Úvod

The issue of diarrhea caused by Clostridium difficile toxins (CDI) is particularly serious in elderly, polymorbid patients, in whom dehydration and disruption of the internal environment can have severe consequences. Preventive measures for clostridial enterocolitis (CE) are crucial in preventing its onset. The main focus lies in restricting antibiotic use, immediate patient isolation, a barrier system of nursing care, special operational measures on the ward, and early mobilization of bedridden patients. Increased attention must be paid to long-term care units as well as to wards where CE has occurred and where spores may survive for extended periods.

Aim of the study

The main objective of this cross-sectional study was to collect information and analyze data on the health status of patients with clostridial enterocolitis (CE) hospitalized at the Long-Term Care Unit of the hospital in Liptovský Mikuláš over a specific time period.

Sample and methodology

A cross-sectional study focused on collecting information and analyzing data at a specific point in time. The research design employed a structured observation method. The sample consisted of 116 patients with clostridial intestinal infection (CE) hospitalized at the LTCU (Long-Term Care Unit) of the Liptov Hospital – Liptovský Mikuláš over a period of 42 months (January 2021 – July 2024). The established patient selection criterion was based on the assumption that the frequency of occurrence of the defined common observation units for each patient is of fundamental substantive importance for conducting the cross-sectional study. Within the observation methodology, relevant content categories I–IV were established for quantitative expression: I. (identifying data on study respondents: age, sex, number of patients with Clostridium difficile infection for the years 2021–2024; length of hospitalization at LTCU); II. (data on respondents before admission to LTCU – transfer history, polymorbidity, antibiotic therapy); III. (data on respondents during hospitalization at LTCU – antibiotic (ATB) therapy, clinical status, onset of CDI symptoms); IV. (nursing care for patients with CDI – barrier principles of nursing care, patient nutrition and hydration, forms of ATB therapy administration, duration of hospitalization at LTCU, and discharge outcome). In accordance with Regulation (EU) 2016/679 of the European Parliament and of the Council on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and Act No. 18/2018 Coll. on the Protection of Personal Data and on Amendments to Certain Acts, a "Research Ethics Statement" became part of the cross-sectional study, with the declared written consent of the management of the Long-Term Care Unit at the hospital in Liptovský Mikuláš and the Ethics Committee of the relevant healthcare facility for the publication of workplace data.

Results and interpretation

The sample consisted of 116 patients with CE, of whom 46 were men and 70 were women. Women represented a higher proportion at 60.34% (Graph 1). The mean age of the entire sample was 79.87 years. Women had a higher mean age of 83.10 years (Graph 2). The average length of hospitalization for patients with CE at the LTCU was 24.46 weeks. Women were hospitalized longer (22.42 weeks) than men.

Approximately 90% of all forms of CDI arise following previous or concurrent antimicrobial therapy, mainly with systemically administered antibiotics. Their increase is also associated with higher patient age (over 65 years), polymorbidity, long-term hospitalization, frequent use of antisecretory drugs and proton pump inhibitors, colorectal procedures, intestinal hypomotility, and many other factors. While in 2011, 136 cases of C. difficile-related diseases were reported in the Slovak Republic, by 2017 this number had risen to 2,604 cases. However, the actual incidence of infections is higher. Many cases go undetected or are underdiagnosed, and there is a lack of standardization of reported data (State Institute for Drug Control 2016).

Graph 1 Sex

Graph 2 Mean age

Of the sample of patients with CE, 110 (94.62%) had received mono ATB therapy that was started or completed before their admission to the LTCU. The indication for ATB therapy in these patients was the presence of bronchopneumonia, enteritis, urinary tract infection, sepsis or gangrene, and febrile conditions of unknown origin (Table 1). A combination of two to four clinical entities was recorded in 67 patients (57.75%) (Graph 3).

Table 1 Clinical status before hospitalization at LTCU

Graph 3 Number of diagnoses per patient

Post-antibiotic colitis most commonly arises in connection with treatment using broad-spectrum antibiotics, but it is also often the result of nosocomial infection. Transmission occurs via the orofecal route, through contact between patients, and through contact between healthcare workers and patients. It is commonly found in the stool of 2–5% of people. Proliferation of Clostridium difficile can cause either mild diarrhea, severe diarrheal disease, or its most severe form, pseudomembranous colitis. In addition to watery diarrhea, clostridial colitis may present with the formation of pseudomembranes composed of fibrin, leukocytes, and necrotic cells (Jarčuška et al. 2014).

Polymorbidity in the sample of patients at the LTCU was complicated by immobility in 88 (75.86%) and pressure ulcers in 63 (54.31%) patients. The symptomatology of CE was dominated by diarrhea in 116 (100%) respondents. Among the other symptoms, the most pronounced were loss of appetite, general weakness, and nausea (Table 2).

Table 2 Accompanying symptoms of CE

CE infection usually manifests within 5–10 days of starting antibiotics, and in most cases it presents as a mild diarrheal illness. The onset of CE symptoms in the sample was most pronounced from the 1st to the 15th day after the start of hospitalization at the LTCU (Table 3).

Stool positivity for CDI toxin was confirmed in 107 (92.24%) patients. Diagnosis was routinely performed by detection of toxins A and B using the ELISA method; detection of specific antigen (glutamate dehydrogenase – GDH) is more accurate.

Blood cultures were also performed in 58 (50%) patients. Blood culture examination is a basic laboratory diagnostic method for bacteremia, which is typical of systemic infections, endocarditis, and other infections presenting with a clinical picture of fever of unknown origin.

Table 3 Day of onset of CE symptoms

Graph 4 Disease prevalence in CE

Bacteremia in the conditions of our hospitals most frequently relates to a diagnosis of urosepsis, as well as to infections associated with prosthetic material and catheter-related sepsis (Kukučková et al. 2011). During hospitalization, we recorded an increase in urinary tract infections of 42.14%, enteritis of 59.48%, and febrile conditions of 60.35%. Patient morbidity also included cardiovascular diseases (CVD) (Graph 4) in 109 (89.06%) and chemotherapy in 1 (1.72%). A permanent catheter (PC) was inserted in 109 (87.06%) patients throughout the entire course of hospitalization.

Clostridium difficile infection primarily affects elderly patients in hospital wards who are already weakened by another infection, particularly those with disrupted natural intestinal colonization (bacterial flora) due to treatment with broad-spectrum antibiotics (currently mainly aminopenicillins, cephalosporins, and fluoroquinolones). Risk factors include conditions following abdominal surgery where peristalsis is impaired, medications that slow peristalsis, and conditions where mucosal immunity in the digestive tract is compromised – lack of dietary protein, intestinal inflammation, etc. The risk of CDI is also increased by drugs that suppress gastric acid secretion, mainly from the PPI (proton pump inhibitor) group. Clostridial enterocolitis may recur in a patient until the normal microbial ecosystem is restored in the gut (State Institute for Drug Control 2016). Impaired intestinal motility was recorded in 37 (31.89%) patients with CE. Sepsis associated with pneumonia and meningitis is of vital importance. Bacteremia may be caused by focal infections from loci inside the body, from skin and mucosal surfaces colonized by resident microflora that penetrates through damaged mucosa or skin, from the gastrointestinal tract, or by direct introduction of contaminated material into the circulatory system. Bacteria are eliminated within minutes by the immune system. When it is overcome, signs of systemic infection appear. Mortality depends on the type of infectious agent (Krehelová et al. 2018). Combined ATB therapy is administered to patients who test positive for glutamate dehydrogenase (GDH, a specific antigen – exoenzyme produced by all C. difficile strains) and also for toxins A and B (or at least one toxin is positive). For patients with mild to moderate CDI, according to recommendations, Metronidazole should be administered at a dose of 500 mg three times daily, with a total daily dose of 1,500 mg, for a duration of 10 days. Vancomycin may also be given at a dose of 4 × 125 mg for 10 days. Vancomycin is not available in tablet form in Slovakia; however, according to the Summary of Product Characteristics (SPC), the powder can be administered orally. Increasing the dose of Vancomycin to 4 × 500 mg showed no benefit and is therefore generally not recommended. The last option is the administration of fidaxomicin at a dose of 2 × 200 mg. Fidaxomicin administration is associated with lower selection of resistance in enterococci (Jarčuška et al. 2015, p. 10).

At the time of admission of the sample patients to the LTCU, those with positive GDH received Entizol 500 mg orally in tablet form every 8 hours. For positivity of GDH and toxins A + B, combined ATB therapy was prescribed in 81 (69.82%) patients. Nurses administered a combination of Entizol 500 mg orally every 8 hours; in more severe forms, ATB therapy with Entizol was given intravenously, and according to the physician's orders, Metronidazole sol. 500 mg / 100 ml i.v. every 8 hours or Vancomycin pulv. per os 500 mg – 1000 mg every 6 hours was added. Nurses diluted Vancomycin 500 mg pulv. in 10 ml of 1/1 Physiological Saline (crystalloid isotonic solution) and administered 2.5 ml orally to patients to achieve an active substance dose of 125 mg. Nurses prepared 1 g Vancomycin pulv. in a similar manner, diluting it in 20 ml of Physiological Saline and administering 2.5 ml, i.e., a 125 mg dose orally every 6 hours. The average duration of combined ATB therapy in our patient sample was 11.34 days.

According to Kukučková et al. (2011, p. 191), metronidazole (Entizol) is the drug of first choice for enteritis. In combination with Ciprofloxacin, combined ATB therapy was administered to their patients (28) with CE, and in 11 patients this treatment induced resistance due to recurrent enteritis associated with a previous hospitalization at the LTCU. Treatment of recurrence in such patients is more complicated, lasting 14–21 days. Patients received intravenous Metronidazole alone or in combination with ATB therapy prescribed for bronchopneumonia or urinary tract infection, despite the onset of diarrhea.

Treatment of CE is relatively challenging, since most commonly used antibiotics are ineffective against diarrhea caused by Clostridium difficile toxins. First-line drugs are Vancomycin and Metronidazole. However, the success rate of this therapy has been declining in recent years. The most reliable and effective treatment method is the restoration of normal intestinal microflora, which suppresses the infection. This is achieved through so-called fecal microbiota transplantation, in which a homogenized stool sample from a healthy donor, most often a family member, is introduced into the patient's intestine. In extreme cases and life-threatening complications, surgical removal of the colon (colectomy) is necessary to save the patient's life (Krehelová et al. 2018).

Two conditions are necessary for the onset of CDI: loss of protective intestinal flora (so-called colonization resistance) and infection with toxigenic C. difficile strains. The mechanism of action of both toxins on intestinal epithelial cells differs. Toxin A (TcdA) is a typical enterotoxin that damages intestinal epithelial cells and causes fluid accumulation in the gut, resulting in watery, sometimes hemorrhagic diarrhea. Toxin B (TcdB), through its cytotoxic effect, leads to necrosis of affected cells. Numerous, characteristic island-like (map-like) ulcerations covered by pseudomembranes develop on the intestinal mucosa, clearly visible on endoscopic examination (Voth et al. 2005). The effect of toxin B on smooth muscle and the autonomic nervous system in the colon wall leads to slowing or cessation of peristalsis and the development of ileus, thereby creating an ideal environment for microorganism proliferation. Such damage may ultimately result in intestinal perforation. The terminal stage of the disease is characterized by enormous distension of the colon (megacolon) and progressive loss of the barrier function of the intestinal mucosa, followed by the penetration of intestinal bacteria into deeper tissues and then into the bloodstream. Sepsis develops, most commonly gram-negative, with rapid progression to septic shock and high mortality (Beneš, Husa, Nyč 2014). Two types of measures are necessary to prevent the transmission of an established infection – isolation of infected patients and disinfection of the environment in which they are placed. When placing a patient with suspected or confirmed CDI on the ward, epidemiological considerations are followed (Radoňák 2017), particularly the risks of spreading this infection. In the observed sample of 116 patients, only 12.93% of patients with CE were completely isolated. The main reasons for the low number of isolated patients were the structural and technical design of the LTCU, the limited capacity of rooms suitable for isolation purposes in this regard, and the higher number of patients with CE at certain times. Nurses maintained the hygienic-epidemiological regimen, and for the remaining (87%) patients, they applied the principles of barrier nursing. We observed compliance with epidemiological standards by all participating healthcare workers and other staff at the LTCU during the monitored period:

  • Healthcare personnel were educated about nosocomial infections (NI), mainly about CDI, by the ward's lead managers during internal seminars.
  • Education was also directed at assistant orderlies in healthcare and auxiliary cleaning staff.
  • Specific measures in the outbreak focus also included informing the patient and family members about the strict principles of barrier care (restricting visits to the patient in the outbreak focus).
  • Nurses ensured patient isolation for 15 patients in a single room. If this was not available, another alternative was a room with another patient also infected with CDI but without any other infectious disease.
  • Nurses clearly marked the designated room and ensured that the door to such a room was kept strictly closed.
  • Transfer and transport of patients with CDI must be considered with the provision of barrier nursing techniques. Healthcare personnel at the facility to which the infected patient is transported must be informed in advance for the implementation of strict hygienic-epidemiological regimen measures.

Among the most significant activities for preventing the occurrence and spread of NI are barrier nursing techniques (Podstatová, Pokorná 2009). The objective of barrier nursing is to prevent the spread of infection among patients and staff, protect immunocompromised patients, and prevent the spread of multiresistant strains within the healthcare facility (Zouharová 2011).

The tasks of nurses consist of applying practical barrier measures:

  • For the purpose of nursing care for a patient with CDI, nurses must allocate individualized aids exclusively for the patient's room.
  • Nurses approach the patient in accordance with barrier nursing care: (single-use protective clothing, mask, gloves, shoe covers, and alcohol-based hand disinfection). Staff must not enter the patient's room without protective health equipment.
  • A key measure that nurses must observe is specific hand hygiene to prevent the spread of infection. In CDI, one must not forget about spore formation; spores survive for a long time on surfaces (linen, tables, patient surroundings, etc.). This fact requires the use of disinfectants with a sporicidal effect and germicidal irradiation of rooms (Raková, Janošková, Dimunová 2019, p. 23).
  • After treating a patient with CDI, nurses must remove their gloves and perform mechanical hand cleansing with soap and warm water. Subsequently, after thoroughly drying hands with a disposable paper towel, they perform hygienic hand disinfection using an alcohol-based disinfectant. Alcohol-based disinfectants have excellent germicidal efficacy against gram-positive and gram-negative vegetative bacteria (including multiresistant strains). Their disadvantage is the lack of efficacy against bacterial spores or protozoan oocysts and limited efficacy against some non-enveloped viruses. The alcohol concentration should be 70–80% (Jarčuška et al. 2015; Šramová, 2013).

Nursing staff also ensured patient hydration, therapeutic nutrition, and gradual mobilization for those patients whose health condition permitted it. In the treatment of patients with CDI (100%), therapeutic nutrition was applied in a combination of form and content (liquid, bland, mushy residue-free and lactose-free [residue-free, bland RBL], mushy [MUSH], and lactose-free diet [LFD] in mutual combination, taking into account the patient's primary disease (Graph 5). A nasogastric tube was inserted in 34.11% and a permanent urinary catheter (PC) in 87.06% of patients (Graph 5).

Graph 5 Therapeutic nutrition of patients with CDI

Of the 116 patients with CDI hospitalized at the LTCU during the 42 analyzed months, 54 (46.55%) patients were successfully treated and discharged to home care. 38 (32.75%) died, and 17 (14.65%) were transferred; the reason for transfer was deterioration of health requiring surgical intervention or intensive monitoring in the ICU (Table 4).

Table 4 Discharge outcome

Conclusion

Addressing the issue of CDI in healthcare facilities requires a comprehensive approach, including adequate specific ATB therapy targeting the reduction of the highest-risk ATB groups (quinolones, broad-spectrum cephalosporins, potentiated aminopenicillins), correct indication of laboratory testing, adherence to hygienic-epidemiological measures to prevent spore spread, rigorous isolation of all infected patients with CDI, but above all, strict adherence to barrier nursing techniques by all involved healthcare professionals. Failure to observe standard epidemiological principles can lead to direct transmission of clostridial infection (CDI) from one patient to another (Novotná et al. 2020). A large proportion of infected patients remain asymptomatic and become the largest reservoir of the microbe. It is estimated that 7–11% of hospitalized patients, 5–7% of patients in social care facilities, and less than 2% of outpatients are carriers of toxin-producing C. difficile strains. The increasing incidence of diseases caused by C. difficile is driven by high antibiotic prescription rates as well as the emergence of hypervirulent strains (Krehelová, Sinajová 2018).

Author: PhDr. Jana Lauková, PhD. SZU Bratislava, Faculty of Health, based in Banská Bystrica

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