Is shorter also better in the treatment of Clostridioides difficile infection?

OBJECTIVES: To assess the effectiveness of shortened regimens of vancomycin or fidaxomicin in the treatment of Clostridioides difficile infection (CDI). METHODS: Adult patients with CDI hospitalized from January 2022 to May 2023 were included in this observational study. In patients with CDI treated with vancomycin or fidaxomicin, antibiotic treatment was discontinued after either 5 or 7 days of vancomycin or 5 days of fidaxomicin if there was a clinical response and improvement in laboratory parameters. The control cohort was treated with the standard 10 day regimen of either vancomycin or fidaxomicin. The follow-up was 60 days. Causative C. difficile strains were characterized by ribotyping and toxin gene detection when available. RESULTS: Twenty-five patients (median age 76 years) received shortened treatment with vancomycin (n = 21), or fidaxomicin (n = 4). Five cases fulfilled the criteria for severe CDI. Twenty-three patients completed follow-up; two died from causes other than CDI, and two developed recurrent CDI (8.0%). Ribotypes (RTs) 001 and 014 were the most prevalent with 20% each. In two C. difficile isolates, binary toxin genes were detected (RTs 078 and 023). In the control group of 22 patients recurrent CDI developed in 5 patients (22.7%). No statistically significant differences were found between the groups. CONCLUSIONS: Shortened treatment regimens for CDI with vancomycin and fidaxomicin were shown to be effective in our cohort of patients compared with 10 days of treatment. The recurrence rate was lower in the study group. A larger, prospective, double-blind, randomized, multicentre study is needed to support our findings.

A word on the microbiome: considerations about the history, current state, and terminology of an emerging discipline.

Since the beginning of the 21st century, a new discipline, microbiome science, has emerged as a key part of microbiology and related biomedical and ecological sciences. Microbiome science uses highly advanced molecular genetic and bioinformatic methods to study complex microbial communities. Unlike isolated microbes, microbial communities shaped by the environment, referred to as microbial consortia or microbiomes, follow their own laws that allow for significant functional specialization. The synthesis of multimethodology and multidisciplinary data enables microbiome science to move towards a holistic picture of the microbiome in an exceptionally effective way, but on the other hand, it burdens the field with terminological ambiguity of the key terms, which consequently need to be clearly codified in accordance with the international trends in the use of technical nomenclature. To this end, we present in our article the official position of the Czech Microbiome Society of the J. E. Purkyne Czech Medical Society on the use of appropriate Czech terms in both professional and general communication.

Pathogenesis of infections caused by SARS-CoV-2.

SARS-CoV-2 primarily causes mucosal infections of the respiratory or intestinal tract. This virus, unlike other viruses responsible for similar mucosal infections, is characterized by an extraordinary ability to modify the immune response at several levels and thus cause a range of clinical complications. These manipulations create a false picture of pyogenic bacterial infection. The course of the disease is mainly determined by the natural mucosal immunity which can stop the virus from multiplying in the early stages of infection before it can exert its influence. COVID-19 has two main clinical forms: mucosal infection (respiratory or intestinal) and pneumonia. Pneumonia is associated with activation of the vascular endothelium and a procoagulant state. Viremia does not belong to the standard course of the disease. Affecting organs other than the lungs - whether during an active infection or later (long covid) - is usually caused by immunopathological reactions or hormonal regulation disorders.

Hyperbaric oxygen enhances collagen III formation in wound of ZDF rat.

Diabetic foot ulcer (DFU) is a serious complication of diabetes and hyperbaric oxygen therapy (HBOT) is also considered in comprehensive treatment. The evidence supporting the use of HBOT in DFU treatment is controversial. The aim of this work was to introduce a DFU model in ZDF rat by creating a wound on the back of an animal and to investigate the effect of HBOT on the defect by macroscopic evaluation, quantitative histological evaluation of collagen (types I and III), evaluation of angiogenesis and determination of interleukin 6 (IL6) levels in the plasma. The study included 10 rats in the control group (CONT) and 10 in the HBOT group, who underwent HBOT in standard clinical regimen. Histological evaluation was performed on the 18th day after induction of defect. The results show that HBOT did not affect the macroscopic size of the defect nor IL6 plasma levels. A volume fraction of type I collagen was slightly increased by HBOT without reaching statistical significance (1.35+/-0.49 and 1.94+/-0.67 %, CONT and HBOT, respectively). In contrast, the collagen type III volume fraction was ~120 % higher in HBOT wounds (1.41+/-0.81 %) than in CONT ones (0.63+/-0.37 %; p=0.046). In addition, the ratio of the volume fraction of both collagens in the wound ((I+III)w) to the volume fraction of both collagens in the adjacent healthy skin ((I+III)h) was ~65 % higher in rats subjected to HBOT (8.9+/-3.07 vs. 5.38+/-1.86 %, HBOT and CONT, respectively; p=0.028). Vessels density (number per 1 mm2) was found to be higher in CONT vs. HBOT (206.5+/-41.8 and 124+/-28.2, respectively, p<0.001). Our study suggests that HBOT promotes collagen III formation and decreases the number of newly formed vessels at the early phases of healing.

Repeatedly negative PCR results in patients with COVID-19 symptoms: Do they have SARS-CoV-2 infection or not?

OBJECTIVE: To point out possible infection with SARS-CoV-2 in symptomatic patients despite repeated negative nasopharyngeal swab tests for SARS-CoV-2. MATERIAL AND METHODS: A retrospective observational study carried out at the Na Bulovce Hospital from the beginning of the pandemic until November 2020 included patients (1) who had symptoms compatible with COVID-19; (2) whose nasopharyngeal swab PCR tests in the presence of acute respiratory infection symptoms yielded two consecutive negative results; (3) in whom SARS-CoV-2 infection was subsequently confirmed by serology. Basic demographic and epidemiological data, symptoms, laboratory test results, X-ray findings and timing of virological tests were analysed for these patients. RESULTS: Seventeen patients met the inclusion criteria, 14 men and three women, aged 19-84 years with a median of 59 years, of whom 14 were hospitalized and three were treated as outpatients. Only seven patients were aware of the previous contact with an infected person. The main symptoms were fever, cough, headache, weakness, fatigue and shortness of breath. Pneumonia was found in 12 patients, four of whom developed respiratory insufficiency requiring ventilatory support. Most patients showed a uniform combination of haematological, biochemical and radio-logical findings: absence of eosinophils and increased polymorphonuclear/lymphocyte ratio; elevation of serum lactate dehydrogenase; elevation of CRP without rise of procalcitonin; typical chest CT or X-ray findings. All patients recovered. Coronavirus antigen test was performed in six patients, with all of them testing negative. SARS-CoV-2 infection was confirmed serologically by the detection of specific IgG and IgA in all 17 patients and also IgM in six patients, not before day 8 of the onset of symptoms. CONCLUSIONS: Our study showed that some patients with acute COVID-19 may test repeatedly negative by nasopharyngeal swab PCR. These cases should be interpreted as a low viral load in the upper respiratory tract rather than false negativity of PCR. Such alternative is not envisaged in the algorithms used. Considering our results, the following recommendation can be made: If, despite negative PCR tests, COVID-19 is still suspected based on clinical symptoms and epidemiological evidence, preliminary diagnosis can be made on the basis of comprehensive assessment of the laboratory test and X-ray findings. Final confirmation of the aetiology relies on serological tests performed two weeks after the onset of symptoms.

Hyperbaric oxygen influences chronic wound healing - a cellular level review.

Chronic wound is a serious medical issue due to its high prevalence and complications; hyperbaric oxygen therapy (HBOT) is also considered in comprehensive treatment. Clinical trials, including large meta-analyses bring inconsistent results about HBOT efficacy. This review is summarizing the possible effect of HBOT on the healing of chronic wound models at the cellular level. HBOT undoubtedly escalates the production of reactive oxygen and nitrogen radicals (ROS and RNS), which underlie both the therapeutic and toxic effects of HBOT on certain tissues. HBOT paradoxically elevates the concentration of Hypoxia inducible factor (HIF) 1 by diverting the HIF-1 degradation to pathways that are independent of the oxygen concentration. Elevated HIF-1 stimulates the production of different growth factors, boosting the healing process. HBOT supports synthesis of Heat shock proteins (HSP), which are serving as chaperones of HIF-1. HBOT has antimicrobial effect, increases the effectiveness of some antibiotics, stimulates fibroblasts growth, collagen synthesis and suppresses the activity of proteolytic enzymes like matrix metalloproteinases. All effects of HBOT were investigated on cell cultures and animal models, the limitation of their translation is discussed at the end of this review.

Air flight barotrauma and meningitis: causality seems real.

BACKGROUND: Barotrauma to the middle-ear cavity and paranasal sinuses is a relatively common flight-related health problem. Occasionally, it may result in severe mechanical or infectious intracranial complications; these have been rarely reported to date. OBJECTIVE: Four cases of acute bacterial meningitis following air travel are presented, and its pathogenesis is briefly described. CONCLUSION: Neurological symptoms occurring after air flight should prompt proper investigation. Otitis media and sinusitis are common primary focuses of bacterial meningitis. Severe complications of air flight barotrauma may be underreported.

Serious imported infections: A focus on Chromobacterium violaceum.

The authors report on the main threats in the Czech Republic connected with travel and migration. The spectrum of diseases differs in the group of Czech citizens departing abroad, especially in the tropics and subtropics, from infections detected in foreigners, in particular from developing countries.A case report of sepsis caused by the exotic bacteria Chromobacterium violaceum is added to illustrate the potential severity of imported infection. A 54-year-old man acquired the infection during a diving holiday in Thailand. The disease began as a local ear infection, and progressed to septic shock with multiple organ failure and ischemic necrosis of all extremities. The original infection was cured but the patient eventually died due to subsequent complications. In order to properly diagnose and treat such rare diseases, we feel useful to study their pathogenesis (Tab. 2, Ref. 16). Keywords: imported infections, Chromobacterium violaceum, sepsis.

Laboratory options for risk assessment of pregnancy pathologies.

The most effective method of screening for chromosomal abnormalities and evaluating the risk of pregnancy pathologies in the first trimester is combined screening. The algorithm of screening is based on the combination of maternal age, measuring of the nuchal translucency and the fetal heart rate and analysis of the placental products of free ß-hCG and PAPP-A. For the screening of preeclampsia, placental growth factor (PlGF) is added. To distinguish between preeclampsia and other pathologies caused by placental dysfunction it is recommended to also extend the screening with selected immunological markers. We concluded that elevated biochemical and immunological markers can help to predict the threat of preeclampsia in the third trimester. Some markers can probably predict the development of particularly severe pathological conditions.

Effect of shock waves combined with cytostatics on the growths of tumors in vivo.

Based on their field of application, the physical parameters of shock waves differ. Experiments referred to in this article used tandem shock waves generated on the surface of a composite anode. There, individual pores of the anode produce multichannel discharges. The composite anode may have a variety of shapes, which, consequently, influence the arrangement of the entire apparatus and the area of their application. Experiments referred to in this article utilise an anode divided into two parts that generated tandem shock waves. The previously conducted experiments have clearly shown that the effect of a tandem shock wave can be very well localized in the focal area, causing necrosis and apoptosis of the tumor cells, and enhancing the effect of cytostatics. This study investigated the effect of tandem shock waves with concomitantly administered cytostatics. We conducted our experiments on Lewis rats. The rats were injected with syngeneic sarcoma tumor cells intradermally and caudally on both the right and left sides. The highest rate of tumor growth inhibition was observed in the cisplatin-treated group that was subsequently treated with shock waves. The effect of shock waves on cell membranes is well described as they increase their permeability due to sonodynamic effect induced by cavitation. The results of experiments referred to in this article conducted in vivo in experimental animals enable us to note that the shock wave increases the effect of chemotherapy administered.

PVA and PCL nanofibers are suitable for tissue covering and regeneration.

The aim of the study was to evaluate the safety and efficacy of a new therapeutic approach to skin defects resulting from split thickness grafting. Within the study, nanofiber-based dressings fabricated using polyvinyl alcohol (PVA) and poly-ε-caprolactone (PCL) were used, with different mass density. The study was performed in 1 female minipig. Nine defects (approx. 4x4 cm) were made in the superficial skin layer. The tested materials were applied to the squared skin defect and covered by a Jelonet paraffin gauze, sutured in the corners of the defects. The animal was monitored daily during the healing process (21 days). On day 5, 12, and 27, the healing of the wound was evaluated, and a biopsy was performed for further histologic testing. At the end of the study (on day 27 after the procedure), the animal was euthanized, and a standard pathologic evaluation was performed. We can conclude that the nanofiber scaffold which was well tolerated, could be used as a smart skin cover which could be functionalized with another bioactive substances directly on the surgeon table, among potential bioactive substances belong platelet derivatives, antibiotics, etc.

[Experimental promotion of liver regeneration after portal vein branch ligation]. / Moznosti experimentálního ovlivnení regenerace jaterního parenchymu v souvislosti s ligací vetví portální zíly.

INTRODUCTION: Portal vein embolization or ligation (PVE/PVL) is part of most multi-stage liver procedures in the case of low future liver remnant volume (FLRV). PVE initiates compensatory hypertrophy of non-occluded liver parenchyma. This hypertrophy is stimulated by an increased volume of portal blood in the non-occluded veins. PVE results in adequate FLRV growth necessary for resection only in 63-96% patients. The aim of this publication is to summarize the possibilities of influencing liver regeneration after PVE/PVL in an experiment using cytokines (TNF-α, IL-6), a monoclonal antibody against TGF-ß1 (MAB TGF-ß1) and mesenchymal stem cells (MSC). METHODS: The experimental model of PVE/PVL was chosen as best compatible for potential use in human medicine. 9 (control group), 9 (TNF-α group), 8 (IL-6 group), 6 (MSC group) and 7 piglets (MAB TGF-ß1 group) were enrolled in individual studies. We performed laparotomy with PVL of the right-sided liver lobes under general anaesthesia. The following amounts of substances were applied in the non-occluded portal vein branches immediately after PVL: physiological solution (control group), recombinant porcine TNF-α (5 µg/kg), recombinant porcine IL-6 (0.5 µg/kg) and MSC (8.75, 14.0, 17.0, 17.5, 43.0 and 61.0 x 106 MSC). MAB TGF-ß1 was applied 24 hours after PVL (40 µg/kg). Biochemical parameters were analysed repeatedly and FLRV ultrasound assessments were performed in the postoperative period. The experiments were ended on postoperative day 14 by sacryfiing the animals under general anaesthesia. Liver samples of hypertrophic and atrophic liver parenchyma were analysed. RESULTS: Repeated ultrasound assessments of the effects of MSC, TNF-α, IL-6 and MAB TGF-ß1 compared with the physiological solution in the control group demonstrated statistically significant acceleration of FLRV growth in the experimental groups. For MSC, maximum growth was observed between postoperative days 3 and 7, on day 7 for TNF-α, between days 3 and 7 for MAB TGF-ß1 and on day 7 for IL-6. Serum levels of AST and ALT increased after PVL and MSC whereas other biochemical parameters showed no statistically significant differences. We identified individual MSC using immunohistochemistry in the hypertrophic tissue of the MSC group. A statistically significant difference was observed in the number of binucleated hepatocytes, with their increased concentration in the IL-6 group. CONCLUSION: Application of IL-6, TNF-α, MAB TGF-ß1 and MSC seems to provide suitable stimulation for achieving faster FLRV growth. Nevertheless, many controversial questions still remain to be answered with respect to the mechanism of their respective effects.Key words: liver regeneration portal vein embolization large animal experiment mesenchymal stem cells cytokines.

Pelvic actinomycosis and IUD.

OBJECTIVE: To summarize knowledge about the mana-gement in women with proven actinomyces in uterine cervix and inserted intrauterine device (IUD). DESIGN: An overall review. RESULTS: Actinomycosis is an uncommon but important subacute or chronic infection caused by anaerobic or microaerophilic bacteria, mainly within the Actinomyces genus. Actinomycosis can affect various organs and tissues in the human body, often manifesting draining sinuses, abscess formation and fibrosis. The pelvic form in women is the most common in the developed countries. Long-duration treatment with antibiotics can be completely effective even in cases of heavy disease. Although pelvic actinomycosis is predominantly associated with the longstanding use of intrauterine device, the risk of future symptomatic infection is extremly low even in women with a cervical Pap smear positive for actinomyces-like organisms (ALO). Therefore the identification of actinomycetes by cytology after cervical Pap smears is not diagnostic nor predictive of any disease because the actinomycetes normally reside in the female genital tract. In the absence of symptoms, patients with ALO on a Pap test do not need antimicrobial treatment or IUD removal. Nevertheless, women choosing an IUD for contraception should know that there is very low risk of developing the infection in later years after insertion. CONCLUSION: The sources of literature conclude that removal of the intrauterine device in a patients with a positive ALO in the uterine cervix is not necessary and antibiotics treatment is not required. However, IUD must be changed at least every five years in order to limit the risk of the development of pelvic actinomycosis.

Absence of BRAF mutation in pheochromocytoma and paraganglioma.

Pheochromocytomas and Paragangliomas (PHEO/PARA) are rare endocrine tumors originating from the adrenal medulla. More than 20 genes are involved in the tumorigenesis of these tumors, but a substantial part of the causative genetic events remains unexplained. A recent study has reported the presence of the activating BRAF V600E mutation in PCC, suggesting a role for BRAF activation in tumor development. Other studies have not find this mutation. This study investigates the occurrence of the BRAF V600E mutation in these tumors.A cohort of 64 PHEO/PARA were screened for the BRAF V600E mutation using direct Sanger sequencing and QRT-PCR.All cases investigated displayed wild-type without V600E BRAF mutationTaken together with all previously screened tumors up to date, only 1 V600E BRAF mutation has been found among 427 PCCs. These findings imply that the V600E BRAF mutation is a rare event in PHEO/PARA.

[Antibiotic treatment of clostridial colitis]. / Antibiotická lécba klostridiové kolitidy.

The advantages and disadvantages of various antibiotics used in the treatment of Clostridium difficile infection (CDI) are compared with respect to their pharmacokinetic and pharmacodynamic properties. Recommendations are made for their optimal use in clinical practice. Metronidazole is suitable for the treatment of mild forms of CDI which are essentially self-limiting. Vancomycin kills clostridia reliably but the treatment is encumbered with considerable risk of recurrence. This can be decreased by shortening the treatment to seven days and then switching to a (pulse, taper, chaser) regimen to prevent recurrence or by active restoration of the intestinal ecosystem (fecal transplant). Fidaxomicin works faster than vancomycin and is associated with a lower risk of recurrence. Thus, it can be profitably used in patients with impending ileus and also in those whose medical condition does not allow prolonged treatment. The duration of fidaxomicin treatment could be reduced to as few as five days. Rifaximin does not have a clear place in the treatment of CDI because no compelling data are available on its efficacy in this disease. The risk of resistance is also important. Tigecycline is a promising antibiotic for parenteral use. According to the available data, it should be more effective than intravenous metronidazole which has been considered the drug of choice.Clostridial colitis is associated with intestinal dysmicrobia which is the major cause of recurrence. Severe dysmicrobia cannot be treated by antibiotics but only by gut flora restoration; stool transplant from a healthy donor is the only proven therapy for this condition.

[Pyoderma Gangrenosum Mimicking Necrotising Fasciitis after Rotator Cuff Reconstruction]. / Gangrenózní pyodermie po rekonstrukci rotátorové manzety ramena pripomínající nekrotizující fasciitidu.

UNLABELLED: Gangrenous pyoderma is a rare complication of surgical treatment mimicking bacterial necrotizing fasciitis. The characteristic symptoms include a pre-existing immune disorder, negative results of the relevant microbiological examinations, no response to any antibiotic therapy, and deteriorating of the condition after radical debridement. Another typical feature is a discrepancy between an ominous appearance of the wound accompanied by leucocytosis and an elevated CRP level, and the patient s good general condition with low-grade fever and no signs of sepsis. The case of a 68-year-old man who underwent an elective open reconstruction of rotator cuff tears of the left shoulder is presented. The surgery was complicated with pyoderma gangrenosum that was first treated unsuccessfully by repeated revision surgery and broad-spectrum antibiotic therapy. The patient was ultimately cured with corticosteroids. The sequellae included limited motion of the shoulder joint and extensive destruction and scarring of the adjacent soft tissue. KEY WORDS: gangrenous pyoderma, necrotizing fasciitis, corticosteroids.

Necrotizing pneumonia due to clonally diverse Staphylococcus aureus strains producing Panton-Valentine leukocidin: the Czech experience.

A prospective study (2007-2013) was undertaken to investigate clinical features and prognostic factors of necrotizing pneumonia caused by Staphylococcus aureus producing Panton-Valentine leukocidin (PVL) in the Czech Republic. Twelve cases of necrotizing pneumonia were detected in 12 patients (median age 25 years) without severe underlying disease. Eight cases occurred in December and January and the accumulation of cases in the winter months preceding the influenza season was statistically significant (P < 0·001). The course of pneumonia was very rapid, leading to early sepsis and/or septic shock in all but one patient. Seven patients died and mortality was fourfold higher in those patients presenting with primary pneumonia than with pneumonia complicating other staphylococcal/pyogenic infection elsewhere in the body. The S. aureus isolates displayed considerable genetic variability and were assigned to five lineages CC8 (n = 3), CC15 (n = 2), CC30 (n = 2), CC80 (n = 1), and CC121 (n = 3) and one was a singleton of ST154 (n = 1), all were reported to be associated with community-acquired infection. Four strains were methicillin resistant. The high case-fatality rate can only be reduced by improving the speed of diagnosis and a rapid test to detect S. aureus in the airways is needed.

[Treating diphtheria in the 21st century]. / Lécba záskrtu v 21. století

The existing recommendations for treatment of diphtheria involve the use of a hyperimmune serum neutralizing diphtheria toxin and subsequent penicillin therapy killing the pathogen. Unfortunately, diphtheria antitoxin is no longer available in the Czech Republic and this condition seems to remain permanent. Thus, the whole strategy for diphtheria treatment must be changed. Instead of penicillin, antibiotics inhibiting bacterial protein synthesis such as clindamycin or linezolid should be administered. Macrolides could be appropriate in mild to moderate disease.