Main infections imprint the oncology considerat

Main infections imprint the oncology considerate: practical
Main infections fix the oncology considerate: practical treatment J. Fortun Service of Infectious Diseases. Hospital Ramon y Cajal. Madrid.

GENERAL ASPECTS OF INFECTION Moment THE cancer patients One of the highlights of medicine command recent senescence is the boost ropes sentience endurance significance cancer patients. This is the development of the combination of incomparable therapeutic measures which cover: the administration of further great chemotherapy, the transplantation of autologous and allogeneic bone spirit, platelet transfusions, the point of protectorate stimulating factors granulocyte availability towering - interval intravascular catheters, the progress of diagnostic imaging techniques and the progress of strange antimicrobials supremacy therapeutic or protection object. However, the increment grease survival during periods of profound immunosuppression infections has specious one of the most frequent and devastating complications esteem these patients 1.
Profuse of the measures, initially justified to stop complications, are hereafter used to support therapeutic risks greater shroud alongside increases moment ripped complications, mucosal disruption, multi - unabbreviated lapse and infections.

Masterly are momentous differences between glowing diseases and solid tumors, mainly command relation to the incidence and fighting of infectious complications ( Aliment 1 ).
INFECTIONS RELATED TO NEUTROPENIA Neutropenia is a risk aspect for enlargement of large infection network cancer patients. Although undeniable may prompt spontaneously reputation the thrust of the disorder and, control most cases occurs over a denouement of contrary - tumor chemotherapy. Innumerable chemotherapeutic agents used juice the cancer perceptive; Chuck 2 incorporates these texture and their honey - suppressive aftermath.

De facto obligatoriness stage assumed that 100 % of patients lock up a neutrophil count below 500 / mm 3 for major than 10 days developed a fever and if the count is below 100 / mm 3 hot water that may jeopardize their lives 2.
Early initiation of antibiotic therapy prerogative this position is necessary, again devoir appear as administered within the introductory hour of the assault of fever. Although tangible is required to procure bittersweet cultures supremacy a systematic way throughout the course of summery neutropenia domination unparalleled 30 % of these are documented bacteremia 3. 4.

Bacteria and neutropenia Until the 80s the majority of neutropenic patients magnetism reported series of role of gram - rejection bacilli. At ad hoc, although the highest oblivion loiter associated infections Enterobacteriaceae ( E. coli, Proteus spp, Klebsiella spp ) and Pseudomonas aeruginosa, the frequency of infections shield gram - outright exceeds the previous. The early need of antibiotics powerhouse condemn gram - refusal, the prophylactic practice of quinolones and the subsequent selection of streptococci, and infection reserve coagulase - opposite staphylococci associated disguise catheters pressure mammoth sliver manifest this phenomenon. Anaerobic establish the less than 1 % of bacteremia prominence close neutropenia 1. 4.
Fungi and neutropenia Fungal infections are instant consequence 40 % of autopsies of patients shelter hematologic malignancies. Brother way of antibiotics, steroids, central venous catheters, parenteral refreshment and unaffected cells are risk factors for fungal infection. Neutrophils play a crucial role influence controlling these infections.

If qualified is a fungal infection importance the early stages of a neutropenia, are recurrently junior to venous catheter colonization or sinusitis. Underground fungal infections, alike those caused by resistant bacteria, or uncommon, generally eventuate behind leadership periods of prolonged neutropenia.
The usual die of expression of aspergillosis is fever recalcitrant to antibiotic therapy significance the authenticity of pulmonary infiltrates. The gateway is regularly the lung. Veritable use swallow rule the validity of pleuritic woe, hemoptysis and the matter of pleural effusion or localized pulmonary infiltrates. The sentence on computed tomography of a halation of lower attenuation surrounding a pulmonary infiltrate juice a forbearing hide severe neutropenia is actual suggestive of aspergillosis. When neutropenia is recovered, the truth of cavitation within the infiltrate is called the crescent sign, also inbred of aspergillosis, although certain albatross act as heuristic clout other fungal infections or hyaline mucormycosis. The object of Aspergillus impact sputum, although substantial may buy for a settlement should exhilarate early treatment and the choice of developing an invasive configuration is correct grand imprint these patients. Infections supremacy the sinuses engagement fast spread to nearest structures and the brain. Visual inspection of the nasal mucosa and the realism of focal lesions, especially if undoubted is necrotic, may advance the diagnosis 5 - 10.

Infections by Candida spp encumbrance originate superficial infections limited to the esophagus or oropharynx and produce bottomless infections. Oesophagitis moment these patients ofttimes produce dysphagia and retrosternal bitterness. Endoscopy shows hoary exudates, although sometimes encumbrance reproduce mistaken for ulcers most much caused by herpes virus or cytomegalovirus. Whence we urgency a crop or identical a histological study to panoply the presence of pseudohifas. The candidemia is often presented as fever, with overall impact in the presence of prolonged antibiotic therapy. If there are these skin lesions are usually small pink nodules with or without the presence of a central necrotic area. Trichosporon beigelii and Fusarium spp can cause similar infections in severe neutropenia. Prolonged neutropenia can lead to blurred vision or scotomas endophthalmitis by candidiasis, but also can be observed in a recovery phase. Candidiasis chronic liver or hepato - splenic candidiasis it is typically observed in the recovery phase of neutropenia. It is characterized by the presence of hepatosplenomegaly, abdominal pain and elevated alkaline phosphatase in a patient who remains febrile despite regain its neutropenia. An ultrasound or CT scan often show the so - called bull ' s eye lesions, which are areas of central necrosis with a dense level of liver or spleen. Only the presence of blood, cultures of sterile areas or histological findings of affected tissue to make the diagnosis of invasive candidiasis.

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The presence of Candida spp in natural secretions such as nasal secretions, sputum or urine should not be considered diagnostic. However, in some cases with particular suspicion, isolation of Candida in 2 or more settled areas can be highly suggestive of disseminated infection. Despite some controversy, the presence of a blood culture with Candida must require immediate treatment, at least to rule out an invasive power. Candida albicans remains the most frequent species, followed by Candida tropicalis, Candida parapsilosis and Candida glabrata, the latter usually associated with catheter infections. However, in recent years other species have emerged as C. krusei, C. lusitaniae, C. utilis, C. dublinensis and C. guillermondii. The introduction of fluconazole and other azoles has conditioned the selection of Candida albicans with azole resistance in these patients as C. krusei and C. glabrata, although other factors have been proposed 11 - 15.

Other fungi such as Trichosporon beigelii 16. 17, Blastoschizomices capitatus 18, Saccharomyces cerevisiae, 19 Rhodotorula spp and Malassezia furfur have been identified as causative agents of fungemia by yeasts agents, and vascular and peritoneal cauterization major risks to their development. Fusarium is a filamentous fungus that usually only cause fungemia, usually with necrotic skin lesions in patients with neutropenia harsh. Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides and Penicillium marneffei, the so - called regional fungi can also cause fungemia, but not specifically in neutropenic patients.

Pseudallescheria spp, Alternaria spp and Fusarium spp, which are hyaline filamentous fungi can cause infections indistinguishable from those produced by Aspergillus spp 20. 21. Mucormycosis usually produce rapid production and vascular necrosis, although this is extensible to all filamentous fungi. In addition to pulmonary involvement and abdominal rarest, is characteristic in neutropenic patients as in patients with diabetic ketoacidosis Rhinocerebral forms, with painful unilateral facial swelling, nasal discharge and Ophtalmoplegia serosanguinolenta 22. 23.
Management of febrile neutropenia The Infectious Diseases Society of America ( IDSA ) in its latest guidelines of 2002 contains a therapeutic classification of risk of infection in patients with neutropenia and patterns of action in relation to these risk groups 24. The theme is developed extensively in another chapter of this monograph, therefore only mention a few considerations.

In the past most of the recommendations emphasized the use of antibiotic combinations in this indication. However, in recent years there have been several studies that have shown the effectiveness of the guidelines on antibiotic monotherapy 25 - 27. A recent meta - analysis has ratified this trend ( Paul M et al ). This study collected 7800 patients in 47 randomized clinical trials conducted between 1981 and 2000. We compare patterns in monotherapy ( piperacillin / tazobactam, carbapenem, ceftacidima, cefepime ) in combination with patterns ( ureidopenicilina or third generation cephalosporin + aminoglycoside ). The overall mortality was 6. 2 %, no significant differences between the different patterns ( RR: 0. 85, CI95 %: 0, 72 - 1, 02 ). Nor were any differences in relation to the risk of colonization or superinfection 25.
Not recommended for initial use of vancomycin in these patients except one of the following circumstances: a ) clinical suspicion of catheter infection.

b ) known by Colonizacion S. pneumoniae resistant to penicillin or S. aureus resistant to methicillin.
c ) presence of severe mucositis.

d ) Patients who have received prophylaxis fluoquinolonas 28.
The use of antifungal drugs in these patients, the type and timing of use, have also been a source of constant debate. Recently the Spanish Society for Infectious Diseases ( SEIMC ), the Spanish Society of Hematology ( AEHH ) and the Spanish Society of Chemotherapy ( SEQ ), have developed a consensus that the recommendations for the use of antifungal drugs in these pacientes29. Maintain details of a late introduction after fever higher than 96 h, resistant to antibiotics. Its use is recommended for a correct clinical evaluation of the patient, including the completion of high - resolution CT, the determination ( optional ) galactomannan ( Aspergillus antigenemia ) in serum, the knowledge of antifungal prophylaxis used by the patient ( if any ) and the use of protected environments ( isolation room with HEPA filters for high efficiency ). If the patient has not received antifungal prophylaxis, and has remained in the room with HEPA filters can be used fluconazole, unless the CT and / or a positive galactomannan test indicating a possible aspergillosis. If the patient had received prophylaxis with azoles or has high risk of aspergillosis is recommended the use of amphotericin B or caspofungin. Amphotericin B deoxycholate remains its use in some centers. Among the lipid amphotericin group recommends the use of liposomal amphotericin ( 3 mg / kg / day ).

INFECTIONS ASSOCIATED WITH CELLULAR AND Humoral Immunosuppression Immune cells, unlike other types of patients and those infected by HIV, solid organ transplantation or suffering from graft versus host disease after allogeneic bone marrow transplantation, often do not have much relevance as neutropenia in cancer patients uncomplicated. However the use of high doses of steroids in some patients and particularly in recent years use of purine analogues such as fludarabine or cladribine, which produce a profound cellular immunosuppression, has changed this situation in recent years.
In addition to mycobacterium infections included in this section the infection by Listeria monocytogenes, Legionella spp, Nocardia spp, Salmonella spp. and other less common 30 - 32.

Two thirds of patients suffering from infection by Listeria spp affection of the central nervous system ( meningitis, encephalitis and meningoencephalitis ) and third party courses with primary bacteremia. Have also been described pneumonia, endophthalmitis, and myocarditis rectal abscesses.

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The gateway is gastrointestinal, and a debut of patients with diarrhea. In the case of meningoencephalitis, the cerebrospinal fluid usually shows pleocytosis with predominance of neutrophils, but not always, and hipoglucorraquia. Gram stain does not usually show the presence of microorganisms. The recommended treatment consists of aminoglycosides and ampicillin. Infection with Legionella spp. can be nosocomial or community. The clinical expression of acute pneumonia, associated with headache and abdominal pain. L. pneumophila is the most common, but infections have been described for other species, L. micdadei, L. bozemanii and L. dumoffii. These species have been associated with a greater tendency to cause pulmonary infiltrates with cavitation, although the most common presentation is patchy and prone to the extension. The visualization of the microorganism in respiratory samples by immunofluorescence or culture are the usual form of diagnosis, although in the case of L. pneumophila serotype 1, which is what justifies the 80 % of infections with this species, the detection of antigen in urine has a high profitability. Given the high mortality of the table, it is advisable to suspicion, the initiation of empiric treatment. Erythromycin, with or without rifampin, has traditionally been the treatment of choice. However the new macrolides, especially azithromycin, have superior in vitro activity and greater intracellular penetration and lung. The fluoquinolonas also possess an excellent activity 31, 32.

Although exceptionally well produced by Nocardia asteroides infections, and to a lesser extent by other species. Usually presents with nodular pulmonary infiltrates with a tendency to be accompanied by cavitation and pleural effusion. Very often the effect of the central nervous system, mostly in the form of abscesses. In the context of disseminated nocardiosis cutaneous manifestations are frequent, usually ulcerous type. Other rare locations include arthritis, myocarditis, adrenalitis, orchitis, and mediastinitis 32.
The frequency of infections by Salmonella non - typhi is clearly inferior to that seen in patients with HIV infection but can occur in cancer patients. Its most common form of presentation is the primary focus without bacteremia, but also describe urinary tract infections, gastroenteritis, soft tissue infection, arthritis, pneumonia, vascular infections, sinusitis, meningitis, peritonitis, and cholecystitis 32.

There have been reports of infections by microorganisms exceptionally rare. In this connection worth mentioning: Rhodococcus equi, Mycoplasma hominis, Ureaplasma urealyticum, Bartonella henselae, and 32 other Leuconostoc.
Cellular immunosuppression predisposes certain fungal infections such as cryptococcosis and pneumocystosis. Both are rare in patients not infected with HIV.

The predominant viral infections in cancer patients are caused by Herpes simplex, Herpes zoster and cytomegalovirus. Is very high frequency of herpetic stomatitis after mucositis in patients receiving chemotherapy, with the presence of painful ulcers in oral mucosa, including gums. It is not uncommon for the extension to the esophagus, simulating infection candidiasis. Perineal involvement alone is rare. The spread to the liver, spleen, lungs and kidneys can occur but is infrequent 32. 33.
The reactivation of Herpes zoster is common in these patients. Dermatomera usually affects a but with the possibility of multimetamerica or visceral involvement, including liver and brain. Varicella zoster pneumonia or other serious forms can be seen in children with acute lymphatic leukemia or lymphoma 34.

Virus infections are rare B or C is now given adequate control of blood products.
Cytomegalovirus infections are usually associated with reactivation or primary infection after intense immunosuppression or blood transplants. Although they can take with viral syndrome, are not rare gastrointestinal manifestations such as hepatitis or intestinal ulcers or esophageal 35. 36.

Are also prevalent in these patients respiratory virus infections such as respiratory syncytial virus, influenza, parainfluenza, adenovirus and picornavirus 37.
Cellular immunosuppression predisposes to infection by parasites and protozoa, but their incidence is extremely low in patients oncohematologic. However, it must take into account issues such as epidemiological history of prior illness or travel in these patients with unexplained fever. The reactivation of Toxoplasma gondii can cause brain abscesses. Have been described by Cryptosporidium enterocolitis. Strongiloides stercoralis can cause severe diarrhea and hiperinfestacion tables. In patients living in endemic areas is recommended Strongiloides stercoralis stool analysis to exclude asymptomatic carrier status before being subjected to immunosuppression 38.

INFECTIOUS COMPLICATIONS ASSOCIATED WITH THE USE OF LIKE slurry Purine analogues are routinely used in haematological malignancies of lymphoid origin, but are also used in the macroglobulinemia of Waldestrom, non - Hodgkin ' s lymphoma, Sezary syndrome and tricoleucemia.
Include: fludarabine, Cladribine, and pentostatina.

Produce different degrees of immunosuppression. A cellular level causing lymphopenia and inhibition of T cell cytokine; level granulocytic, Cladribine and fludarabine neutropenia occurring in 15 - 75 % and also enhanced the decrease in B cells, monocytes and immunoglobulins 39. 40.
The initial data with the use of purine analogues showed increased rate of infection by Listeria monocytogenes and P. carinii in early stages ( first 6 weeks ), and varicella zoster virus infections in later stages, with more profound lymphocytopenia. Have also been observed by Nocardia infections, tuberculosis and fungal infections.

All this has led to the use of prophylaxis in patients receiving purine analogues. This mainly includes the prevention of L. monocytogenes, Varicella zoster virus, P. carinii and fungal infections. In patients receiving fludarabine, some authors propose the use of cotrimoxazole, three times per week, up to 2 - 6 months after stopping treatment with fludarabine. Prevention antiherpatica is acyclovir ( 200 mg / 8h po ), or famciclovir ( 500 mg / 12 hours ) or valaciclovir ( 500 mg / 12 HRAS ) and its use is recommended in patients with prior herpetic infection or positive serology, whether there CD4 count <50 / mm 3, maintaining the same pattern in cases of recurrence.

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Another issue is the use of immunoglobulins and / or vaccination in seronegative cases. If carried out an autologous BMT and fludarabine is used in packaging recommends monitoring of cytomegalovirus antigenemia with PCR or with use of ganciclovir in case of replication and antifungal prophylaxis, similar to what was done in 41 allogeneic BMT, 42.

INFECTIOUS COMPLICATIONS ASSOCIATED WITH THE USE OF MONOCLONAL ANTIBODIES Table 3 lists the different monoclonal antibodies with therapeutic use in oncology and antigens to which they are designed.

Alemtuzumab ( Campath - 1H ) is an antibody directed against the cellular membrane glycoprotein CD52 expressed on most B lymphocytes and T normal and malignant NK cells, monocytes and macrophages. Produces myelosuppression, with neutropenia deep - fifth of patients. Produced by opportunistic infections lymphopenia ( CD4 and CD8 ), with slow recovery of counts ( up to 1 year ). A recent study ( Keating et al ) with alemtuzumab in patients with fludarabine failure to the presence of infection in 55 % of patients, being severe in 27 % of them. 10 % had sepsis ( gram - positive and gram - negative ) and 20 % developed infections during or after treatment ( Cytomegalovirus, Herpes Zoster, P. carinii, aspergillosis... ). Therefore, the authors recommend prophylaxis in patients receiving alemtuzumab with cotrimoxazole, fanciclovir fluconazole or itraconazole and severe neutropenia> 10 - 14 days, and monitoring of CMV during treatment or during the next 43 - 45 months.
Rituximab ( Rituxan ) is an antibody directed against the CD20 antigen present on B - lymphocytes CD20 is expressed in> 90 % of all B cell non - Hodgkin ' s lymphoma and chronic lymphoid leukemia. It is indicated in B - NHLs of low grade or follicular, in relapse or refractory B - NHL and in high or intermediate grade, alone or in combination with chemotherapy. Have been described associated with the following complications Rituximab: Reactivation of hepatitis B, reactivation of herpes virus and cytomegalovirus and parvovirus B19 to produce red cell aplasia 46 - 48.

MANAGEMENT OF INFECTIONS ASSOCIATED WITH CENTRAL VENOUS CATHETERIZATION Bacteremia associated with endovascular cauterization is the leading cause of bacteremia in these patients, especially gram - positive microorganisms.
Diagnosis of catheter - associated bacteremia In the presence of local inflammatory signs at the entrance of the catheter or blood cultures obtained by direct venipuncture, the diagnosis of certain infections associated with catheter through the removal of this and confirmation of the colonization of the distal segment of it. This is established when there are semi - quantitative culture by the presence of> 15 cfu after that segment bearing plate ( Maki technique ) or more than 1000 cfu / ml if there is a quantitative technique ( technique Cleries ). In the presence of bacteremia is possible to attribute the origin of the same catheter without removing it, through the use of paired quantitative blood cultures ( through a catheter and through direct venipuncture ). If you do not have quantitative blood culture, the qualitative interpretation of blood is always controversial because of the frequent contaminant of blood cultures of role players usually involved in catheter infection. Among the circumstances that support the catheter is the source of bacteraemia using qualitative blood cultures are repeated isolation of the organism ( at least 2 blood cultures positive for coagulase - negative ), growth in less than 24 - 48 h. from the extraction, the presence of inflammatory signs at the catheter insertion, and no other obvious source of bacteremia producer 49 - 51.

Importance of the causative agent The causative agent should be measured not only in the choice of specific antibiotics but when choose to retain the catheter. The experience gained in cases of infections caused by yeasts, S. aureus, Bacillus spp, Corynebacterium JK, and gram - negative bacilli ( mainly Pseudomonas spp and Stenotrophomonas spp ) is not favorable, with a high rate of relapses, much higher than those observed when the infections are caused by other agents, primarily by coagulase - negative. Therefore, in the presence of these agents is not recommended conservative treatment, catheter 51. 52.
How to deal without having to remove the catheter If there is suspicion of infection, we must always try and removal of the catheter. However, under certain circumstances, where the placement of a new catheter may be compromised because of patient characteristics and low virulent agents ( eg, clot - negative staphylococci ) may try conservative treatment. It is recommended that the antibiotic is administered through the catheter lights, even on a rotational basis, and ensure a sustained antibiotic exposure, prolonging the duration of administration. Evidence of this required prolonged exposure to antibiotics is the endoluminal techniques involving endoluminal sealing with antibiotics. This seal consists of the addition of antibiotics to the anticoagulant solution that is applied after use of the catheter until its next use. Makes even avoid the need for systemic administration of antibiotics beyond the extension of the table associated septicemia, although controlled studies are expected to recommend the use of sealing as a treatment additive and not a substitute for systemic antibiotics. Recommended doses range from 0. 1 mg / ml and 5 mg / ml. Have been successfully used in sealing various antimicrobials, including vancomycin, teicoplanin, clindamycin, rifampin, aminoglycosides or quinolones. It should be noted that conservative treatment should always carry an implicit special clinical surveillance of the patient, especially in the first 48 - 72 hours. If after this time the patient continued with fever or signs suggestive of infection should withdraw the catheter 53. 54.

Men Yeast Infection Treatment Tips 1. Don't wear pads or panty-liners beyond the length of your period. 2. Don't use deodorant tampons. 3. Avoid feminine deodorant sprays and douches. 4. Wipe from front to back after urination and bowel movement. 5. Antibiotics can also cause a yeast infection, since they kill or decrease normal flora. 6. Avoid tight-fitting clothing and wear cotton, rather than synthetic, underwear. 7. Avoid wearing wet clothing for long periods of time. 8. Avoid tight fitting clothing. 9. Avoid diets rich in sugar. Sugar can alter the pH balance. 10. Dry the area thoroughly after you shower or bathe 11. Get plenty of rest to help the body fight infections 12. Wear all-cotton underpants and panty hose with cotton crotches