Sandbox:Prince

ANTIFUNGAL THERAPY IN FUNGAL MENINGITIS
Type of fungal meningitis	Preferred therapy	Alternate therapy
Aspergillus	Voriconazole 6 mg/kg IV q12h on day 1 followed by 4 mg/kg q12h; further conversion to oral therapy may be considered. Typical oral dosing is 200 mg q12h but is dependent on therapeutic drug monitoring. Total duration of therapy has not been defined. Multiple factors must be considered, including extent of disease, response to therapy, and underlying immune status of the host.	Liposomal AmB 3-5 mg/kg/day IV, ABLC 5 mg/kg/day IV, itraconazole 200 mg PO BID, or posaconazole 200 mg PO q6h. Note that combination therapy with voriconazole and an echinocandin such as caspofungin 70 mg IV on day 1 and 50 mg/day IV thereafter may be considered.
Candida	LFAmB 3-5 mg/kg/day +/− flucytosine 25 mg/kg QID for ∼3 weeks followed by fluconazole 400-800 mg/day PO/IV (6-12 mg/kg/day) Treatment continued until clinical signs and symptoms resolved and CNS and radiographic abnormalities have normalized.	Fluconazole 400-800 mg/day PO/IV (6-12 mg/kg/day)
Blastomyces	LFAmB 5 mg/kg/day for 4-6 weeks followed by fluconazole 800 mg/day PO/IV Treatment for at least 12 months and until resolution of CSF abnormalities	Alternative azole considerations include itraconazole 200 mg PO BID to TID and voriconazole 200-400 mg PO BID.
Coccidioides	Fluconazole 400 mg/day PO/IV. Some use higher doses of fluconazole, up to 1,000 mg/day up-front. Azole therapy is typically continued indefinitely.	Itraconazole 200 mg PO BID to TID The addition of intrathecal AmBd to azole therapy may be considered in those not responding to azoles. Intrathecal AmBd dosing ranges from 0.1 to 1.5 mg per dose given daily to weekly.
Cryptococcus	HIV-infection (Induction/consolidation): AmBd 0.7-1.0 mg/kg/day IV plus flucytosine 25 mg/kg PO QID for at least 2 weeks followed by fluconazole 400 mg/day PO/IV (6 mg/kg/day); LFAmB may be substituted for AmBd if necessary: liposomal AmB 3-4 mg/kg/day IV and ABLC 5 mg/kg/day IV. (Maintenance): Fluconazole 200 mg/day[null b] Solid organ transplant: LFAmB (liposomal AmB 3-4 mg/kg/day IV or ABLC 5 mg/kg/day IV) plus flucytosine 25 mg/kg PO QID for at least 2 weeks followed by fluconazole 400-800 mg/day PO/IV (6-12 mg/kg/day) for 8 weeks followed by fluconazole 200-400 mg/day for 6-12 months Non-HIV, non-organ transplant: AmBd 0.7-1.0 mg/kg/day IV plus flucytosine 25 mg/kg QID for at least 4 weeks followed by fluconazole 200 mg/day (3 mg/kg) for 6-12 months	HIV-infection (Induction/consolidation): AmBd 0.7-1.0 mg/kg/day IV or LFAmB (liposomal AmB 3-4 mg/kg/day IV and ABLC 5 mg/kg/day IV) monotherapy for 4-6 weeks; AmBd 0.7 mg/kg/day IV plus fluconazole 800 mg/day PO/IV for 2 weeks followed by fluconazole 800 mg/day for a minimum of 8 weeks; fluconazole (≥800 mg/day) PO/IV plus flucytosine 25 mg/kg PO QID for 6 weeks (Maintenance): Itraconazole 200 mg PO BID[null b] Solid organ transplant: If flucytosine not used, then consider extension of induction with LFAmB for at least 4-6 weeks. Non-HIV, non-organ transplant: LFAmB (liposomal AmB 3-4 mg/kg/day IV or ABLC 5 mg/kg/day IV) can be substituted in those unable to tolerate AmBd; if flucytosine not used, then consider extension of AmBd or LFAmB induction for at least 2 additional weeks.
Exserohilum	Voriconazole 6 mg/kg IV every 12h with assessment of voriconazole trough concentrations on day 5 of therapy with adjustment to achieve trough of 2-5 mcg/ml. IV therapy should be initiated in most cases with transition to PO therapy once improving and clinically stable. Total duration of therapy is unknown and will depend on extent of infection, response to therapy, and underlying immune status of the host. Minimum duration of 3-6 months.	The addition of liposomal AmB 5-6 mg/kg/day IV should be considered in patients with severe disease and/or not responding appropriately to voriconazole monotherapy. Doses of liposomal AmB up to 7.5 mg/kg/day IV may be considered in patients who continue to do poorly.
Histoplasma	Liposomal AmB 5 mg/kg/day IV for 4-6 weeks followed by itraconazole 200 mg BID to TID for at least 1 year and until resolution of CSF abnormalities including Histoplasma antigen levels.	AmBd 0.7-1.0 mg/kg/day is an alternative to liposomal AmB in patients at low risk of nephrotoxicity.
	IV, intravenous; AmB, amphotericin B; ABLC, amphotericin B lipid complex; PO, per os, oral administration; BID, twice daily; LFAmB, lipid formulations of amphotericin B; TID, three times daily; QID, four times daily; AmBd, amphotericin B deoxycholate.

According to severity of the disease
Mild	Early diagnosis and treatment Responds to medical treatment Typical clinical presentation Good prognosis
Moderate	May present late with typical or atypical symptoms May present with complications Variable response to treatment
Severe	Presents with complications or prolonged illness Immunocompromised Common in extremes of age Delayed diagnosis and treatment Surgical treatment may be required in addition to medical treatment Increased morbidity and mortality
According to the duration of disease
Acute	Lasts few weeks Patient acutely ill Mostly in HIV-associated patients Impaired consciousness Seeks medical treatment early due to sudden deterioration
Subacute	Lasts less than 4 weeks Patient acutely ill Mostly in HIV-associated patients Impaired consciousness Seeks medical treatment early due to sudden deterioration
Chronic	Lasts more than 4 weeks Gradual deterioration of patient Prolonged history of atypical symptoms Common in older patients
Recurrent	Multiple episodes which lasts less than 4 weeks History of incompliance to medication immunosuppression may be the underlying cause

Variable	Empyema Thoracis	Lung abscess	Pleural effusion	Pneumonia	Lung cancer
Presentation	Variable presentation but may follow long standing pneumonia	Usually has history of aspiration pneumonia, alcoholics, drug abusers, seizure disorder, have undergone recent general anesthesia, or have a nasogastric or endotracheal tube.	Usually follows pneumonia as a complication	presents with fever, pleuritc chest pain, cough	mostly asymptomatic but may have cough productive with hemoptysis and chronic history of smoking
Causes	In general any bacteria can cause an empyema, however different bacteria are associated with different rates of empyema formation.[1]  Common causes include bacteroides, fusobacterium,  haemophilus influenzae, pneumococcal infections, staphylococcus aureus, streptococcus, TB	Lung abscess is commonly caused by bacterial infections and these include bacteroides, peptostreptococcus and prevotella mostly after aspiration	Common causes of transudative pleural effusion include;[1][2][3][4][5] left ventricular failure, Nephrotic syndrome, and cirrhosis, while common causes of exudative pleural effusions[6] are bacterial pneumonia and malignancy	Pneumonia can result from a variety of causes, including infection with bacteria, viruses, fungi, parasites, and chemical injury to the lungs	Direct cause of lung cancers is DNA mutations that often result in either activation of proto-oncogenes (e.g. K-RAS) or the inactivation of tumors suppressor genes (e.g. TP53) or both. The risk of these genetic mutations may be increased following exposure to environmental components example smoking
Laboratory findings	The pleural fluid typically has a low pH (<7.20), low glucose (<60 mg/dL), and contains infectious organisms. Therefore, the diagnosis relies on the presence of pus or organisms on gram stain. A positive bacteria culture from pleural fluid is not needed to make diagnosis of empyema.	Raised inflammatory markers ( eg high ESR, CRP) are usual but not specific	The most widely used criteria is to differentiate between exudate and transudate using the light's criteria. Fluid is exudate when: Pleural fluid protein/serum protein ratio >0.5 Fluid/serum lactic dehydrogenase (LDH) ratio >0.6 Fluid LDH greater than 2/3 the upper limits of normal of the serum LDH	Laboratory findings are non specific example leukocytosis, sputum samples for gram staining and culture. Other tests include urine antigen test, PCR, C-reactive protein and procalcitonin	The laboratory findings are  non specific including: neutropenia, hyponatremia, hypokalemia, hypercalcemia, respiratory acidosis, hypercarbia, hypoxia, and tumor cells in sputum and pleural effusion cytology.
Physical examination	On examination, the following findings may be seen: Lateral chest wall swelling and tenderness, clubbing of the fingernails, dull percussion note, r educed breath sounds on the affected side of the chest, egophony, coarse crackles, increased tactile fremitus, mediastinal shift to opposite side with large empyema	Chest examination shows features of consolidation such as localised dullness on percussion, bronchial breath sound etc. Dental decay is common especially in alcoholics and children. Clubbing is present in one third of patients.	Bulging of the intercostal spaces, decreased chest expansion bronchovesicular breath sounds of decreased intensity, egophony, dullness to percussion, decreased or absent fremitus.	Physical examination increased respiratory rate, low oxygen saturation, difficulty breathing, bronchial breathe sounds, increased tactile fremitus crackling sounds, or increased whispered pectoriloquy.	Physical examination findings are non specific and may include decreased/absent breath sounds, pallor, low-grade fever, tachypnea and cachezia.
CXR	Chest X ray of empyema shows air-fluid level continuos homogenous pattern from the mediastinum to the chest wall forming obtuse angle with the lung parenchyma.	Chest xray shows often unilateral cavity containing an air-fluid level and consolidation of lung parenchyema.	A homogenous opacification is noted at the affected side. The costophrenic angle is obliterated with a meniscus.	CXR shows areas of diffused opacities.	CXR may show lung mass, widening of the mediastinum, atelectasis, or pleural effusion.
Chest ultrasound	Ultrasound in empyema is positive for suspended microbubble sign, air fluid level, curtains sign and loss of gliding sign.	Ultrasound in lung abscess is negative for suspended microbubble sign, curtains sign and loss of gliding sign but air fluid level may be seen,.	Ultrasonography is helpful in making diagnosis of pleural effusion particularly in differentiating effusion from masses. The extended thoracic spine sign on sonography has high sensitivity and specificity for diagnosing pleural effusion. Chest or upper abdominal ultrasound may show subpulmonic effusion as shown below.	Not reqiured unless complicated with empyema	USG is helpful in guiding biopsy, staging and estimating prognosis. It may show hypo- and hyperechogenic masses.
CT scan	Seen as a lung mass whose cavity is regular with smooth and regular lumen, well-defined boundary and shape changes with change in patient's position. Mass may resolve on antibiotics The split pleura sign is present (most reliable sign to differentiate empyema from lung abscess)	Lung mass whose cavity is rregular with undulated lumen, irregular-poorly defined boundary and shape does not change with change in patient's position. Mass may resolve on antibiotics	In most cases CT imaging may not provide additional information that would influence the clinical decision-making process. CT scan shows heterogeneous opacification of the affected side and cardiomediastinal shift to the opposite site in unilateral effusion.	CT findings in pneumonia include:[1] Airspace consolidation Ground-glass oppacities Pleural effusion Hiliar and/or mediastinal lymphadenopathy Bronchiectasis Tree-in-bud appereance	Seen as a spiculated irregular solid mass that does not resolve on antibiotics