Infections disorders

• In patients with fever, inquire about age, localizing symptoms, weight loss, joint pain, injection drug use, immunosuppression, history of cancer, medications, and travel history.

• Fever is a regulated rise to a new “set point” of body temperature mediated by pyrogenic cytokines acting on the hypothalamus. • The fever pattern is of marginal value, except for the relapsing fever of malaria, borreliosis, and lymphoma (especially Hodgkin disease). • Most febrile illnesses are caused by common infections, are short-lived, and are relatively easy to diagnose. • The term FUO (“fever of undetermined origin”) refers to cases of unexplained fever exceeding 38.3°C on several occasions for at least 3 weeks in patients without neutropenia or immunosuppression. • In HIV-infected individuals, fever may be caused by lymphoma or infections such as disseminated Mycobacterium avium-intracellulare, Pneumocystis jirovecii, cytomegalovirus, or disseminated histoplasmosis. • In a returned traveler, consider malaria, dysentery, hepatitis, or dengue fever.

• Fever is defined as an elevated body temperature above 38.3°C. • The average normal oral body temperature taken in midmorning is 36.7°C (range, 36.0°C–37.4°C). • The normal diurnal temperature variation is 0.5°C to 1.0°C (lowest in the early morning and highest in the evening). • The normal rectal or vaginal temperature is 0.5°C higher; the axillary temperature is 0.5°C lower. • Rectal is more reliable than oral temperature, particularly in tachypneic states. • There is a slight sustained temperature rise following ovulation, during the menstrual cycle, and in the first trimester of pregnancy.

• Infections: bacterial (including tuberculosis), viral, rickettsial, fungal, parasitic • Autoimmune diseases • Central nervous system diseases: head trauma, mass lesions • Malignant disease: renal cell carcinoma, liver cancer (primary or metastatic), leukemia, lymphoma • Cardiovascular diseases: myocardial infarction, thrombophlebitis, pulmonary embolism • Gastrointestinal diseases: inflammatory bowel disease, alcoholic or granulomatous hepatitis • Drug fever • Sarcoidosis • Familial Mediterranean fever • Tissue injury or hematoma • Factitious fever • Peripheral thermoregulatory disorders: heat stroke, malignant hyperthermia of anesthesia, malignant neuroleptic syndrome

• Obtain CBC with differential, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level Urinalysis Liver tests Blood and urine cultures

• Obtain chest radiograph • Consider Abdominal ultrasound and computed tomography Radionuclide-labeled leukocyte, gallium-67, or radiolabeled human immunoglobulin scans

Consider temporal artery biopsy in febrile patients aged 65 years and older with elevated ESR.

• Antipyretic therapy with aspirin or acetaminophen. • After blood and urine cultures, empiric broad-spectrum antibiotics are indicated in patients who are clinically or hemodynamically unstable, neutropenic, asplenic, immunosuppressed, or likely to have significant infection. • Outpatient parenteral antimicrobial therapy can be given to patients with fever and neutropenia after chemotherapy. • If a fungal infection is suspected, add fluconazole or amphotericin B.

• Most fever is well tolerated. • When temperature is 41°C, use alcohol or cold sponges, ice bags and baths, ice-water enemas to reduce the fever.

• Risk factors: sexual contact, needle sharing, transfusion, or perinatal exposure • Prominent systemic complaints such as sweats, diarrhea, weight loss, and wasting • Opportunistic infections caused by diminished cellular immunity • Aggressive cancers, particularly Kaposi sarcoma and extranodal lymphoma • Neurologic manifestations, including dementia, neuropathy, and aseptic meningitis

• Etiology: HIV-1, a retrovirus. • Diagnosis of AIDS generally requires evidence of HIV infection plus the presence of an “AIDS-defining” opportunistic infection or a CD4 count <200 cells/μL.

• HIV-related infections and neoplasms can affect virtually every organ. • Many HIV-infected persons remain asymptomatic for years even without antiretroviral therapy; there is a mean of about 10 years between infection with HIV and development of AIDS. • Symptoms are protean and nonspecific, eg, fever, night sweats, and weight loss. • Shortness of breath, cough, and fever from pneumonia. • Anorexia, nausea and vomiting, and increased metabolic rate contribute to weight loss. • Diarrhea from bacterial, viral, or parasitic infections. • Physical examination findings may be normal or reveal generalized lymphadenopathy. • Conditions highly suggestive of HIV infection: hairy leukoplakia of the tongue, oral and esophageal candidiasis; Kaposi sarcoma, cutaneous bacillary angiomatosis; cytomegalovirus retinitis; tuberculosis and Pneumocystis jirovecii lung infections; many gastrointestinal infections, including Cryptosporidium; central nervous system (CNS) disease, including HIV encephalopathy, progressive multifocal leukoencephalopathy (PML), non-Hodgkin lymphoma, and toxoplasmosis; increased risk of malignancy, including lymphoma and cervical and anal carcinomas.

• Depends on mode of presentation. Constitutional symptoms: cancer, tuberculosis, endocarditis, or endocrinologic diseases such as hyperthyroidism. Pulmonary processes: acute or chronic lung infection, noninfectious pulmonary diseases. Neurologic disease: any other cause of mental status changes or neuropathy. Diarrhea: infectious or antibiotic-associated colitis, inflammatory bowel disease, or malabsorption syndromes.

• HIV antibody by enzyme-linked immunosorbent assay (ELISA), confirmed by Western blot (sensitivity >99.9%; specificity ~100%). • ~95% of persons develop antibodies within 6 weeks after infection. • Absolute CD4 lymphocyte count: as count decreases, risk of serious opportunistic infection increases.

• For P jirovecii pneumonia: chest radiography, Wright-Giemsa stain of induced sputum, bronchoalveolar lavage • For CNS toxoplasmosis: head computed tomography scan, stereotactic brain biopsy • For cryptococcal meningitis: cerebrospinal fluid (CSF) culture, CSF and serum cryptococcal antigen (CRAG) • For HIV meningitis or myelopathy: CSF cell count, lumbar puncture, head magnetic resonance imaging, or CT scan • For AIDS dementia complex, depression: neuropsychiatric testing • For enterocolitis: stool culture and ova and parasite examinations, colonoscopy, and biopsy

• Antiretroviral treatment is now recommended for all HIV-infected persons regardless of CD4 count. • Antiretrovirals should never be used alone as a single agent, and at least three active agents should be used at all times. • Nucleoside reverse transcriptase inhibitors (NRTIs, eg, abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, zidovudine), nucleotide reverse transcriptase inhibitors (eg, tenofovir), and non-nucleoside reverse transcriptase inhibitors (NNRTIs, eg, delavirdine, efavirenz, etravirine, nevirapine, rilpivirine) inhibit the ability of HIV to be transcribed from viral RNA into DNA which is later incorporated into the host genome. • Protease inhibitors (PIs, eg, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, atazanavir, darunavir/ritonavir, tipranavir/ritonavir) block the enzyme necessary to produce new infectious HIV viruses from the host cell. • Entry inhibitors (eg, enfuvirtide, maraviroc) block the binding and entry of the HIV virus into the host cell. • Integrase inhibitors (eg, raltegravir, elvitegravir, dolutegravir) block the ability of the HIV DNA to be integrated into the host genome (after reverse transcription from RNA to DNA). • Most clinicians will start with a single tablet, once-a-day fixed dose combination pill with two reverse transcriptase inhibitors plus either a third reverse transcriptase inhibitor, a PI, or an integrase inhibitor such as (tenofovir/emtricitabine/efavirenz (Atripla), abacavir/lamivudine + efavirenz (Epzicom), or (tenofovir/emtricitabine/rilpivirine (Complera). • Treat fever, anorexia, weight loss, and nausea symptomatically; treat opportunistic infections as indicated. • Treat P jirovecii pneumonia with trimethoprim-sulfamethoxazole (TMP-SMX); prophylaxis when CD4 counts are <200 cells/μL with TMP-SMX, dapsone, or atovaquone. • For Mycobacterium avium-intracellulare complex (MAC) infection, prophylaxis when CD4 counts are below 75 to 100 cells/μL with azithromycin weekly. • For toxoplasmosis, prophylaxis when CD4 counts are below 100 cells/μL with TMP-SMX.

• Acquired during the course of receiving treatment for other conditions more than 48 hours after admission. • Most health care-associated infections are preventable; hand washing is most effective.

• Often result from devices for diagnosis, monitoring, or therapy such as IV catheters, Foley catheters, drainage catheters, orotracheal tubes for ventilation, and duodenoscopes used in cholangiopancreatography; early removal reduces infection. Proper sterilization of equipment used repeatedly with different patients is key. • Often occur in critically ill patients with long hospitalizations and broad-spectrum antibiotic therapy. • Causative organisms are often multidrug resistant and different from those in community-acquired infections: MRSA, Staphylococcus epidermidis, Enterococcus faecium resistant to ampicillin and vancomycin; resistant gram-negative infections caused by Pseudomonas, Citrobacter, Acinetobacter, Stenotrophomonas spp, and Enterobacter, including carbapenem-resistant Enterobacteriaceae (CRE).

• Those of the underlying disease • All infections: fever, tachycardia, tachypnea, hypotension, systemic inflammatory response syndrome (SIRS), sepsis, and septic shock • Ventilator-associated pneumonia: increasing ventilator requirements, focal lung consolidation • Central venous catheter infections: erythema, warmth, drainage at catheter site • C difficile infection: diarrhea

• Noninfectious Drug fever Nonspecific postoperative fevers (tissue damage or necrosis) Hematoma Pancreatitis Pulmonary embolism Myocardial infarction Ischemic bowel • Urinary tract infections • Pneumonia • Other source of bacteremia (eg, abscess, genitourinary or gastrointestinal tract) • Wound infection (eg, pressure ulcer)

• Blood cultures are universally recommended; sputum Gram stain and cultures for pneumonia. • A positive wound culture without signs of inflammation or infection, a positive sputum culture without pulmonary infiltrates on chest radiograph, and a positive urine culture in a catheterized patient without symptoms or signs of pyelonephritis are all likely to represent colonization, not infection.

• Chest radiographs frequently obtained

• Empiric therapy with vancomycin • Empiric gram-negative coverage in patients who are immunocompromised or critically ill • Antibiotic lock therapy for catheter lumens to salvage the catheter

• Remove catheters if There is purulence at the exit site. The organism is S aureus, a gram-negative rod, or Candida spp. There is persistent bacteremia (>48 hours while receiving antibiotics). Complications, such as septic thrombophlebitis, endocarditis, or metastatic abscesses, occur. • Central venous catheters may be exchanged over a guidewire provided there is no erythema or purulence at the exit site and the patient does not appear to be septic.

• Risk factors: preexisting organic heart lesion, prosthetic valve, injection drug use • Fever, new or changing heart murmur, evidence of systemic emboli, positive blood cultures • Evidence of vegetations on echocardiography

• Clinical presentation is dictated by the infecting organism, valve infected, and route of infection. • Acute presentation Caused by more virulent organisms, particularly S aureus Rapidly progressive and destructive infection Acute febrile illnesses Early embolization Acute valvular regurgitation Myocardial abscess • Subacute presentation Caused by viridans strains of streptococci, enterococci, and other gram-positive and gram-negative bacilli, yeasts, and fungi Systemic and peripheral manifestations may predominate • Patients may have underlying cardiac disease, but its prevalence as a risk factor is decreasing. • The initiating event is infection of the valve during bacteremia. • Native valve endocarditis is most commonly caused by S aureus (~40%), viridans streptococci (~30%), and enterococci (5%-10%). • Prosthetic valve endocarditis early after implantation is more likely to be caused by gram-negative organisms, fungi, and both coagulase-positive and coagulase-negative staphylococci. • Injection drug users are more likely to have S aureus and tricuspid valve infection.

• Most present with a febrile illness that has lasted several days to 2 weeks. • Heart murmurs In most cases, preexisting heart murmurs are stable. A new or changing murmur is significant diagnostically, but is the exception rather than the rule. • Characteristic peripheral lesions occur in up to 20% to 25% of patients. Petechiae (on the palate or conjunctiva or beneath the fingernails) Subungual (“splinter”) hemorrhages Osler nodes (painful, violaceous raised lesions of the fingers, toes, or feet) Janeway lesions (painless erythematous lesions of the palms or soles) • Roth spots (exudative, hemorrhagic lesions of the retinas).

• Valvular abnormality without endocarditis Rheumatic heart disease Mitral valve prolapse Bicuspid or calcific aortic valve • Flow murmur (anemia, pregnancy, hyperthyroidism, sepsis) • Atrial myxoma • Noninfective endocarditis, such as systemic lupus erythematosus (Libman-Saks endocarditis), marantic endocarditis (nonbacterial thrombotic endocarditis) • Acute rheumatic fever • Vasculitis • Hematuria from other causes, such as glomerulonephritis or renal cell carcinoma

• Blood culture is the most important diagnostic tool; three sets from different sites before antibiotics maximizes yield. • Leukocytosis in acute endocarditis, anemia of chronic disease in subacute cases. • Hematuria, proteinuria, or renal dysfunction from emboli or glomerulonephritis. • Duke criteria for the diagnosis of infective endocarditis. Major criteria: two positive blood cultures with typical microorganism, positive echocardiogram findings, and new regurgitant murmur Minor criteria: predisposing condition, fever >38°C, embolic disease, immune phenomena (Osler nodes, Janeway lesions, Roth spots, glomerulonephritis, rheumatoid factor), positive blood cultures with an organism not meeting major criteria, or serologic evidence of active infection with an organism that causes endocarditis 80% accuracy with two major, one major and three minor criteria, or five minor criteria Possible endocarditis with one major and one minor or three minor criteria Endocarditis unlikely if criteria are not met and fever abates within 4 days or alternative explanation for illness is found

• Chest radiography may show an underlying cardiac abnormality or embolic infiltrates in right-sided endocarditis. • Transthoracic echocardiography has only a 55% to 65% sensitivity, so it cannot rule out endocarditis. • Transesophageal echocardiography has a 90% sensitivity and can detect myocardial abscess.

• Conduction abnormalities on electrocardiography may suggest myocardial abscess formation.

• Antibiotic therapy should be targeted to causative organism and susceptibilities. • Antibiotics are usually continued for at least 2 to 6 weeks. • Penicillin-resistant organisms may be treated with vancomycin. • Groups B, C, and G streptococci and enterococcal infections may require addition of gentamicin to antibiotic regimens. • For methicillin-susceptible S aureus, nafcillin, or oxacillin is preferred. • For HACEK (Haemophilus aphrophilus [now Aggregatibacter aphrophilus], Actinobacillus actinomycetemcomitans [now Aggregatibacter actinomycetemcomitans], Cardiobacterium hominis, Eikenella corrodens, and Kingella spp) organisms, high-dose ceftriaxone is preferred.

• Indications for valve replacement include valvular regurgitation with acute heart failure, infections that do not respond to appropriate antimicrobial therapy, infection of sinus of Valsalva or septal abscesses, fungal or gram-negative bacilli infections, and continued embolization despite antibiotic treatment.

Colonoscopy should be done to exclude colon cancer in patients with Streptococcus bovis endocarditis.

• Fever, tachycardia, elevated white blood cell (WBC) count, or increased respiratory rate • Proven or probable source of infection; bacteremia with positive blood cultures • Elevated lactate or end-organ dysfunction in severe disease; hypotension in septic shock

• Fevers and chills, often with an abrupt onset. • Hyperventilation with respiratory alkalosis. • Altered mental status. • Hypotension and shock are late findings and poor prognostic signs. • Symptoms and signs of infectious source (eg, abdominal or urinary symptoms, pneumonia).

• Gram-positive versus gram-negative sepsis • Fungal or acid-fast bacillus infection • SIRS from another cause: trauma, burns, pancreatitis, myocardial or bowel ischemia, adrenal insufficiency, pulmonary embolism, aortic aneurysm rupture, anaphylaxis, toxin ingestion • Shock from another cause: cardiogenic, neurogenic, hypovolemic, anaphylactic

• Complete blood count may show neutropenia or neutrophilia and immature polymorphonuclear leukocytes (“bands”). • Thrombocytopenia; elevated lactic acid; coagulation dysfunction with or without disseminated intravascular coagulation (DIC). • Three blood cultures should be obtained before starting antimicrobials, if possible.

• Chest radiography to look for pulmonary infection

procedural findings in sepsis?

• Antibiotic therapy should be given as soon as the diagnosis is suspected because delayed antibiotic therapy leads to increased mortality rates. • Initially, give broad-spectrum antibiotic therapy; narrow antibiotics based on culture and sensitivity data. • Give aggressive IV fluids and vasopressors to maintain blood pressure if needed using a goal-directed therapy protocol early to target hemodynamic goals. • Stress-dose hydrocortisone may benefit patients with severe septic shock but is unlikely to benefit those with less-severe septic shock.

May be required to control source of bacteremia, depending on the etiology

Drainage or removal of source of bacteremia (eg, central venous catheter removal, abscess or empyema drainage)