DOWNLOAD PDF ORAL IMPLICATIONS OF INFECTION IN COMPROMISED PATIENTS

Transcription

1 Chapter 1 : Infection in the immunocompromised host - Oxford Medicine Low amounts of immunoglobulins are known to play a role in many bacterial infections, e.g., upper respiratory tract infections, but have not yet been associated with specific oral conditions. T-cell defects tend to increase suspectibility towards oral infections with fungi and virus, and are also associated with periodontal disease in HIV-infected patients. Abstract Systemic diseases are of major importance in terms of prosthetic restorations supported by dental implants in healthy compromised patients. Each treatment stage from conception of the treatment plan to the long-term monitoring is under the necessity of the interdisciplinary approach to the underlying disease. Dental implant therapy in healthy compromised patients What should be kept in mind when dealing with healthy compromised patients is that there is a downward change of the reserves and general reactivity of the body. These predispose to various complications during surgery and surgery-immediate or on long term. Hence, the necessity of precautions that must be applied to such patients would arise during the surgical act, but to the same extent in the prosthetic phase or the in monitoring period [ 1, 2 ]. Systemic disorders affect the implant restoration therapy for the following reasons: Inter-relationships between body and oral cavity. By the time the patient presented to treatment by implants, the systemic disease would already have had repercussions in the oral cavity. It is known that many general maladies stand out particularly in the oral cavity, for example, patients suffering from diabetes have a periodontal disease with an aggressive evolution compared to non-diabetic patients [ 3 ]. Medications the patient receives for his systemic chronic diseases, always have a number of side effects [ 4 ]. They have consequences both to the mouth, and to the whole body: These are factors that limit and condition a number of therapeutic measures, especially in the surgical stage of dental implant therapy [ 5, 6 ]. The systemic diseases can lead to accidents and intraoperative complications. For example, a patient with heart disease can go into cardiac depression during implant surgery while endangering the vital functions. The dental implant therapy in patients with systemic disorders should be designed while taking into account long-term complications that may arise; these kind of complications are more frequent and severe than in a healthy patient. They can completely undermine the surgery. For example, in the case of a patient with osteoporosis, a bone resorption, which is characteristic for the general disease, can increase the time necessary for osseointegration; also, there is a need for a specific manner for prosthetic loading, designed to stimulate bone healing [ 7 ]. The most common types of systemic diseases we are facing are the following: Patients who smoke show changed general and local medical conditions, so, possible complications and special preventive measures will be taken into account. The treatment plan design and the accomplishment of surgical and prosthetic phases in HCP are a consequence of the full evaluation of general health and associated diseases. One of the most important aspects is antibiotic prophylaxis in the treatment of HCP with dental implants. It is mandatory in patients with myocardial infarction, those with an increased risk of bacterial endocarditis, those with diabetes, or those with an immune suppression by corticosteroids or radiation therapy [ 10 ]. In addition, the antibiotic prophylaxis is recommended in patients with anemia or liver disorders. In HCP, the whole treatment should also be related to the clinical laboratory tests, they are necessary in such cases. The most common clinical laboratory parameters investigated are the following: Stress reduction protocol is the key factor in treatment planning and surgery procedures in healthy compromised patients: Patients with cardiovascular diseases. In the case of patients with hypertension, the hypotensive medication that they receive has the side effect of xerostomia, consecutive fungal infections of the mouth candidiasis. Meanwhile, calcium blockers also used as hypotensive medication, produce gingival hyperplasia, erythema and ulcers, both in the natural dentition and around the implant. Interventions involving patients with cardiovascular diseases should be the following: Consecutive transient bacteremia is directly proportional to the amount of oral tissue trauma. In patients with heart diseases, it can cause bacterial endocarditis with very serious consequences. Therefore, surgery should be as less aggressive as possible. Antibiotic prophylaxis of bacterial endocarditis is necessary in patients with high risk: The patients who take anticoagulants demand Page 1

2 surgery procedures, which are less invasive, for example the flapless insertion of the dental implant. The bleeding is reduced to a minimum and the associated risks are reduced. The actual attitude towards these patients is to keep the anticoagulant medication because the risks of a stroke or myocardial infarction are more important than the intraoperative bleeding. Prior to surgery, in the same day, the prothrombin time test should be done [ 13 ]. Patients with endocrine disorders. Diabetes is one of the most common diseases we generally face in dental practice. The effects of this disease in the oral cavity are the following: In terms of surgical approach, the patient with diabetes should be applied an operator stress reduction protocol to prevent intraoperative hyperglycemia crisis. This protocol includes the following: It is important to know that the intervention of inserting dental implants may trigger a congestive heart failure, or on the contrary may initiate a cardio-respiratory depression in patients who suffer from thyroid disorders hyper- and hypothyroidism. Patients with chronic adrenal insufficiency Addison diabetes may be at the same risk during surgical procedures. Long-term corticosteroid therapy affects the dental implant. Blood disorders are some of the most critical diseases with echo in oral implantology. Anemia causes complications both on short term and long term: The intraoperative bleeding in such patients is high; the consequences for the patient are the possibility of postoperative edema and increased discomfort. It is associated with a high risk of secondary infections. Long-term implant survival is low due to frequent chronic infections. Leukocyte disorders induce multiple complications that can compromise the success of the implant. The most common of these is infection it can occur during any stage of treatment. Just like in patients with anemia, intraoperative bleeding is high, and the risk of postoperative edema and secondary infection are increased. Patients suffering from chronic pulmonary affections can receive an implant, but the medication for their specific pathology is with corticosteroids, producing a suppression of the body. As such, its response to surgical stress is altered. The possible complications have already been mentioned. Liver diseases interfere with surgical procedures by affecting the process of hemostasis. Intraoperative bleeding is increased in such patients, the consequences being listed above. Low capacity to metabolize medicinal substances can lead to respiratory depression. Skeletal disorders are particularly related to changes of bone resorption. Osteoporosis is present in the jawbone where the implant will be inserted, having the same features as the other bones of the body: Osteoporosis itself is not a systemic disease that contraindicates the dental implant, but it affects every stage of the treatment in a particular way: What is specific for this disease is its influence on the prosthetic phase: Another important aspect related to osteoporosis is the medication used for this disorder: Osteonecrosis of the jaw is a complication observed in patients who use oral or intravenous bisphosphonates. It is important to inform all the patients undergoing bisphosphonate therapy about the possible risks of development of osteonecrosis [ 20, 21 ]. All the patients undergoing implant placement should be questioned about the bisphosphonate therapy including the drug taken, the dosage, and length of treatment prior to surgery because all these factors influence the protocol of treatment [ 22, 23 ]. Hyperparathyroidism affects the jaws as osteoporosis does: The effects on dental implants are the same with the ones for patients with osteoporosis. Patients over 60 years old have a physiological adaptability to diminished stress, which is why they are treated similar to patients with mild medical general conditions. It requires a high level of caution intra-and post-operatively. If there are systemic disorders, they are taken into account in determining the therapeutic approach. Medications that seniors routinely take, interfere with the oral cavity status by the side effects [ 24, 25 ]. Smoking is a vicious habit with systemic and local complications. Special measures have to be taken, mostly related to a delayed healing of the soft tissue, the decreased resistance to inflammation of the gums and tissues around the implant and decreased resistance to infection after any oral surgery. Depending on the type of systemic pathology, the special precautions needed to be taken in HCP are the following: Conclusions It is mandatory to know the implications of the systemic diseases or those produced by current medications in the oral cavity, in order to prevent failures in HCP patients who receive dental implant therapy. Given the altered biological constants of the patient, the medical team must be able to solve any complication that occurs and should also be prepared with more treatment options for that situation. Systemic conditions and treatments as risks for implant therapy. Page 2

3 Int J Oral Maxillofac Implants. Dental implant placement in type II diabetics: J Mass Dent Soc. Javed F, Romanos GE. Impact of diabetes mellitus and glycemic control on the osseointegration of dental implants: Impact of systemic diseases and medication on osseointegration. A systematic review on the association between genetic predisposition and dental implant biological complications. Clin Oral Implants Res. Mombelli A, Cionca N. Systemic diseases affecting osseointegration therap. Review of dental implant rat research models simulating osteoporosis or diabetes. Outcome of implant therapy in patients with previous tooth loss due to periodontitis. An insight into peri-implantitis: Effects of radiation therapy on craniofacial and dental implants: Differential diagnosis and treatment strategies for biologic complications and failing oral implants: Dental endosseous implants in the medically compromised patient. Risk factors for osseodisintegration. Dental implant considerations in the diabetic patient. Retzepi M, Donos N. Page 3

4 Chapter 2 : Implant surgery in healthy compromised patients-review of literature null. Increased risk of infection associated with periodontal disease in immunocompromised patients. Underlying periodontal disease can affect the successful outcome of an organ transplant via direct and indirect pathways. None, Conflict of Interest: Consequently, many of these patients are now seeking orthodontic therapy. This article will discuss various systemic diseases, their effect on orthodontic treatment and the recommended methods to avoid the potential problems that may arise. Guidelines, interdisciplinary management, life expectancy, medically compromised patient, orthodontic considerations, orthodontic treatment How to cite this article: Orthodontic care of medically compromised patients. Indian J Oral Sci ;3: This article examines aspects of some of the conditions that are of relevance to orthodontic practice. Medical conditions commonly encounter in orthodontic patients include; Infective Endocarditis Bacterial endocarditis is a relatively uncommon, life-threatening infection of the endothelial surface of the heart, including the heart valves. It can occur whenever these persons develop bacteremia with the organisms likely to cause endocarditis. Both the incidence and the magnitude of bacteremias of oral origin are proportional to the degree of oral inflammation and infection. Informed consent requires that a patient is aware of any significantly increased risk. The main orthodontic procedure that has been postulated to cause a bacteraemia has been placement of a separator. If banding is required use of antibiotic prophylaxis is must. Lengthier the treatment duration may increase potential complications. Fixed appliances are preferable to removable appliances as the latter can cause gingival irritation. If conventional brackets are used, archwires should be secured with elastomeric modules instead of wire ligatures. Cranial irradiation given to children with acute lymphocytic leukemia ALL to eliminate cancer cells in the central nervous system CNS can cause growth retardation, most probably through its effect on pituitary function, specifically growth hormone deficiency. Arrested root development with short V-shaped roots and premature apical closure has been reported after cancer therapy. Minor irritation can lead to opportunistic infection and subsequent severe complications. Use appliances that minimize the risk of root resorption, Use lighter forces, terminate the treatment earlier than normal, choose the simplest method for the treatment needs and do not treat the lower jaw. A group of patients who developed ORN of the jaws were reviewed and treated between and The most common affected site was the mandible 99 cases, Among all cases, 93 In adults receiving head and neck radiotherapy the incidence of ORN is 8. Thalassemia Thalassemia is an inherited disorder of hemoglobin synthesis. The most common oral and facial manifestation is enlargement of the maxilla, bossing of the skull and prominent malar eminences due to the intense compensatory hyperplasia of the maxilla. This lead to expansion of the marrow cavity and a facial appearance known as "chipmunk" face. Antibiotic of choice is penicillin V mg or erythromycin mg taken 30 min to 2 h prior to dental procedure, then mg taken every 6 h for 8 doses. Regular prophylaxis and fluoride applications are recommended in these patients. Extraction should be carried out at the time of admission for blood transfusion, i. Bronchial Asthma Asthma is a chronic disease that affects the lower airways. It is characterized by recurrent and reversible airflow limitation due to an underlying inflammatory process. Orthodontics considerations Inhaled corticosteroids are the most widely used and most effective asthma anti-inflammatory agents. Judicious use of rubber dams should be avoided as they reduced breathing capability. Care should be used in the positioning of suction tips as they may elicit a cough reflex. The orthodontist should ensure the patient has their inhaler nearby. Epilepsy Epilepsy is the most common serious chronic neurological condition. It is as a chronic neurological disorder characterized by frequently recurrent seizures. It affects about 0. Gingival overgrowth associated with phenytoin is the most widely known complication of anti-epileptic medication. Gingivectomy is recommended to remove any hyperplasic tissue that interferes with appearance or function. Removable appliances should be used with caution as they can be dislodged during a seizure. The metal in a fixed orthodontic appliance may distort images obtained by magnetic resonance imaging MRI. Diabetes Mellitus DM is one of the most common endocrine disorders. It is characterized by persistently Page 4

5 raised blood glucose levels hyperglycemia, resulting from deficiencies in insulin secretion, insulin action, or both. Orthodontic considerations The key to any orthodontic treatment for a patient with diabetes is good medical control. Orthodontic treatment should not be performed in a patient with uncontrolled diabetes. Diabetic related microangiopathy can affect the peripheral vascular supply, resulting in unexplained toothache, tenderness to percussion and even loss of vitality. Apply light forces and not to overload the teeth. Uncontrolled or poorly controlled diabetic patients have an increased tendency for periodontal breakdown and these patients should be considered in the orthodontic treatment plan, as periodontal patients. Renal Disorders The most common renal condition to present to the orthodontist is chronic renal failure. Chronic renal failure is a progressive and irreversible decline in renal function. Initially treatment is conservative with dietary restriction of sodium, potassium and protein. As the disease progresses dialysis or transplantation are required. Many patients are prescribed steroids to either combat renal disease or to avoid transplant rejection Orthodontic considerations Extraction should be done cautiously in such patients. Abnormal bone healing after extraction can result due to alterations in calcium and phosphors metabolism and secondary hyperparathyroidism which result in bone demineralization. It has been suggested that orthodontic treatment forces should be reduced and the forces re-adjusted at shorter intervals. Renal insufficiency is considered a risk condition for IE if the patient does not have a good control of the disease. For this reason, dental treatments with a risk of bleeding must not be performed on the day of hemodialysis. Appointments should be scheduled on non-dialysis days. The day after dialysis is the optimum time for treatment for surgical procedures as platelet function will be optimal and the effect of heparin will have worn off. Many antibiotics are actively removed by the kidney, so adjustment of the dosage by amount or by frequency is required. In the case of non-narcotic analgesics, paracetamol is the best choice. In renal transplant patients corticosteroid are given to minimize the risk of transplant failure. In such patients to minimize the risk of adrenal crisis in patients during surgical procedure, double the dose of corticosteroids on the day of the surgery. Nifedipine increases the prevalence of gingival overgrowth. Gingivectomy should be considered in such patients. Osteoporosis Osteoporosis is chronic, systemic, degenerative disease characterized by decreased bone mass, a micro architectural deterioration of the bone and consequent increase in bone fragility. Orthodontic considerations Orthodontic treatment therefore, must include the consideration of problems such as bone loss, retention instability, and temporomandibular dysfunction. Estrogen decreases the rate of tooth movement. Use of BP can affect orthodontic treatment by delaying tooth eruption, inhibited tooth movement, [47] impaired bone healing, and by causing BP-induced ORN of the jaws. Extraction protocol and use of temporary anchorage devices should be avoided. Orthodontic considerations Orthodontic therapy requires minimal alterations in the patient with adequately managed thyroid disease. In hyperthyroidism enlarged tongue may pose problem during treatment. The bone turnover can influence orthodontic treatment. High bone turnover i. Low bone turnover i. The liver has a broad range of functions in maintaining homeostasis and health: HBV, hepatitis C virus, and hepatitis D virus are blood borne and can be transmitted via contaminated sharps and droplet infection. Aerosols generated by dental hand pieces could infect skin, oral mucous membrane, eyes or respiratory passages of dental personnel. The main orthodontic procedures to result in aerosol generation are removal of enamel during interproximal stripping, removal of residual cement after debonding, and prophylaxis. Barrier technique such as gloves, eye glasses, and mouth mask should be used. HBV can survive on innate subjects for 7 days. Impressions can be one of the links in transmitting the HBV to orthodontics. The impressions must be disinfected by dipping them in glutaldehyde or by spraying sodium hypochlorite and leaving it for 10 min. If extraction is required, special attention should be paid as the risk of bleeding increases; an infusion of fresh frozen plasma may be indicated. Advanced oral surgical procedures or any dental procedures with the potential to cause bleeding performed on a patient with multiple or a severe single coagulopathy may need to be provided in a hospital setting. Hepatic impairment can lead to failure of metabolism of some drugs and result in toxicity. He was then termed the "father" of the syndrome. The bridge of the nose, bones of the midface and maxilla are relatively smaller in size. There is usually some sort of Page 5

6 enamel defect affecting the teeth. There is usually congenitally missing teeth and they can have unusually shaped teeth. Children with heart defects who are undergoing dental procedures should be given antibiotic prophylaxis against subacute bacterial endocarditis. More food may remain on the teeth after eating due to this inefficient chewing. It is ensure that patient is vaccinated for hepatitis before starting dental treatment. This is necessary because persons with Down syndrome are at increased risk of developing the carrier state if they are infected with HBV. Seizures are diagnosed and treated similarly in children with and children without Down syndrome. Impressions using quick-set materials with fun flavors should be used as these may reduce the tendency for activation of the more sensitive gag reflex frequently experienced with Down syndrome patients. High-memory wires allow a longer activation interval between appointments. Page 6

7 Chapter 3 : Candida Infection - The Oral Cancer Foundation Periodontal Implications: Medically Compromised Patients., Relationship between oral bacteria and hemodialysis access infection, Oral Surgery. Yeasts have become increasingly significant as pathogens in all fields of medicine. Fungi are part of the world of plants, not bacteria, and there are about, distinct types of them. In people they are common, and usually harmless companions of our skin tissues, and live as inhabitants of our mucous membranes in our mouth, vaginal tract etc. Yeast infections such as Candida were recognized centuries ago as an indicator of much larger underlying diseases such as diabetes mellitus, malignant tumors, and chronic infections. Sort of the miners canary. When antibiotics are used, there is a flip-flop in the balance of the natural occurring flora in the mouth and elsewhere where the normal flora is damaged by the antibiotic therapy to the advantage of the fungus, which then blooms. Damage to the mucus membranes and to the salivary glands also allow for Candida colonization. Dry mouth xerostomia, upsets the balance of microorganisms in the oral cavity. When the delicate balance of normal and abnormal bacteria is disturbed, an overgrowth of this fungus may occur. At this late stage it can be deadly. Left unchecked by antifungal drugs it can actually become several millimeters thick. The whitish portion is not firmly attached to the underlying tissue, and can actually be wiped or brushed off. Candida is commonly called thrush, and if left unchecked for a period in the mouth, it can spread to the pharynx and the esophagus and cause severe symptoms such as erosions and ulcerations of the tissues. Doctors can typically diagnose Candidiasis simply by looking in the mouth or the back of the throat, but a sampling of the white overgrowth may be scraped easily from the surface and sent to a lab for positive identification. Classic symptoms of oral Candidiasis include the appearance of whitish, velvety plaques on the mucous membranes of the mouth and tongue. If the whitish material is scraped away, the base may be red erythematous with pinpoint bleeding. More general symptoms of candida infection include burning pain in the mouth or throat, altered taste especially when eating spicy or sweet foods, and difficulty swallowing. The corners of the mouth may also become chapped, cracked, and sore angular cheilitis. If the immune system has been severely compromised, the infection may cover much of the surface of the mouth and tongue, and it may spread to the esophagus. Esophageal candidiasis, which is much more common in people with suppressed immune systems, occurs deep in the throat, and cannot always be seen during an oral examination. An endoscope is commonly used to identify this type of Candidiasis. In its esophageal form, Candidiasis can cause chest pain, as well as pain and difficulty in swallowing. Once the Candida fungus migrates past the gastrointestinal tract, it can become established in other major organs such as the lungs and kidneys. Left untreated, it can even cause death. When Candida progresses to the point where it is in the bloodstream, it is referred to as Candida sepsis. At this stage it is hard to treat and recovery is extremely difficult. The death rate from late stage disseminated Candidiasis may reach seventy percent. The importance of treating it in its early stages cannot be overstated. This condition occurs when the wall of the gastrointestinal tract is damaged. The Candida change form, creating rhizoids, root like structures that break the intestinal walls. A healthy intestinal wall will allow only nutrients to enter bloodstream, but when it is damaged, larger molecules such as incompletely digested fats, proteins, and toxins may also slip through. The body recognizes these substances as foreign and forms antibodies to them, causing the patient to suddenly become allergic to foods they would previously been able to eat without a problem. LGS may also lead to environmental allergies, causing the patient to respond to inhalants in their general environment. With LGS, vitamin and mineral deficiencies are common because the patient lacks the ability to move minerals and vitamins from the gut to the blood. When the Candida becomes controlled and the gut has healed, food allergies will remain until antibodies to that food have been eliminated. Antifungal agents are vital to the control of candidiasis. These can be either systemic or topical. Topical antifungal agents include nystatin and clotrimazole or other closely related agents, either of which may be applied directly to the oral lesions as a dissolving lozenge or in a liquid wash. Infections that are Page 7

8 resistant to those agents, or that have already disseminated, are treated with IV medications such as Amphotericin B, Ketoconazole, Itraconazole, and some oral antifungal agents such as Fluconazole Diflucan. These are more potent drugs, and are more likely to cause side effects, including stomach upset, diarrhea, nausea, and elevated liver enzymes. These health store remedies are not as potent as prescription medication, and may not be as effective for those who have had radiation therapy or chemotherapy. One of these types of treatments is gentian violet, a dye made from coal tar that may be purchased from some pharmacies, health food stores, and other places where alternative therapies are sold. The dye is applied by using a cotton swab to coat the Candida blotches. It is best to avoid swallowing the dye, as it can cause upset stomach. Gentian violet can also stain the inside of the mouth, but this fades over time. Though potentially serious, prescription antifungal agents can quickly eradicate a Candida infection. Page 8

9 Chapter 4 : Oral Manifestations of HIV Pneumocystis pneumonia (PCP) is a serious infection that causes inflammation and fluid buildup in your lungs. It's caused by a fungus called Pneumocystis jiroveci that's likely spread through the air. Patients with hematologic malignancies and hematopoietic stem-cell transplants are at high risk for fatal invasive fungal infections. In this patient subpopulation, fungal infections are commonly caused by Candida and Aspergillus species, and if not managed properly, they can result in significant mortality and morbidity. In order to prevent such infections, prophylactic antifungal drug therapy is recommended for patients with poor immune function. Certain medications from the azole and echinocandin drug classes are considered first-line agents for prophylaxis. While these agents are highly efficacious, pharmacokinetic properties and adverse-effect profiles should be considered for optimal therapeutic outcomes. In addition to other health issues, patients with immune-system defects are at high risk for invasive fungal infections. Immunocompromised states in which such fungal infections commonly occur include Table 1 hematologic malignancies leukemia, myelodysplastic syndrome ; severe neutropenia; mucositis in autologous hematopoietic stem-cell transplants HSCT ; and significant graft-versus-host disease GVHD. Subsequently, the pathogens enter the circulation, resulting in candidemia, a serious blood-borne infection. Inhalation of Aspergillus fumigatus, on the other hand, affects the lung cells and is followed by pneumonia. Other manifestations of Aspergillus infections include sinusitis, cerebral infarction, and skin ulcers. It is currently believed that prophylaxis in immunocompromised patients can markedly reduce the number of deaths and serious complications associated with fungal infections. Hence, antifungal prophylaxis is continued until the neutrophil count is restored. For optimal therapeutic management, other properties of individual therapeutic agents need to be taken into account, as discussed below. First-Line Agents Fluconazole and Posaconazole: These azoles are generally well tolerated. However, use of both agents is associated with liver toxicity reversible elevation of liver enzymes and electrocardiographic abnormality prolongation of QTc interval. For better absorption, posaconazole solution should be taken with a full meal. Proton pump inhibitors decrease plasma levels of posaconazole when administered as an oral solution. This echinocandin, like other members of this class, does not induce or inhibit CYP enzymes, nor does it interact with P-glycoprotein. As a result, the potential for drug interactions with other therapeutic agents is negligible. Micafungin is well tolerated, and the most common adverse reactions include histamine-mediated effects rash, pruritus, facial swelling, GI distress, headache, and pyrexia. This azole, a second-line prophylactic agent, is minimally bound to plasma protein. Voriconazole is excreted by the kidney. Transient visual disturbances blurred vision, changes in color vision or brightness, bone pain, and squamous cell cancer are significant adverse reactions associated with its use. Amphotericin B is a broad-spectrum polyene antifungal agent. Its use is associated with two major adverse effects: For antifungal prophylaxis, the lipid formulations liposomal amphotericin B and amphotericin B lipid complex are used to minimize such adverse reactions. With the exception of C krusei, fluconazole treatment prevented infections with other Candida strains. Fluconazole treatment caused a mean increase in the liver enzyme alanine aminotransferase; otherwise, the drug therapy was well tolerated. Superficial fungal infections, fungal colonization, and empiric antifungal therapy requirements with amphotericin B were also markedly reduced as a result of fluconazole prophylaxis. The incidence of GVHD in the gut and deaths from complications were also found to be lower in patients receiving fluconazole prophylaxis. In a multicenter, double-blind trial, patients aged 18 to 80 years of both genders undergoing cytotoxic chemotherapy for leukemia or autologous bone marrow transplant received daily oral treatment of mg fluconazole until neutropenia was resolved for 2 days, parenteral amphotericin B therapy was initiated, or a maximum duration of 60 days was reached. Patients who were treated with a cytarabine-plus-anthracycline combination or who received an autologous stem-cell transplant and were not treated with any colony-stimulating growth factor received the most benefit from this intervention. Cornely and colleagues compared posaconazole prophylaxis Page 9

10 with that of fluconazole or itraconazole in neutropenic patients suffering from acute myeloid leukemia AML or myelodysplastic syndromes who were receiving induction or reinduction chemotherapy. Posaconazole recipients had a longer survival period than fluconazole or itraconazole recipients. However, serious adverse events occurred more often in posaconazole-treated patients as opposed to the fluconazole or itraconazole group. In a randomized, double-blind, multicenter, phase III trial, micafunginâ an echinocandinâ was compared with fluconazole for antifungal prophylaxis in patients who underwent hematopoietic stem-cell transplantation. Treatment success was determined to be the absence of systemic fungal infections throughout the entire prophylactic period and the absence of systemic fungal infection until the end of 4-week postprophylactic therapy. The most frequent adverse effect observed in both treatment arms was abnormal liver parameters. Although no difference was noted in the primary endpoints, patients in the voriconazole-treated group displayed a declining trend in Aspergillus infections, invasive fungal infections, and the requirement of empirical antifungal treatment. Adverse drug reactions were equivalent in both treatment groups. There was a declining trend of lung infiltrate in voriconazole-treated patients. At 4-week follow-up, hepatosplenic candidiasis was reported in patients belonging to the placebo group; none was reported in the voriconazole-treatment group. The drug therapy was well tolerated by the patients. There were significantly fewer invasive pulmonary aspergillosis cases in patients who received amphotericin B inhalation. Coughing was the most frequent adverse effect from amphotericin B treatment. Hypokalemia was reported in six patients, but nephrotoxicity was absent. In one patient, drug therapy was discontinued for infusion-related infections. Findings indicated there was no significant difference in fungal infections, survival, or death. Another important role of the pharmacist is to periodically monitor organ functions, particularly those of the liver for azoles and kidneys for amphotericin B. Also, as treatment guidelines continue to change, pharmacists need to keep abreast of medical literature to enhance knowledge and competence. According to the current literature, the occurrence of systemic fungal infections can be successfully prevented by proper and timely use of effective antifungal agents. Individualized therapeutic monitoring for drug efficacy and safety are equally important parameters for successful treatment outcomes. Clinical pharmacists have been instrumental in fulfilling such crucial tasks. Prevention and treatment of cancer-related infections, Version 2. J Natl Compr Canc Netw. Sheppard D, Lampiris HW. Basic and Clinical Pharmacology. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantationâ a prospective, randomized, double-blind study. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis related death in allogeneic marrow transplant recipients: Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. A double-blind trial on prophylactic voriconazole VRC or placebo during induction chemotherapy for acute myelogenous leukaemia AML. Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: Prospective phase II single-center study of the safety of a single very high dose of liposomal amphotericin B for antifungal prophylaxis in patients with acute myeloid leukemia. Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation. To comment on this article, contact rdavidson uspharmacist. Page 10

11 Chapter 5 : Antifungal Prophylaxis for Immunocompromised Patients The topics to be covered include odontogenic orofacial "space" infections; suppurative parotitis; peritonsillar abscess; and deep neck space infections, including submandibular (Ludwig's angina), lateral pharyngeal, and retropharyngeal space infections. Early recognition, diagnosis, and treatment of HIV-associated oral lesions may reduce morbidity. This chapter is an overview of oral lesions most frequently associated with HIV disease Table 1. A number of factors predispose patients to develop candidiasis: Candidiasis is a common finding in people with HIV infection. Several reports indicate that most persons with HIV infection carry a single strain of Candida during clinically apparent candidiasis and when candidiasis is quiescent. The most common presentations include pseudomembranous and erythematous candidiasis, which are equally predictive of the development of AIDS, 12 and angular cheilitis. These lesions may be associated with a variety of symptoms, including a burning mouth, problems eating spicy food, and changes in taste Figure 1, Figure 2. All three of these common forms may appear in one individual. Pseudomembranous Candidiasis Thrush Characteristic creamy white, removable plaques on the oral mucosa are caused by overgrowth of fungal hyphae mixed with desquamated epithelium and inflammatory cells. The mucosa may appear red when the plaque is removed. This type of candidiasis may involve any part of the mouth or pharynx. Erythematous Candidiasis Erythematous candidiasis appears as flat, red patches of varying size. It commonly occurs on the palate and the dorsal surface of the tongue. Erythematous candidiasis is frequently subtle in appearance and clinicians may easily overlook lesions, which may persist for several weeks if untreated. Angular Cheilitis Angular cheilitis appears clinically as redness, ulceration, and fissuring, either unilaterally or bilaterally at the corners of the mouth. It can appear alone or in conjunction with another form of candidiasis. The lesions appear white and hyperplastic. The white areas are due to hyperkeratosis and, unlike the plaques of pseudomembranous candidiasis, cannot be removed by scraping. These lesions may be confused with hairy leukoplakia. Diagnosis of hyperplastic candidiasis is made from the histologic appearance of hyperkeratosis and the presence of hyphae. Periodic acid-schiff PAS stain is often used to demonstrate hyphae. Histologically, oral candidiasis contains Candida hyphae in the superficial epithelium when viewed under a PAS stain. The inflammatory responses often associated with Candida infection may be absent in immunocompromised patients. The creamy white plaques of pseudomembranous candidiasis are removable; the white lesions of hairy leukoplakia are nonremovable. Diagnosis Candida is a commensal organism in the oral cavity. Candidiasis is diagnosed by its clinical appearance and by detection of organisms on smears. Smears are taken by gently drawing a wooden tongue depressor across the lesion. The specimen is then transferred into a drop of KOH on a glass slide and protected by a cover slip. The smear is examined under the microscope and Candida is detected by finding hyphae and blastospores. Hyphae and spores are only seen in smears from lesions and are rarely seen in the healthy individual in the carrier state. This probably represents a carrier state rather than active infection. Treatment Oral candidiasis may be treated either topically or systemically. Response to treatment is often good; oral lesions and symptoms may disappear in a fairly short period ranging from 2 to 5 days, but relapses are common because of the underlying immunodeficiency. As with other causes of oral candidiasis, recurrences are common if the underlying problem persists. Topical Treatment Topical treatments are preferred because they limit systemic absorption, but the effectiveness depends entirely on patient compliance. Topical medications require that the patient hold medications in the mouth for 20 to 30 minutes. If the patient uses formulations containing sweetening agents for long periods, consider as concurrent treatment daily fluoride rinses e. Clotrimazole is an effective topical treatment one oral troche [mg tablet] when dissolved in the mouth five times daily. Used less frequently, one vaginal troche can be dissolved in the mouth daily. Nystatin preparations include a suspension, a vaginal tablet, and an oral pastille. Regimens are nystatin vaginal tablets one tablet,, units, dissolved in the mouth three times a day, or nystatin oral pastille available as a,unit Page 11

12 oral pastille, one or two pastilles dissolved slowly in the mouth five times a day. Nystatin suspension has a high sugar content and cannot be held in the mouth long enough to be effective. Topical creams and ointments containing nystatin, ketoconazole, or clotrimazole may be useful in treating angular cheilitis. Another therapeutic choice is amphotericin B 0. Five to 10 ml of oral solution is used as a rinse and then expectorated three to four times daily. Systemic Treatment Several agents are effective for systemic treatment. Ketoconazole Nizoral is a mg tablet taken with food once daily. Patient compliance is usually good. Careful monitoring of liver function is necessary for long-term use because of reported side effects, including hepatotoxicity. Lack of efficacy of ketoconazole may occur because of poor absorption in those with an abnormally high gastric ph. Fluconazole Diflucan is a triazole antifungal agent effective in treating candidiasis mg tablet taken once daily for 2 weeks. Numerous reports, 16 however, describe oral and esophageal candidiasis failing to respond to treatment with fluconazole, and in some of these cases investigators isolated resistant strains. Salivary levels of itraconazole are maintained for several hours after administration. Ketoconazole, fluconazole, and itraconazole may interact with other medications including rifampicin, phenytoin, cyclosporin A, terfenadine, digoxin, coumarin-like medications, and oral hypoglycemic medications. Prognostic Significance Both erythematous and pseudomembranous oral candidiasis are associated with increased risk for the subsequent development of opportunistic infections classifying the patient as having AIDS as defined by the Centers for Disease Control CDC. These lesions appear as ulcerations that can affect any mucosal surface. Cryptococcus Neoformans A report described Cryptococcus neoformans causing an ulcerated mass in the hard palate of a patient with a previous history of Pneumocystis carinii pneumonia. A biopsy of the palatal ulcer made the diagnosis. Primary herpetic gingivostomatitis commonly occurs in children and young adults and may be followed by frequent recurrences. Following the primary episode, the virus becomes latent in the trigeminal ganglion. Recurrent oral herpes occurs at any age extraorally or intraorally. Clinical Features Recurrent herpes labialis occurs on the vermilion border of the lips. The patient may report a history of itching or pain, followed by the appearance of small vesicles. These rupture and form crusts. Recurrent intraoral herpes appears as clusters of painful small vesicles that rupture and ulcerate and usually heal within 1 week to 10 days. The lesions usually occur on the keratinized mucosa, such as the hard palate and gingiva, although lesions may arise on the dorsal surface of the tongue. Differential Diagnosis Rising antibody titers from initial and convalescent sera confirm primary herpetic gingivostomatitis. Examining smears of lesions treated with Papanicolaou stain for multinucleated giant cells confirms recurrent herpes. It is possible to demonstrate herpes simplex type 1 or type 2 by applying monoclonal antibodies to smears from the lesions the Syva Kit, Syva Corporation, Palo Alto, CA. Clinicians can distinguish between recurrent intraoral herpes simplex lesions, which always occur on keratinized mucosa such as the hard palate and gingiva, and recurrent aphthous ulcers, which always appear on nonkeratinized mucosa. Recurrent intraoral herpes may appear more frequently in HIV-infected patients. The lesions may be painful and slow to heal. Treatment No treatment will permanently eradicate oral herpes simplex infections, but acyclovir may shorten the healing time for individual episodes. The optimum oral dosage of acyclovir is 1, to mg daily for 7 to 10 days. Topical acyclovir is not useful for treating intraoral lesions and may not be effective for lesions on the lips. Recurrent outbreaks of acyclovir-resistant herpes have been reported, including a case involving the facial skin, lips, nose, and mouth. In this case, the lesions resolved after treatment with foscarnet. Prognostic Significance There is no known association between recurrent intraoral herpes and more rapid progression of HIV disease. However, there is a clinical impression that recurrent herpes simplex infections may be more common in patients with symptomatic HIV disease. The disease occurs in the elderly and the immunosuppressed. Clinical Features Oral herpes zoster generally causes skin lesions. Following a prodrome of pain, multiple vesicles appear on the facial skin, lips, and oral mucosa. The skin lesions form crusts and the oral lesions coalesce to form large ulcers. The ulcers frequently affect the gingiva, so tooth pain may be an early complaint. Differential Diagnosis The appearance of the lesions and their distribution are pathognomonic. Treatment Acyclovir limits the duration of the lesions. For herpes zoster, the standard oral Page 12

13 dosage is mg five daily for 7 to 10 days, which is considerably higher than that recommended for treatment of herpes simplex. Human Papillomavirus Lesions Oral warts, papillomas, skin warts, and genital warts are associated with the human papillomavirus HPV. Anal warts have frequently been reported among homosexual men. Because the HPV types found in oral lesions in HIV-infected persons are different from the HPV types associated with anogenital warts, clinicians should probably not use the term condyloma acuminata to describe oral HPV lesions. Clinical Features HPV lesions in the oral cavity may appear as solitary or multiple nodules. They may be sessile or pedunculated and appear as multiple, smooth-surfaced raised masses resembling focal epithelial hyperplasia or as multiple, small papilliferous or cauliflower-like projections Figure 3. I have identified HPV types 7, 13, and 32 in some of these oral warts. Differential Diagnosis A biopsy is necessary for histologic diagnosis. Prognosis There is no known association between oral HPV lesions and more rapid progression of HIV disease, but oral warts are seen more commonly in HIV-infected persons than in the general population. Treatment Oral HPV lesions can be removed surgically using local anesthetic. Carbon dioxide laser surgery can remove multiple flat warts, but relapses occur and several repeat procedures may be necessary. Cytomegalovirus Oral ulcers caused by cytomegalovirus CMV have been reported. Unlike aphthous ulcers, however, which usually have an erythematous margin, CMV ulcers appear necrotic with a white halo. Page 13

14 Chapter 6 : Cancer Patients and Fungal Infections Fungal Diseases CDC While they are not common, we have documented oral CMV infections in CMV(c) patients during the early post-transplant stages [23, 25, 30, 33, 34]. ShareCompartir As a cancer patient, you may have received a lot of information about your treatment and your journey to recovery. Chemotherapy and radiation cause many changes in the body as they destroy cancer cells. One major change is that these treatments weaken your immune system, which can increase your chances of getting an infection, including a fungal infection. Stem cell transplant patients or those who have a blood hematologic cancer such as leukemia, lymphoma, or myeloma may have different risks for fungal infections. What you need to know about fungal infections Chemotherapy and radiation lower your white blood cell count. As you receive your cancer treatment, your white blood cell count can become very low, also known as neutropenia [PDF - 2 pages]. During this time, your body will have trouble fighting infections, including fungal infections. Some fungal infections are mild skin rashes, but others can be deadly, like fungal pneumonia. Fungal infections can look like bacterial or viral infections. The type of cancer you have can affect your risk. If you have a blood cancer like leukemia or myeloma, you may be at greater risk for getting a fungal infection than people with other types of cancer. Some types of cancer may require stronger chemotherapy medication than others, especially the blood cancers. This is sometimes known as aggressive chemotherapy. Aggressive chemotherapy weakens your immune system and can put you at risk for getting a fungal infection. After your transplant, you may need to stay in the hospital for a long time. While there, you may need to have procedures that can increase your chance of getting a fungal infection. Please see types of healthcare-associated infections for more information. Where you live geography matters. Some disease-causing fungi are more common in certain parts of the world. If you live in or visit these areas and have cancer, you may be more likely to get these infections than the general population. Top of Page Preventing fungal infections in cancer patients Fungi are difficult to avoid because they are a natural part of the environment. Fungi live outdoors in soil, on plants, trees, and other vegetation. They are also on many indoor surfaces and on your skin. However, there may be some ways for you to lower the chances of getting an infection, including a serious fungal infection. Learn about fungal infections. There are different types of fungal infections. Learning about them can help you and your healthcare provider recognize the symptoms early, which may prevent serious illness. Know if your white blood cell count is low. Having a very low white blood cell count neutropenia [PDF - 2 pages] can put you at greater risk of infection. Fungal infections often resemble other illnesses. Visiting your healthcare provider may help with faster diagnosis and may prevent serious illness. Your healthcare provider may prescribe medication to prevent fungal infections. Scientists are still learning about which patients are at highest risk and how to best prevent fungal infections. As you recover from chemotherapy and start doing your normal activities again, there may be some ways to lower the chances of getting a serious fungal infection by trying to avoid disease-causing fungi in the environment. Try to avoid areas with a lot of dust like construction or excavation sites. Stay inside during dust storms. Stay away from areas with bird and bat droppings. This includes places like chicken coops and caves. Wear gloves when handling materials such as soil, moss, or manure. Wear shoes, long pants, and a long-sleeved shirt when doing outdoor activities such as gardening, yard work, or visiting wooded areas. Click here to read more about preventing infections in cancer patients. Fungal infections in cancer patients: Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients. Journal of Antimicrobial Chemotherapy ; Fungal infections and the cancer patient. European Journal of Cancer ;33, Supplement 4: Fungal infections in immunocompromised travelers. Clinical Infectious Diseases ; Annals of Hematology ; Recommendations and Reports ; Page 14