Factors Predisposing to Clostridium Difficile Infection - Essay Example

Clostridium difficile Factors predisposing to C. difficile infection: Diarrhea is commonly associated with the use of antibiotics that are capable ofkilling/ arresting growth of infection causing organism but in some cases this association could be related with the proliferation and colonization of opportunistic pathogen Clostridium difficile. In other words C. difficile- associated diarrhea (CDAD), a life threatening or fatal disease occurs when an individual is on the course of antibiotics (Bignardi, 1998). Colonization of C. difficile is therefore linked from asymptomatic carrier state to fulminant pseudomembranous colitis (Kyne, 2001, a). C. difficile is a spore forming, anaerobic bacilli, shows positive Gram reaction and is known to be associated with nosocomial diarrhea. It is an etiological representative of pseudo membranous colitis (PMC) and 15-25% of diarrhea associated with the intake of antibiotics (Bartlett, 2002). It is known that bacteria adapt to the shifting environment and so do their response to antibiotics, making them resistant and more virulent. Severity of CDAD is also associated with similar paradigm. In severe and acute cases CDAD may cause ulceration and hemorrhage. The disease encompasses diarrhea, fever, amplified fecal leukocytes, abdominal cramping and dehydration; leading to hypoalbuminaemia, toxic megacolon, colonic perforation and PMC causing amplification in morbidity and mortality (Poutanen, 2004). Pathogenic Clostridium difficile produces exotoxins- A and B. They have potential role in causing CDAD (Pothoulakis, 1996). Strains producing toxin either A+ B+ or A‑B+ are responsible for virulence while non-toxin producing strains are non virulent and do not cause diarrhea. In normal individuals, enteric pathogens are prohibited from establishment due to native intestinal microflora, contributing to host’s defense mechanism. Clostridium difficile is a potent pathogen that successfully establishes infection because of its immense ability to produce toxins thereby paving the way for C. difficile colonization. Toxins generated by C. difficile are highly enterotoxic and cytotoxic. Healthy individuals possess antibodies serum IgG and intestinal secretory IgA against toxin A, and efficiently bind to the intestinal receptors of toxin A. This is a condition where humoural response to toxin A is hampered and thus C. difficile finds way for proliferation. The action of toxin A causes disruption of epithelial cells, enhanced fluid emission, damage of mucosa, irritation and tenderness due to enhanced permeability of tight junctions causing diarrhea or PMC (Kyne, 2001, b). Diarrhea in turn leads to loss of water and minerals/ electrolytes leading to a complicated colon perforation, megacolon or peritonitis. Clostridium difficile is associated with diarrhea, and is of medical progress. Antimicrobial therapy is the major predisposing factor. It is observed that immunosuppression and conditions that disturb the normal intestinal flora have been implicated. Various studies have been conducted that related IgG antibody with toxin A as a protective mechanism (Kyne, 2000). In some other studies it is emphasized that when toxin A is secreted IgG respond to the same as a measure to protect the CDAD reoccurrence (Kyne, 2001, b). On evaluating the C. difficile antigens, toxin A and toxin B, antibody responses, patients reporting recurrent episodes of CDAD show significant low level of IgM antibodies against non-toxic antigens, indicating that immune response is not only for toxin A and toxin B but also play an imperative part in the proliferation of disease (Kyne, 2001, b). Most of the bacterial species possess SLPs i.e. S-layer (surface layer) paracrystalline surface protein array (Calabi, 2001; Karjalainen, 2001). It is reported that two surface proteins are found to be associated with C. difficile, they are derived from single gene sequence, the higher molecular weight protein (MW 42-48) and lower mol. wt. protein (MW 32-38) (Calabi, 2002; Karjalainen, 2002). The lower molecular weight proteins possess antigenic epitopes (Cerquetti, 1992, Taekeoka, 1991, Pantosti, 1988). On the other hand higher mol. wt. protein is found to be associated with the adhesion, which is responsible for the bonding of the bacterium to the intestinal mucosa (Calabi, 2002). It was reported by Drudy et al (2004) that IgM antibody against the SLPs of C. difficile is connected with a reduced risk of recurrent CDAD. This is imperative for the bacterial colonization, maintenance of infection and also for the host immune reaction. Prevalence of CDAD is universal, it is usually induced in hospitals and involves hospital staff or care takers, and moreover it can make the relatives of patient as carrier. It is known to affect 15-30% of the population taking the course of antibiotics (Gogate, 2005). It is reported that CDAD associated mortality is ~ 17%, it is more in elderly group due to numerous co-morbidities (Chandler, 2007). It is also reported that Clostridium difficile finds association with non-hospital situations too as it is capable of infecting domestic and wild animals, contaminated meat can be the source of human infection such incidence is said to be community-acquired C. difficile. Various risk factors are associated with C. difficile infection: A. Drugs 1. Antibiotics: broad spectrum antibiotics disrupts normal intestinal microflora. Amongst these, clindamycin (Cleocin) is known to cause C. difficile colitis, others are- amoxicillin, ampicillin, cephalosporin. Occasionally, penicillin, erythromycin, trimethoprim, and quinolones including ciprofloxacin are also known to cause C. difficile colitis. Tetracycline, metronidazole, vancomycin and gentamicin are known to cause colitis under rare conditions. Use of antibiotic, followed by C. difficile colonization induce diarrhea in individual. It is observed that 30% of reported positive samples were from those who have undergone the course of antibiotics during their hospital stay as compared to 7% samples from those who have not taken antibiotics (Vaishnavi, 1999). 2. Immunosuppressive agents: these agents are related to CDAD proliferation, as these agents directly affect the immune system paving the way for symptomatic CDAD (Bartlett, 2002). It is also observed that serum level of Immunoglobulin G antagonizing toxin A is elevated particularly in patients with mild CDAD. In some cases besides having good immune response, the patient display prolonged and recurrent C. difficile- associated diarrhea. Immunosuppressive drugs especially corticosteroids are unable to mount an effective IgG response (Kyne, 2001). Patients undergoing organ transplants display C. difficile diarrhea (Keven, 2004, West, 1999). Patients with cystic fibrosis also display CDAD. 3. Proton pump inhibitors (PPI): Gastric acid suppressive drugs increase the pH of stomach as a result the individual is prone to enteric infections especially to the spore-bearing organisms. PPI alters the microflora of intestine by interfering with parietal cell enzyme H+/K+-ATPase. Changes in the microflora enables C. difficile proliferation (Bashford, 1998). PPI also affect immune function and the production of toxin and therefore there is a direct co-relation between the gastric acid suppressive drugs and community acquired CDAD. It is observed that most of the physicians do have a habit of prescribing acid suppressive drugs thereby enhancing the chances of CDAD infection. Hospitalized individuals who are on antibiotic therapy along with PPI are more susceptible to CDAD. Restricting the frequent use of PPI will definitely diminish the chances of CDAD. 4. Cancer Therapeutics: Cancer chemotherapeutics also disturbs the normal host intestinal microflora, thereby allowing C. difficile to proliferate (Emoto, 1996). A. Non-Drug Risk Factors: 1. Host risk factors: Age of the individual, two groups who are at potential risk of disease are infants and elderly. 2. Underlying diseases like inflammatory bowel disease, bowel ischaemia, mechanical bowel cleaning, other enteric infections which are responsible for changing microflora, prolonged presence of nasogastric tube for enteral feeding, use of electronic rectal thermometers, use of enemas, gastrointestinal stimulants and stool softners 3. Impaired immunity: immuno-compromised individuals are prone to CDAD infection. Decrease in immunity could be due to irradiation, radiation therapy, malnourishment, any kind of shock, if the individual is taking chemotherapy. 4. Factors related to C. difficile: number of cells, adhesion property of the strain to intestinal mucosa, strain’s ability to produce toxins, occurrence of any other microflora that affects the toxin production. 5. Factors related to environment: it is observed that most of the hospital wards, nursing homes, child care centres, ICU are the habitat of C. difficile. Moreover the toilet and facilities like bathtubs in the toilets make the patient catch the infection. Physicians stethoscope, thermometers also enhance the chances of cross infection. 6. It is therefore Clostridium difficile associated diarrhea is emerging as a major health concern as it marks the presence of a plethora of risk factors apart from antibiotics. It is imperative to recognize the patients possessing high risk of CDAD for their quicker administration for diagnosis. 7. Length of hospital stay: provides more exposure to contaminated environmental surface, shared instrumentation, hospital personnel hands and also infected partner sharing room (Barbut, 2001). Once the infection outbreaks, it spreads to the entire hospital environment. The most important is that the individual staying in the hospital is exposed to the spores in the hospital environment which find their germination at any time when they find suitable conditions and when the host defense mechanism is hampered, or when the host is immune-compromised or when the host is on the course of antibiotics. CDAD is now an established cause of iatrogenic, nosocomial disease with considerable morbidity and mortality and is endemic in hospitals all over the world. The range of the disease is also extensive, from asymptomatic to PMC, becoming a saddle on the health services, in terms of economic burden and also prolonged hospitalization and in rare cases of isolation, leading to ward closure (Khan, 2003). It is therefore imperative that these factors must be kept in consideration for the quick diagnosis of CDAD. This is essential for the prompt treatment of CDAD and to prevent cross-infection in the hospitalized patients. It is crucial for the care takers and nursing staff to practice best infection control measures especially after defecations. The concern demands action by hospital management to take utmost precautions for the health, cleanliness and hygiene of the patients. To overcome the trepidation caused by C. difficile policies have been laid down to control CDAD infection. The current policies are mostly laid with an intention to give information to the working staff along with the knowledge to reduce cross-infection. They encompass: 1. Awareness: in the present scenario awareness about the public health risk by C. difficile is confined to physicians and to some extent to the nursing staff. It is imperative that this should be passed on to the patient with details explaining why it is vital to understand the potentials and capabilities of C. difficile. The participation of patient in preventing the disease is not emphasized in the current policies but it is imperative that the patient must participate whole heartedly to prevent the spread of disease from him/her to others. 2. Environment cleaning: it is a tough challenge as the current policies stress upon the cleanliness of the hospital. The policies emphasize upon the fact that the spores of C. difficile liberated by the patient are not killed by the routine environment cleansing agents, detergents and even by alcohol-based gels. It is therefore essential to clean the contaminated surfaces with 10% sodium hypochlorite, hands with soap or with chlorhexidine as they are capable of eliminating C. difficile spores from hands (Gerding, 2008). It is imperative that patient must be explained to wash the hands thoroughly after using toilet and should not touch anything before cleaning hands. Proper toilet disposal must be performed else spores adhere to the commode can contact the skin and thus finds way for their entry into the body. It is essential that patient should also be explained about the acquisition of infection by C. difficile in terms of direct patient to patient contact, contact of the patient with health care staff and indirect spread via environmental contamination. 3. An accurate and rapid diagnosis: it is essential that regular diagnostic stool examinations be performed for the presence of toxin A and toxin B, this is performed routinely as a part of National Health Associated Infection Surveillance program (Infection control services). 4. Surveillance for Clostridium difficile: community acquired infection is established within 72 hours of hospitalization, whereas hospital acquired infection is established after 72 hours of hospitalization. These cases could be due to endogenous, i.e. the infection arose die to patients own flora or it may occur from exogenous infection. The best way to manage infection is through appropriate antibiotic use (Infection control services). 5. Appropriate treatment and patient management: based on epidemiological investigations, patients can be categorized as- (i) Sporadic i.e. hospital or community acquired infection. Instantaneous isolation should be done (ii) Localized cluster of cases- if repeated infection is reported in particular ward or if the cross-infection is reported. (iii) outbreak- if the infection is reported from a particular site for more than two weeks, in defined areas. In all these cases repeated fecal examinations must be performed. Antibiotics must be stopped and if given then it should be in consultation with the microbiologist to prevent the reoccurrence. It should follow the guidelines of the antibiotic prescribing guidelines. If more than one case of CDAD is reported in a ward, cephalosporin use with other patients must be avoided (Infection control services). (Infection control services). 6. Implementation of enteric precautions for symptomatic patients: As long as patient is asymptomatic, no special measures are necessary, but if the patient is symptomatic, an immediate action from the nursing staff is demanded. The current policies lay stringent emphasis on hand washing procedures using soap and water (as mentioned alcohol is ineffective). Thorough and careful hand washing is desired form the caretakers after contacting the patient or their direct settings including patient care, bedpan handling, cleaning and managing commodes or other soiled equipment. 7. Personal protective equipment: gloves and aprons, reinforcing thorough hand washing after removing protective equipments. 8. Patient Isolation: isolation of the patient must be done if the patient has diarrhea, and are CDT positive. The isolation room must possess an en-suite toilet and adequate washing facilities, or the toilet should be equipped with a commode solely for the use of patient. The door should always be kept closed. The movement of the patient is restricted and he/ she is not allowed to make any move. In case where movement cannot be avoided like (x- ray, theatres) the staff must be informed well in advance about the patient C. difficile position. Disposable gloves and aprons must be used when making contact with the patient. After 48 hours the patient can be taken away from isolation. Disposal of urine and feces must be done immediately. Decontamination of the equipments must be done e.g. blood pressure monitor, temperature probe. Visitors assisting patient must take these precautions as well, they should wash hands after touching or contacting patient and if possible then gloves must be used (Infection control services). 9. Restrictive antibiotic policy: this is highly essential of all the features as C difficile alone is accountable for 15-25% of antibiotic-associated diarrhea (AAD) and for all reported cases of pseudomembranous colitis (PMC) (Barbut, 2001). Toxin-generating C. difficile has emerged as a leading cause of nosocomial infectious diarrhea and therefore requires systematic investigation in patients with nosocomial diarrhea. Use of broad spectrum antibiotics predominantly second and third generation cephalosporins is a major risk factor influencing CDAD (Impallomeni, 1995; Spencer, 1998). Exposure to antibiotics has emerged as a majorfactor in CDAD, an effective antibiotic policy or a restrictive antibiotic policy must be implemented to prevent bacterial colonization in the gastrointestinal tract (McNulty, 1997). According to restrictive antibiotic policy, patients assumed to be infected were prescribed benzylpenicillin (iv), 1.2-1.8 g every 6 hr to eliminate the chances of streptococcal infections, trimethoprim (iv), 200 mg twice a day to control urinary tract infections and H. influenza. In case of septic shock and to eliminate gram negative bacilli, gentamicin was given (120-180 mg). For C. difficile toxin positive diarrhea, cefuroxime and total antibiotic was given, there was a remarkable decrease in the mortality rate and the incidence of C. difficile-associated diarrhea. It is therefore concluded that less use of cefuroxime should be implemented moreover, emphasis should be laid on the use of narrow-spectrum antibiotics for treating of community-acquired infections in the elderly. Any kind of outbreaks must be administered with infection control and stringent antibiotic policies (McNulty, 1997). It is observed that strict infection control policies along with amplified cleaning prevented outbreaks of C. difficile diarrhea. It must be kept in consideration that Clostridium difficile belongs to the group of bacteria responsible for causing tetanus, botulism or food poisoning and gas gangrene. This group of organism can produce spores and thus extend their survival time. It is therefore essential that proper sterilization of equipments and beddings plus hospital clothes must be performed. Instruments must be properly sterilized and autoclave must be used to carry out sterilization. This is the best way to eradicate spores of the dreaded organism. It is observed that besides possessing knowledge its implementation is not done and this can culminate as one of the reasons of ignorance and proliferation of the disease, repeated seminars and workshops must be conducted to keep the nursing staff, care takers and physicians aware about the implementation of control policies. Some of the physicians make it habit of prescribing antibiotics when not required, this must be checked to prevent the spread of disease and also for preventing the antibiotic resistant strains. Broad spectrum antibiotics must not be used if not required. Routine seminars must emphasize on the causal organism, how it spreads, susceptible population and the appropriate diagnosis. Pamphlets encompassing all the information about the organism must be given to the visitors of the patient to create awareness among the population. In some of the health care centers, isolation process of the patients is not done which is the pre-requisite. Moreover it is also observed that even the physicians do not take care to sterilize the stethoscope and instruments after the examination of infected patient and they keep on observing other patients with the same instrument. Such negligence should not be done and strict hand washing, with proper and diligent use of gloves and aprons must be done, especially when dealing with bed pan or commodes or any kind of disposal or changing of beddings or closthes is done. It is also observed that negligence is also done for environmental cleaning and this is not strictly followed but it is essential to follow and therefore awareness is very essential to prevent the nosocomial infection. References Aronsson, B., Barany, P., Nord, C. 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