but not in macrophages. Therapeutic administration of z-IETD-fmk improves clinical outcome in models of lethal bacterial peritonitis and pneumonia by augmenting cytokine release, neutrophil influx, and bacterial clearance. Moreover, the inhibitor protects mice against high-dose endotoxin shock. Collectively, our data unveil a RIPK3- and IFN-β-dependent pathway that is constitutively activated in neutrophils and can be harnessed therapeutically using caspase-8 inhibition.
Topics: Animals; Mice; Apoptosis; Bacterial Infections; Caspase 8; Cytokines; Neutrophil Activation
PubMed: 37390829
DOI: 10.1016/j.xcrm.2023.101098 -
PLoS Pathogens Oct 2023Even though gammaherpesvirus and parasitic infections are endemic in parts of the world, there is a lack of understanding about the outcome of coinfection. In humans,...
Even though gammaherpesvirus and parasitic infections are endemic in parts of the world, there is a lack of understanding about the outcome of coinfection. In humans, coinfections usually occur sequentially, with fluctuating order and timing in different hosts. However, experimental studies in mice generally do not address the variables of order and timing of coinfections. We sought to examine the variable of coinfection order in a system of gammaherpesvirus-helminth coinfection. Our previous work demonstrated that infection with the intestinal parasite, Heligmosomoides polygyrus, induced transient reactivation from latency of murine gammaherpesvirus-68 (MHV68). In this report, we reverse the order of coinfection, infecting with H. polygyrus first, followed by MHV68, and examined the effects of preexisting parasite infection on MHV68 acute and latent infection. We found that preexisting parasite infection increased the propensity of MHV68 to reactivate from latency. However, when we examined the mechanism for reactivation, we found that preexisting parasite infection increased the ability of MHV68 to reactivate in a vitamin A dependent manner, a distinct mechanism to what we found previously with parasite-induced reactivation after latency establishment. We determined that H. polygyrus infection increased both acute and latent MHV68 infection in a population of tissue resident macrophages, called large peritoneal macrophages. We demonstrate that this population of macrophages and vitamin A are required for increased acute and latent infection during parasite coinfection.
Topics: Humans; Animals; Mice; Virus Activation; Coinfection; Virus Latency; Vitamin A; B-Lymphocytes; Herpesviridae Infections; Gammaherpesvirinae; Macrophages; Latent Infection; Helminths; Parasitic Diseases; Mice, Inbred C57BL
PubMed: 37847677
DOI: 10.1371/journal.ppat.1011691 -
Medizinische Klinik, Intensivmedizin... Nov 2023Because 8-10% of children in the emergency room present with acute abdominal pain, a systematic work-up is essential to rule out acute abdomen. (Review)
Review
BACKGROUND
Because 8-10% of children in the emergency room present with acute abdominal pain, a systematic work-up is essential to rule out acute abdomen.
OBJECTIVES
This article highlights the etiology, symptoms, diagnostic workup, and treatment of acute abdomen in children.
MATERIALS AND METHODS
Review of the current literature.
RESULTS
Abdominal inflammation, ischemia, bowel and ureteral obstruction, or abdominal bleeding are causes of acute abdomen. Extra-abdominal diseases such as otitis media in toddlers or testicular torsion in adolescent boys can also lead to symptoms of acute abdomen. Abdominal pain, (bilious) vomiting, abdominal guarding, constipation, blood-tinged stools, abdominal bruise marks, and poor condition of the patient with symptoms such as tachycardia, tachypnea, and hypotonia up to shock are leading symptoms of acute abdomen. In some cases, emergent abdominal surgery is needed to treat the cause of the acute abdomen. However, in patients with pediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV‑2 infection (PIMS-TS), a new disease causing an acute abdomen, surgical treatment is rarely needed.
CONCLUSIONS
Acute abdomen can lead to nonreversible loss of an abdominal organ, such as bowel or ovary, or develop into acute deterioration of the patient's condition up to the state of shock. Therefore, a complete history and thorough physical examination are needed to timely diagnose acute abdomen and initiate specific therapy.
Topics: Male; Female; Adolescent; Humans; Abdomen, Acute; Abdominal Pain; Abdomen; COVID-19
PubMed: 37294351
DOI: 10.1007/s00063-023-01030-x -
Tropical Animal Health and Production Oct 2023Gallibacterium anatis (G. anatis), a member of the Pasteurellaceae family, normally inhabits the upper respiratory and lower genital tracts of poultry. However, under... (Review)
Review
Gallibacterium anatis (G. anatis), a member of the Pasteurellaceae family, normally inhabits the upper respiratory and lower genital tracts of poultry. However, under certain circumstances of immunosuppression, co-infection (especially with Escherichia coli or Mycoplasma), or various stressors, G. anatis caused respiratory, reproductive, and systemic diseases. Infection with G. anatis has emerged in different countries worldwide. The bacterium affects mainly chickens; however, other species of domestic and wild birds may get infected. Horizontal, vertical, and venereal routes of G. anatis infection have been reported. The pathogenicity of G. anatis is principally related to the presence of some essential virulence factors such as Gallibacterium toxin A, fimbriae, haemagglutinin, outer membrane vesicles, capsule, biofilms, and protease. The clinical picture of G. anatis infection is mainly represented as tracheitis, oophoritis, salpingitis, and peritonitis, while other lesions may be noted in cases of concomitant infection. Control of such infection depends mainly on applying biosecurity measures and vaccination. The antimicrobial sensitivity test is necessary for the correct treatment of G. anatis. However, the development of multiple drug resistance is common. This review article sheds light on G. anatis regarding history, susceptibility, dissemination, virulence factors, pathogenesis, clinical picture, diagnosis, and control measures.
Topics: Female; Animals; Poultry; Chickens; Pasteurellaceae Infections; Pasteurellaceae; Virulence Factors; Escherichia coli; Poultry Diseases
PubMed: 37889324
DOI: 10.1007/s11250-023-03796-w -
Clinical Microbiology and Infection :... Sep 2023Peritonitis is a serious complication in patients undergoing automated peritoneal dialysis (APD) that increases morbidity and frequently disqualifies patients from the...
OBJECTIVES
Peritonitis is a serious complication in patients undergoing automated peritoneal dialysis (APD) that increases morbidity and frequently disqualifies patients from the peritoneal dialysis programme. Ceftazidime/avibactam (CAZ/AVI) is a potential treatment option for APD patients with peritonitis caused by resistant Gram-negative bacteria, but limited data exist on systemic and target-site pharmacokinetics (PK) in patients undergoing APD. This study set out to investigate the PK of CAZ/AVI in plasma and peritoneal dialysate (PDS) of patients undergoing APD.
METHODS
A prospective, open-label PK study was conducted on eight patients undergoing APD. CAZ/AVI was administered as a single intravenous dose of 2 g/0.5 g over 120 minutes. APD cycles were initiated 15 hours after the study drug administration. Dense PDS and plasma sampling was performed for 24 hours after the start of administration. PK parameters were analysed with population PK modelling. Probability of target attainment (PTA) was simulated for different CAZ/AVI doses.
RESULTS
PK profiles of both drugs in plasma and PDS were similar, indicating that the two drugs are well suited for a fixed-dose combination. A two-compartment model best described the PK of both drugs. A single dose of 2 g/0.5 g CAZ/AVI led to concentrations that far exceeded the PK/PD targets of both drugs. In the Monte Carlo simulations, even the lowest dose (750/190 mg CAZ/AVI) achieved a PTA of >90% for MICs up to 8 mg/L (The European Committee on Antimicrobial Susceptibility Testing epidemiological cut-off value for Pseudomonas aeruginosa) in plasma and PDS.
DISCUSSION
On the basis of PTA simulations, a dose of 750/190 mg CAZ/AVI would be sufficient to treat plasma and peritoneal fluid infections in patients undergoing APD.
Topics: Humans; Ceftazidime; Anti-Bacterial Agents; Prospective Studies; Drug Combinations; Microbial Sensitivity Tests; Peritoneal Dialysis
PubMed: 37301439
DOI: 10.1016/j.cmi.2023.06.002