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By F. Hogar. University of Puget Sound.

Subdural blood can travel along the inside of the skull with a typically concave inner margin metoclopramide 10mg discount, stopping only at dural reflections cheap 10 mg metoclopramide with mastercard, such as the falx cerebri and the tentorium cerebelli buy metoclopramide 10mg with amex. Extradural haematoma has a typically biconvex, lentiform configuration and cannot pass beyond sutural lines. She is a life-long smoker with moderate alcohol intake and suffers from diabetes, which is diet controlled. Examination the patient is haemodynamically stable and afebrile; cardiovascular and abdominal examinations are unremarkable. Respiratory examination reveals finger clubbing, reduced air entry bilaterally with no added sounds and dullness to percussion at the right apex. Neurological examination reveals reduced power of the muscles in the right upper limb at 3/5, with reduced sensation to light touch; tone and reflexes are normal. The chest x-ray shows an opacity at the right lung apex (arrows C) seen on a magnified view of the right apex included in ure 45. Here the associated destruction of the posterior right upper second rib can be clearly seen (arrows A). Horner syndrome, due to disruption of the sympathetic plexus as it dips down below the thoracic inlet – this comprises ptosis, miosis and anhydrosis on the affected side. There are other causes of Horner syndrome where the sympa- thetic plexus is involved in the neck or at the skull base (e. Unfortunately, by their nature these tumours are usually inoperable by the time they present due to chest wall/mediastinal invasion. The nursing staff have passed a nasogastric tube which was technically difficult and would like to start feeding the patient. However, it is reasonable (and fair on the patient) that this is reattempted the next morning (unless feeding is urgent, this is unusual). Nasogastric tube insertions are generally performed on the ward by nursing staff, but junior doctors may be called in difficult cases or where a chest x-ray has been performed following tube insertion to confirm position. Unfortunately, nasogastric tube insertion is associated with morbidity and mortality usually due to malposi- tioning in a bronchus and written guidance on insertion should always be available. Generally, if the nurses have struggled to insert a tube or if the litmus test for stomach contents is negative on aspiration of the tube, then a chest x-ray will be requested to confirm tube position. Ideally, tube insertion should be done during the day when senior medical and nursing staff are available (also radiologists in the department). If you are unsure about an x-ray appearance and are put on the spot late at night, it may be best to advise a delay in any feeding until the morning when senior help is readily available, or seek senior help at the time. Always document all discussions and decisions in the patient record and sign/date/time all entries, document any discussions with col- leagues also. Mistakes have occurred in patients who have had multiple x-rays with the nasogastric tube position assessed on a previous film and incorrect advice then given. She reports having not felt well for the past few months, with progressive tiredness and shortness of breath when walking up the hill to her local shops. She has a past medical history including stable angina, asthma, a previous laparoscopic cholecystectomy for cholecystitis and a right hip replacement for arthritis. She has no known allergies, and apart from the laxatives, takes anti-hypertensives, aspirin and salbutamol (as needed). She currently lives alone in a ground-floor flat with no carers, and is independent in activities of daily living. Examination Examination of the cardiorespiratory system revealed occasional scattered expiratory wheezes and hyper-expanded lungs. Her abdomen was distended and tender to palpa- tion, but soft, with no palpable masses or hepatosplenomegaly. This lady has an acute large bowel obstruction, most likely secondary to a primary colonic malignancy. The large bowel is dilated into the left pelvis suggesting a low obstructing lesion, note absence of gas in the rectum. The tumour will have been slowly increasing in size, causing her progressive problems with constipa- tion, until the tumour size caused complete bowel obstruction: the cause of her acute presentation. Her microcytic anaemia would suggest that she is suffering from iron deficiency anaemia, which often occurs secondary to a lower gastrointestinal malignancy. Blood loss can be chronic and at a rate too slow for overt black stools (melaena) to be noted by the patient. Assessment of the patient’s iron status with a serum ferritin will confirm the iron deficiency, but care must be taken as ferritin can be falsely elevated in acute infection or inflammation. Acute management of this patient will be surgical, and will involve nasogastric decompression of the proximal bowel, along with intravenous fluid resuscitation, while plans for surgical intervention are made. She also has stable angina which indicates an element of ischaemic heart disease and possible heart failure. It is therefore possible that she has distant metastases, including lung metastases, which may account for her breathlessness. Another point to note is that malignancy is a strong provoker of throm- bosis through a number of mechanisms, both with direct effects, such as compression by the tumour of the iliac vessels within the abdomen and pelvis, and also from throm- bogenic factors released from tumour cells. Microcytic anaemia the main acquired causes of microcytic anaemia are iron deficiency and acquired sideroblastic anaemia. Case 47: Elderly woman with constipation 233 They include thalassaemia, sickle cell disease, congenital sideroblastic anaemia, and hereditary spherocytosis. Key points • A change in bowel habit with microcytic anaemia, particularly from the fifth decade onwards, strongly suggests bowel pathology, and further investigation is warranted. In this case, the symptoms and anaemia were left until the tumour was so large that bowel obstruction occurred, indicating advanced-stage malig- nancy. She suffers from hypothyroidism and is on replacement therapy, and wonders if she needs to increase her dose of thyroxine. She denies any recent coughs or colds, fevers, weight loss or change in bowel habit, and apart from fatigue, has no other symptoms. Apart from her thyroxine, she is on no other medication, and has an allergy to penicillin after developing a rash with previous use. The fatigue is now severe enough to interfere with her coursework and she has been finding it hard to concentrate on lectures. Examination Cardiovascular, respiratory and abdominal examination was normal with no cardiac murmurs present, and a regular pulse rate of 82 beats per minute. Examination of the oropharynx revealed a normal-sized, slightly erythematous tongue, but no ulcers were noted. There are a number of possible causes of macrocytic anaemia, which include hae- matinic deficiencies of folate and vitamin B12, as well as liver disease, alcohol excess, untreated hypothyroidism, myelodysplastic syndromes and a number of pre- scription medications. Investigations would look to exclude these differentials, with B12/folate, thyroid functions tests, liver function tests and a blood film to confirm macrocytosis and exclude myelodysplastic syndrome.

However cheap metoclopramide 10 mg mastercard, a recent order 10mg metoclopramide with visa, large randomized trial in cardiac surgery patients showed no renal protective effect [16] cheap metoclopramide uk. Coexisting fever or any other evidence of urinary infection proximal to the obstruction requires a rapid decompression procedure to avoid bacteremic shock. If this is not possible, as is occasionally the case in patients with prostatic enlargement or urethral stricture, urethral dilation or percutaneous cystostomy should be performed. Because of the defects in distal nephron function associated with high- grade obstruction, patients may develop hyperkalemia, hyperchloremic metabolic acidosis, and hypernatremia. Water and bicarbonate replacement are often required and can be administered as a solution of 5% glucose and water to which sodium bicarbonate has been added. Hyperkalemia may respond to the institution of a diuresis that accompanies the relief of the obstruction and as well as correction of the acidosis. As such, this postobstructive diuresis is considered appropriate to the pre-existing volume expansion. In some patients with correction of bilateral obstruction, a large diuresis and natriuresis may ensue, which result in hypovolemia and, sometimes, frank shock. The mechanism for this inappropriate diuresis is poorly understood but may involve release of a natriuretic substance. These patients require fluid replacement, usually with hypotonic saline, to repair the deficit and match urinary losses. A useful technique is to measure the urinary sodium and potassium concentrations periodically to determine the composition of the replacement fluid. However, care must be taken to avoid excessive fluid replacement as this will simply prolong the diuresis. When possible, aminoglycoside antibiotics or other nephrotoxic drugs should be replaced with nonnephrotoxic agents. If this is not feasible, the risk should be minimized by taking prophylactic measures (see previous discussion). In addition, the dosage of drugs dependent on renal metabolism and excretion should be adjusted appropriately. If the dose or dosing interval is unchanged, reduced renal function leads to accumulation of the drug in body fluids and eventual drug toxicity. Phenytoin, independent of its excretion, may reach toxic concentrations because a larger proportion of the administered drug is displaced from albumin-binding sites in uremia. Drug doses need to be altered in most instances to account for residual renal function and the effect of dialysis on drug removal. It is important to remember that as the patient recovers renal function, upward adjustment of the dosage of renally excreted drugs is necessary. The degree of catabolism reflects the level of the patient’s metabolic stress and is, in turn, a function of the severity of the underlying illness. Protein and caloric requirements are much higher for patients with catastrophic illness and multiple organ system failure than for those with mild or moderate illness. Although caloric replacement needs to be adequate to reduce tissue catabolism, prevent ketosis, and meet the patient’s basal nutritional needs, the clinician must avoid providing excessive substrate for generation of metabolic waste products. This is particularly challenging for patients who are not yet being dialyzed; once patients are on dialysis, they are allowed more liberal fluid intake and can receive a greater intake of carbohydrates, protein, and fat, limited only by the rate of dialytic fluid and solute removal. As discussed in Chapters 212 and 214, the need for nutritional support is becoming an indication for renal replacement therapy [91]. Hyperkalemia Hyperkalemia is the most immediately life-threatening electrolyte imbalance encountered in patients with renal disease (see Chapter 199). Urine flow rate is an important determinant of tubular potassium secretion; therefore, oliguric patients are more prone to potassium imbalance than are nonoliguric patients. Metabolic Acidosis the kidneys’ ability to excrete metabolically produced acids may be reduced, particularly in parenchymal and obstructive disease. Indeed, pure tubular acid excretion abnormalities may exist independently of azotemia (renal tubular acidosis). Metabolic acidosis that results from failure of the tubules to excrete hydrogen ions or conserve bicarbonate normally produces a hyperchloremic or low anion gap acidosis (see Chapter 198). Bicarbonate supplementation in the setting of metabolic acidosis remains controversial as there are no studies demonstrating a beneficial effect of this approach. In addition, bicarbonate supplementation may cause volume overload and hypernatremia and may exacerbate hypocalcemia by lowering the ionized calcium level. Abnormal Salt and Water Metabolism Although most fluids administered to patients are hypotonic, plasma osmolality normally remains within tightly fixed limits. The process by which plasma tonicity is preserved depends on the suppression of vasopressin release and the movement of free water in the ascending limb of the loop of Henle. This situation, referred to as nephrogenic diabetes insipidus, is most common in tubulointerstitial disease and in partial obstruction of the urinary tract. High serum phosphorus levels lead to formation of insoluble calcium phosphate salts, which may precipitate in soft tissue. If the product of the serum calcium and phosphorus concentrations exceeds 70, precipitation in soft tissues becomes more likely. Although there is no published data correlating the treatment of hyperphosphatemia with improved outcomes, phosphate binders are typically initiated when phosphate levels rise to more than 6. The main phosphate binders available include calcium salts (calcium acetate and calcium carbonate), sevelamer, and lanthanum hydroxide. Although potent, aluminum- based binders are generally avoided because of concerns with aluminum toxicity. The exact identities of the so-called uremic toxins are not known, although many possibilities have been suggested. One cannot deduce on the basis of urea nitrogen and creatinine levels exactly when a patient will become uremic. Other, less subjective uremic manifestations constitute stronger indications for prompt initiation of dialysis, including bleeding diathesis, seizures, coma, and the appearance of a pericardial friction rub. Patients with intractable volume overload, hyperkalemia, metabolic acidosis, or frank uremia clearly meet criteria for dialysis. Nevertheless, several observational studies appear to show decreased morbidity and mortality for patients initiated on early dialysis. It has been argued that early dialysis results in improved volume control as well as the clearance of a variety of cytokines and/or toxins that may be harmful. Unfortunately, at this time, there is still not adequate data to establish the optimal time to initiate dialysis. Most of these individuals do not have multiorgan failure, and their improved survival may be the result of a less severe primary illness. Patients with prolonged episodes of ischemia or injury may have variable degrees of recovery [100–102]. Alternatively, a phased array cardiac probe gives serviceable images when configured with abdominal presets. Scanning Technique With the patient in the supine position, the probe is placed in the posterior axillary line over the lower lateral chest wall in order to obtain a transcostal coronal plane view of the left right or left kidney in their longitudinal axis (Video 200. Useful landmarks for locating the kidneys are the liver or spleen, as the kidneys are adjacent and caudal to these organs.

A positive family history of early onset of ioural disorders order metoclopramide 10 mg otc, diabetes and increased early mortality [6] cheap 10mg metoclopramide with visa. Brain imaging is important safe 10 mg metoclopramide, and therefore treatment will result in adult height that is especially in girls with an onset of puberty before the age significantly greater than would be expected than if the of 6, where 20% will be found to have a central nervous child were left untreated. It is appropriate in these young children to sup- This is far less common than central precocious puberty press the development of secondary sexual characteristics. The standard treatment for central precocious puberty is Causes include the following. If a large ovarian cyst is present, this may be administered until such time as the child reaches approximately age 11, when withdrawal will result in the be part of McCune–Albright syndrome, with associ- normal resumption of pubertal changes. Peripheral pre- ated classical features of irregular café‐au‐lait spots and cocious puberty, when due to an ovarian or adrenal cystic bone lesions called polyostotic fibroid dysplasia. Investigations Delayed puberty A number of hormonal studies may be carried out in chil- dren with precocious puberty. However, they are of limited Delayed puberty is usually considered when girls have no value and should be focused on specific clinical entities. Estradiol is usually elevated in girls with precocious aetiology for this may be extremely important. There are often extremely Treatment good reasons why a mother will bring her daughter for investigation and this often relates to the fact that a sib- the majority of girls with central precocious puberty do ling completed her pubertal development at an earlier age not require hormonal treatment, because most develop- or she herself went through puberty at an earlier age. It is therefore prudent to review children with pre- cocious development of secondary sexual characteristics 6 months later to see whether there has been rapid develop- Summary box 38. In these Precocious puberty is usually idiopathic and requires cases, there is a high chance that sexual maturity will be treatment only if changes are accelerated such that com- reached by age 9 and therefore suppression of the progress pletion of puberty will occur prematurely. While it is possible to sup- 546 Childhood and Adolescence Aetiology of primary amenorrhoea Table 38. Secondary sexual characteristics normal From a clinical point of view it is probably best to classify Imperforate hymen the aetiologies of primary amenorrhoea based on the Transverse vaginal septum presence or absence of secondary sexual characteristics. Finally, there is the group of patients in whom Resistant ovary syndrome there is heterosexual development. It may present in early childhood when the Olfacto‐genital syndrome infant presents with a bulging hymen behind which is a Acquired Weight loss/anorexia mucocele, the vagina expanded by vaginal secretions of Excessive exercise mucus. This is easily released and does not subsequently Hyperprolactinaemia cause any problems following hymenectomy. The Gonadal dysgenesis vagina is a very distensible organ and can allow quite Turner mosaic large quantities of blood to collect in some cases. When some Short stature blood does accumulate within the cavity it is known as Hypogonadotrophic hypogonadism haematometra. As the vaginal mass enlarges there may Congenital: hydrocephalus be associated difficulty with micturition and defecation. Acquired Examination will occasionally reveal an abdominal Trauma swelling and observation of the introitus will display Empty sella syndrome Tumours a tense bulging bluish membrane, which is the hymen Hypergonadotrophic hypogonadism (see Chapter 35). If the space between the upper and lower vagina is considerable, no introital swelling may be visible Absent vagina and a functioning uterus and rectal examination may disclose a mass. The manage- This is a rare phenomenon when embryologically the ment is very different from imperforate hymen and very uterine body has developed normally but there is fail- careful assessment must be made before embarking on ure of development of the cervix. The presenting Puberty and Its Disorders 547 symptom is again cyclical abdominal pain, but there is Constitutional delay no pelvic mass to be found because there is no vagina to A number of girls have constitutional delay and normal be distended. Although a small haematometra may be secondary sexual characteristics, but there is no anatom- present, retrograde menstruation occurs leading to the ical anomaly and endocrine investigations are all normal. This is the sole reason for their con- Absent vagina and a non‐functioning uterus stitutional delay. These young women will eventually This is the second most common cause of primary amen- menstruate spontaneously as the maturation process orrhoea, second only to Turner’s syndrome. Often small uter- ine remnants (anlage) are found on the lateral pelvic side walls. This condition arises due to maldevel- ure of the testis to produce androgen (particularly testos- opment of neurones in the arcuate nucleus of the hypo- terone), and androgenic receptor absence or failure of thalamus. In androgen insensitivity there is a structural from the olfactory bulb and therefore some patients may abnormality of the androgen receptor, due to defects in also have failure of development of the ability to smell the androgen receptor gene, which results in a non‐func- (anosmia). The genetic basis of these two syndromes of testosterone during normal development is prevented remains to be clarified. Currently, 24 gene mutations have and patients are therefore phenotypically female with been described but these only explain 60% of cases [9]. This occurs because of peripheral conversion of androgen to oestrogen and sub- Weight loss/anorexia sequent stimulation of breast growth. Pubic hair is very Weight loss is more commonly associated with second- scanty in these patients as there is no androgen response ary amenorrhoea than primary amenorrhoea, but unfor- in target tissues. The vulva is normal and the vagina is tunately it is increasingly apparent that younger girls usually short. This leads to failure of initiation of puberty and Resistant ovary syndrome therefore a persistent hypogonadotrophic state exists. This is an extremely rare cause of primary amenorrhoea, the growth spurt is not usually influenced by this, but but it has been described. It is essential to obtain an the gonad is described as dysgenetic if it is abnormal in assessment of body fat, which is much more discrimina- its formation. Examples include ballet dancers, athletes and gym- tions that vary with the degree of differentiation. The nasts and some of these girls may actually develop commonest is Turner’s syndrome, where there is a single associated anorexia nervosa. There may be a recognizable prolacti- Other structural chromosomal anomalies associated with noma in the pituitary, but often no apparent reason is gonadal dysgenesis involve deletions. In Turner’s syndrome ovarian development Gonadal agenesis is normal until 20 weeks’ gestation and at this stage In this condition there is complete failure of develop- oocytes are found in the ovaries. The ovaries in most individuals recessive disorder and genes other than those located on consist solely of stroma and as there are no oocytes the X chromosome may be involved. There genes remains unclear and in all these patients their is a normal female phenotype and internal genital devel- genotype does not affect their phenotype, all of them opment is also normal. In mosaicism the pro- as the cause of the failure of differentiation of the portion of each cell line determines the manifestation of gonad, there is absence of testicular development. The higher the percentage of 45X cells, the individuals therefore fail to produce any androgen or more likely the features of Turner’s syndrome. This is usually associated with external genitalia reflect the normal female phenotype. The that their long bones do not undergo epiphyseal closure external phenotype is therefore female with a short vagina. Absent secondary sexual characteristics Ovarian failure (short stature) These unfortunate girls have ovarian failure as a result of Congenital infection either chemotherapy or radiotherapy for childhood the most common aetiology in this group is hydroceph- malignancy.

The serial purchase metoclopramide 10 mg mastercard, empiric addition of one antibiotic after another without culture data is not efficacious in most settings and may lead to confusion in the event that an adverse reaction occurs [52] order line metoclopramide. Cephalosporins and vancomycin can cause bone marrow suppression and lead to colonization with resistant organisms order generic metoclopramide. The addition or sequential substitution of multiple cephalosporins may induce β-lactamase production by some organisms. Persistent or Recurrent Fever Without Obvious Source: Neutropenia Should fevers persist for 4 to 7 days of neutropenia, randomized controlled trials have found that empiric antifungal therapy with an amphotericin B preparation, voriconazole, or an echinocandin [60–62] is appropriate. The rationale for such therapy is that it is difficult to culture fungi before they cause disseminated disease and that the mortality from disseminated fungal disease among neutropenic hosts is high. Candida and Aspergillus species are common pathogens, and Fusarium, Trichosporon, and Bipolaris species are seen occasionally but are becoming more common [63–66]. The use of the serum assay for galactomannan as a marker for aspergillus infection is controversial because sensitivity is low and there may be false-positive results in patients receiving piperacillin [67,68]. Another serum assay that tests for 1,3 β-D-glucan antigenemia shows promise, but serial monitoring is needed and predictive value for invasive fungal infections varies in different centers [69,70]. Patients at particularly high risk of disseminated fungal disease include those with (a) prolonged granulocytopenia, (b) parenteral nutrition, (c) Candida colonization in oropharynx or urine, (d) corticosteroid therapy, and (e) advancing multiple organ dysfunction (renal, hepatic, pulmonary). The use of antifungal prophylaxis with the imidazoles (fluconazole) has caused a shift in the species of Candida- causing infection from C. Hepatosplenic (also called chronic disseminated) candidiasis presents with fevers and elevation of serum alkaline phosphatase that continue through the return of 3 neutrophils to greater than 1,000 cells per mm [75]. Multiple embolic lesions are present in liver and spleen, and prolonged therapy with amphotericin B, itraconazole, fluconazole, or an echinocandin depending on the susceptibility of the organism, is beneficial [76]. Based on the findings from a randomized clinical trial of primary therapy and randomized studies of salvage therapy, voriconazole is the drug of choice for infections caused by Aspergillus [79,80]. However, an amphotericin preparation continues to be the drug of choice when a fungal infection is suspected in patients already receiving an azole antifungal [74]. According to data from randomized clinical trials, the newer preparations of amphotericin B appear to decrease renal toxicity while maintaining efficacy: therefore, amphotericin B complexed with cholesteryl sulfate, with liposomal vesicles, or with a bilayered lipid membrane has become standard for use in patients on other nephrotoxic drugs or those with impaired renal function, despite their higher cost [81] (see Chapter 73). Prognosis remains poor, however, for patients treated for documented invasive fungal infection in the setting of persistent neutropenia [63,82]. Pulmonary disease can be caused by a wide variety of agents, including bacteria, protozoa, helminths, viruses, fungi, and mycobacteria (Table 75. The differential diagnosis is made even more difficult by the various noninfectious pulmonary complications that can present abruptly with acute respiratory symptoms and fever. These include underlying malignancy or vasculitis, drug toxicity, interstitial fibrosis, diffuse alveolar hemorrhage, radiation pneumonitis, cardiogenic pulmonary edema, bronchiolitis obliterans organizing pneumonia, pulmonary alveolar proteinosis, and pulmonary embolism [48,87]. Regardless of cause, fever and progressive shortness of breath (and concomitant tachypnea and arterial hypoxemia) tend to be common symptoms; in the neutropenic patient, cough, sputum production, and physical examination (as well as radiographic) findings are likely to be unimpressive or absent. Differential Diagnosis Developing an appropriate differential diagnosis for the causative agents of pneumonia in the immunocompromised host rests first on an appreciation of the nature, severity, and duration of the immune suppression. Patients who have resided in tropical countries may reactivate latent infection by Strongyloides stercoralis in the setting of altered cell-mediated immunity. Pulmonary infiltrates, polymicrobial bacteremia, and bacterial meningitis are the hallmarks of this syndrome [98]. Chest radiographs may provide useful clues; focal or multifocal infiltrates tend to suggest infections by bacteria or fungi, but are unlikely to provide a definitive diagnosis. Cavities also can be a late finding with pneumonia because of Aspergillus, Zygomycetes, and Nocardia spp. Gram-negative bacilli or Legionella may progress to diffuse disease or incite the acute respiratory distress syndrome. Patients with severe defects in cell-mediated immunity may manifest a miliary pattern caused by disseminated tuberculosis or histoplasmosis. Conversely, radiation pneumonitis may present as focal, sharply demarcated infiltrates confined to the irradiated portion of the lung. Diagnostic Approach and Empiric Therapy the diagnostic approach to pulmonary disease in the immunocompromised host also depends on the nature of the immune deficit. As a general rule, all accessible sites (blood, urine, and sputum) should be cultured, although sputum of high quality is obtained rarely in these circumstances. In neutropenic hosts, empiric antibacterial therapy is begun at the outset regardless of radiographic pattern, using one of the regimens discussed previously for fever and neutropenia [37,38]. These regimens typically contain more than one antibiotic and they should be adjusted based on the cumulative susceptibility report of the hospital or unit. Although logical, the use of “protected specimen brushes” has not been shown to be of clear clinical value and should not be a reason to perform an invasive procedure in an immunocompromised patient [99]. In the setting of persistent neutropenia, a clinical picture of progressive pulmonary disease despite antibiotic therapy suggests invasive disease caused by fungi found in the environment (a variety of “saprophytic” fungi are a major concern: especially Aspergillus, but also Rhizopus, Fusarium, and Trichosporon spp) [39,65,66]. Expectorated sputum, bronchial brush specimen cultures, or bronchial lavage fluid may provide presumptive evidence of these pathogens, but prompt definitive diagnosis often requires open or thoracoscopically guided lung biopsy. Typically, pneumonia caused by Aspergillus or Zygomycetes spp causes areas of lung infarction that may be missed by transbronchial biopsy [100,101]. Unlike bacteria, which are usually easy to culture, fungi are often not isolated from cases where histopathology eventually demonstrates their presence. The standard approach to therapy of confirmed pulmonary disease caused by Aspergillus is to treat with voriconazole because this agent has been shown to be superior to treatment with amphotericin B preparations [80,102]. Although the use of combinations of antifungal agents (including echinocandins and azoles as well as echinocandins and amphotericin) has rationale, support from animal data, and anecdotal human experience, large trials have yet to be performed, making it difficult to recommend this approach at this time unless single agents have failed. There is no established therapy for some emerging fungal pathogens such as Trichosporon or Fusarium spp, although encouraging results have been reported in a few cases using posaconazole, voriconazole, or isavuconazole [102,103]. For patients with compromised T-cell immunity, the list of diagnostic possibilities is longer and more diverse, making a single formula for empiric therapy a virtual impossibility. Clinicians caring for these patients should be guided by both the type of the underlying immunodeficiency and the patient’s previous experiences with both pathogens and antimicrobial agents. Expectorated or induced sputum may demonstrate the organism by special stains in a minority of cases (P. Bronchoscopy is particularly helpful for diffuse or interstitial disease, in which it provides not only lavage fluid with reasonable diagnostic accuracy for infectious agents such as P. In patients with focal or nodular disease, thoracoscopically assisted biopsy is likely to yield the best results. It is usually an error to postpone performing bronchoscopy (with biopsy) or thoracoscopically guided lung biopsy for severely ill immunocompromised patients with pulmonary infiltrates in the hope that they will improve, because clinical deterioration may make the procedure (and the diagnosis) impossible. Early efforts were directed at modifications of the environment of neutropenic patients through laminar airflow, nonabsorbable antibiotics, and elaborate efforts at disinfecting the inanimate environment. These approaches have proven expensive and laborious, and because they did not affect either disease remission or mortality, they have been abandoned by most centers. These agents reduce levels of aerobic Gram-negative bacilli in the gut lumen, the major reservoir for dissemination of infection in the neutropenic host, and studies document the efficacy of levofloxacin for preventing infections and hospitalizations in patients with chemotherapy-induced neutropenia [109]. Recent studies suggest that posaconazole, which has a much broader spectrum than fluconazole (including aspergillus), is efficacious in preventing fungal infections in severely neutropenic patients, hematopoietic stem cell transplant patients, and those with graft versus host disease [110]. Administration of granulocyte–colony stimulating factors hastens bone marrow recovery and shortens the duration of neutropenia in some patients receiving chemotherapy. Consensus guidelines suggest that they should be used to support dose-intense chemotherapy and have little impact on mortality in patients with existing neutropenia and fever and should not be used as a routine adjunct to antimicrobials [113].

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