infection 594 Cryptococcus neoformans causes pneumonia and/or disseminated disease with fungemia and meni ngitis, or pneumonia. Risk factors are advanced HIV, solid organ transplantation, and other chronic immunosuppressing conditions (e.g., long-term corticosteroid use). Presentation: T he history may be subacute and there may be features suggesting elevated intracranial press ure (e.g., confusion, papilledema, cranial nerve palsies). Diagnosis: Serum and CSF cryptoc occal antigen; India ink CSF staining; and blood, sputum, and CSF culture. All immunocompro mised patients require evaluation of CSF that includes pressure measurement. Treatment: Amp hotericin B deoxycholate 0.7 \200\2231.0/kg/d (or liposomal 3 \200\2234 mg/kg/d) IV + flucy tosine 25 mg/kg/6 h PO \227 14 d or longer, then fluconazole 400 \200\223800 mg/d \227 8 wks or longer, then 200 mg/d until CD4 >200 \227 6 months (AIDS patients). If CSF opening pressure (OP) is >250 mm H 2 O, drain CSF until OP decreases 50%. Repeat drainage daily unt il OP is <200. Failure to do this is an important cause of morbidity and mortality due to c ryptococcal meningitis. Fluconazole at 400 mg/d for 6 \200\22312 months can be used in pati ents with mild to moderate pulmonary disease only (CSF evaluation required). Other fungi ca using deep infection Histoplasma capsulatum, Coccidioides immitis, Paracoccidioides brasili ensis , and Blastomyces dermatitidis may cause asymptomatic infections, acute or chronic lu ng disease, or disseminated infection. Acute histoplasma pneu- monitis is associated with a rthralgias, erythema nodosum, and erythema multiforme. Chronic disease may cause upper-zone fibrosis or radiographic \200\234coin lesions. \200\235 Diagnosis: CXR, serology, culture , and biopsy. When severe (usually in immunocompromised patients), treatment is with an amp hot- ericin B formulation. After stabilization or when mild to moderate, these diseases are treated with itraconazole, except coccidioidomycosis, which may be treated with fluconazol e (especially with cocci meningitis). s e s a e s i d s u o i t c e f n I Preventing fungal infections This is a goal in the immunocompromised. Fluconazole, posacona zole, voriconazole, and topical nystatin have roles in prevention of infection depending on risk factors (e.g., cytotoxic chemotherapy, solid organ trans- plantation, bone marrow tra nsplant, and as secondary prophylaxis after cryptococcal meningitis in HIV patients). Decis ions regarding prophylaxis depend on knowledge of risk factors. 595 Table 14.31 Fungal prophylaxis Infection Candidiasis Patient type Oropharyngeal: HIV, radiation therapy, cytotoxic chemotherapy, poor-fitting dentures Vulvovaginal: Antibiotics, DM, otherwise healthy women Disseminated: Central venous catheters, cytotoxic chemotherapy, neutropenia, abdominal surg ery, burns, parenteral nutrition Aspergillosis Invasive disease in those with neutropenia, trans- plant, corticosteroids, chronic granulom atous disease (CGD). Cryptococcosis Mucormycosis HIV, transplant, corticosteroids, lymphoma Neutropenia, transplant, uncontrolled DM, deferoxamine Histoplasmosis Exposure in endemic areas (e.g., Ohio River Valley), usually a self limited disease. Disseminated disease in those with risks similar t o cryptococcosis Coccidioidomycosis Exposure in endemic area (e.g., Southwestern United States, California \200\231s Central Va lley), usually a self limited disease (valley fever). Disseminated disease in those with ri sks similar to cryptococcosis Rare filamentous fungal infections Fusarium, Scedosporium, Ochroconis, and many others: Risk for invasive disease similar to a spergillosis Table 14.32 Treatment of fungal infections Antifungal Typical use Typical dose (normal GFR) Loading dose: 800 mg \227 1 then 400- mg/d (IV or PO). Lower dos es oral candidi- asis, 150 mg \227 1 for vulvovaginal disease Renal adjust- ment required Toxicity Fluconazole Liver, drug Candida, interactions, Cryptococcosis, Coccidioides 596 (Continued) s e s a e s i d Table 14.32 (Continued) Antifungal Typical use Typical dose (normal GFR) IV: Loading Toxicity Voriconazole Aspergillus, can- Liver, CNS, skin, QT, multiple drug interactions s u o i t c e f n I dida , other fila- mentous fungal infections (not mucormycosis) dose of 6 mg/ kg/12 h \227 2 then 4 mg/ kg/d Caution with IV solution with GFR <50; cyclo- dextrin vehicle may cause renal accumulate an d exacerbate renal damage PO: Loading dose: 400 mg/12 h \227 2, then 200 mg/12 h. Decrease doses by 50% for patients <40 kg Posaconazole Aspergillus, Candida , mucormycosis (not first line) Histoplasmosis, blastomycosis 200 mg/8 h PO Liver, QT, multiple drug interactions Itraconazole 200 mg/12 h PO. Oral solution bet- ter absorbed than tabs Anidulafungin: 200 mg \227 1, th en 100 mg/d IV Liver, GI upset, negative ino- trope, QT, drug interactions Echinocandins Candida, Histamine release, Aspergillus (not first line) liver Caspofungin: 70 mg \227 1, then 50 mg/d IV Micafungin 100 mg/d IV Deoxycholate Amphotericin B (AmB) Candida, Infusion reac- Aspergillus , mucormycosis, Cryptococcus, Histoplasma, Coccidioides AmB: 0.7 \200\2231.0 mg/kg/d IV tion, renal and electrolyte Liposomal 597 AmB: 3 \200\2236 mg/kg/d IV (less toxic than deoxycholate) Flucytosine (5-FC) Used as part of combina- tion therapy with AmB for cryptococcosis 25 mg/kg/6 h Renal adjust- ment required Myelo suppression colitis, hepatitis Nematodes (roundworms) Worldwide, 1 billion people are hosts to nematodes. Ascariasis can cause GI obstruction, hookworms can stunt growth, necatoriasis can cause debili- tating ane mia, and trichuriasis causes dysentery and rectal prolapse. Mass population treatment (e.g. , albendazole 400 mg/24 h PO for 3 d) to school children or immigrants from endemic areas m ay be beneficial. Necator americanus and Ankylostoma duodenale (hookworms) Occur in the Ind ian subcontinent, Southeast Asia, Central and North Africa, and parts of Europe. Necator is also found in the Americas and sub-Saharan Africa. Presentation: Numerous small worms atta ch to upper GI mucosa, causing bleeding and consequent iron-deficiency anemia. Eggs are exc reted in the feces and hatch in soil. Larvae penetrate feet, thus starting new infections. Oral transmission of Ankylostoma may occur. Diagnosis: Stool microscopy. Treatment: Mebenda zole 100 mg/12 h PO for 3 d, and iron. Strongyloides stercoralis is endemic in the (sub) tr opics. Transmission: Percutaneous. Presentation: Causes rapidly migrating urticaria over th ighs and trunk ( cutaneous larva migrans ). Pneumonitis, enteritis, and malabsorption may o ccur. Chronic signs: Diarrhea, abdominal pain, and urticaria. The worms may take bacteria i nto the bloodstream, causing gram-negative bacterial septicemia meningitis. Diagnosis: S tool microscopy and culture, serology, or duodenal aspiration. Treatment: Ivermectin 200 mc g/kg/d \227 2 or albendazole 400 mg/12 h PO for 7 d. Hyperinfestation is a problem if immu nocompromised (e.g., on steroids, or, more rarely, in AIDS). Therapy may need to be prolong ed or repeated in immunocompromised patients. Ascaris lumbricoides occurs worldwide. It loo ks like (and is named after) the garden worm ( Lumbricus ). An unusual characteristic is th at it has three finely toothed lips. Transmission: Fecal \200\223oral. It migrates through liver and lungs, then settles in the small bowel. It is usually asymptomatic, but death may occur from GI obstruction or perforation. If a worm migrates into the biliary tract, chola ngitis or pancreatitis can result. A worm may grow very long (e.g., 25 cm). Diagnosis: Stoo l microscopy shows ova (stained orange by bile); worms on barium x-rays; eosinophilia (may be absent if immunosuppressed). Treatment: Mebendazole 100 mg/12 h PO for 72 h or ivermecti n 150 \200\223200 mcg/kg \227 1. Trichinella spiralis occurs worldwide and is transmitted by uncooked pork. Presentation: It migrates to muscle, causing myalgias, myocarditis, and p eriorbital edema fever. Treatment: Albendazole 400 mg/12 h PO for 8 \200\22314 d, with c oncomitant prednisolone 40 mg/d PO. Alternative is mebendazole 200 \200\223400 mg/8 h \227 72 h, then 400 \200\223500 mg/8 h \227 10 d. Trichuris trichiura (whipworm) may cause non specific abdominal symptoms. Diagnosis: Stool microscopy. Treatment: Mebendazole 100 mg/12 h PO or ivermectin 200 mcg/kg PO \227 3 d. Enterobius vermicularis (pinworm) is common in temperate climes. Presentation: It causes anal itch as it leaves the bowel to lay eggs on t he perineum. Apply sticky tape to the perineum and identify eggs microscopically. Treatment : Mebendazole 100 mg PO. Repeat at 2 wks if >2 yrs and treat the whole family. Hygiene is m ore important than drugs as adult worms die after 6 wks. Continued symptoms suggest a reinf ection. Toxocara canis Most common cause of visceral larva migrans . The infection presents with eye granulomas (squint, blindness, pigmentary retinopathy) or visceral involvement (f ever, myalgias, hepatomegaly, asthma, cough). Diagnosis: Ophthalmoscopy, serology, may requ ire histology. Treatment: Albendazole 400 mg/12 h \227 5 d or mebendazole 100 \200\223200 mg/12 h \227 5 d. In ocular disease, visible larvae can sometimes be photocoagulated by la ser. Systemic or topical ocular steroids may be 598 needed to control eye inflammation. Toxocara is commonly acquired by ingesting soil contami nated by animal feces so de-worm pets regularly and exclude them from play areas. s e s a e s i d Filarial infections Onchocerciasis is caused by Onchocerca volvulus and is transmitted by t he black fly. Presentation: It causes river blindness in parts of Africa and South America. Worldwide, 37 million are affected, 500,000 have visual impairment, and 270,000 are blind ed by this pathogen. Initially, a nodule forms at the site of the bite, shedding microfilar iae to distant skin sites, which develop altered pigmentation, lichenification, loss of ela sticity, and poor healing. Disease manifestations are mainly due to the localized host resp onse to dead/dying microfilariae. Eye manifestations include keratitis, uveitis, cataract, fixed pupil, fundal degeneration, or optic neuritis/atrophy. Lymphadenopathy and elephantia sis also occur. Diagnosis: Visualization of microfilaria in eye or skin snips. Remove a fin e shaving of clean, unanesthe- tized skin with a scalpel. Put on slide with a drop of 0.9% saline and look for swimming larvae after 30 min. Treatment: Seek expert help. Ivermectin i s the drug of choice (e.g., 1 dose of 150 mcg/kg PO repeated, e.g., every 6 months for Onch ocerca ). Ivermectin does not kill adult worms so treat- ment needs to be repeated every 6 months. Length of therapy depends on symptoms, eye findings, and ongoing presence of microf ilaria in skin. Doxy- cycline 200 mg/d \227 6 wks may help by killing Wolbachia , an endos ymbiont of adult worms. Must rule out Loa loa before giving ivermectin as fatal encephaliti s may ensue. Lymphatic filarial Affects 120 million worldwide and occurs in Asia, Africa, S outh America, and parts of the Caribbean (Haiti, Dominican Republic). Mosquito vectors tran smit the infection. Acute infections cause fever and lymphadenitis. Wuchereria bancrofti ca uses lower limb lymphedema (elephantiasis) and hydroceles. Brugia malayi causes elephantias is below the elbow/knee. Wuchereria life cycle: A mosquito bites an infected human \206 \222 ingested microfilariae develop into larvae \206\222 larvae migrate to mosquito \200 \231s mouth \206\222 mosquito bites another human \206\222 Wuchereria gains access to blo odstream \206\222 adult filariae lodge in lymphatic system. Lymphedema occurs after initia l infection. Diagnosis: Blood movie (draw blood at night to coincide with organisms \200 \231 nighttime periodicity), serology. A rapid immunochromatographic finger-prick test has been developed for use in the field. Complications: Immune hyperreactivity may cause tropic al pulmonary eosinophilia (TPE) with cough, wheeze, lung fibrosis, eosinophilia, elevated I gE and IgG. Treatment: Diethylcarbamazine (DEC) 6 mg/kg/d \227 1 day for early lymphatic d isease and 14 \200\22321 d for TPE. Ivermectin is effective against W. bancrofti microfilar ia, but not adult worms. Late disease manifestations are not amenable to antiparasitic ther apy, but may improve with elevation and management by a lymphedema specialist. DEC is avail able from CDC. Must rule out O. volvulus infection, as DEC can cause blindness with this pa thogen. Also DEC must be used with care in patients with Loa loa; see below. Loiasis is cau sed by Loa loa . It occurs in West and Central Africa and is transmitted by the Chrysops fl y. It causes painful \200\234Calabar \200\235 swellings of the limbs and eosinophilia, and may migrate across the conjunctiva. Diagnosis: Blood movie (draw around noontime), serolog y, and identification of worm in eye or from skin. Treatment: Seek expert help and treat sy mptomatic patients depending on microfilaria (MF)/m L counts. <8,000: DEC 3 mg/kg/8 h \227 21 d, 8,000 albendazole 200 mg/12 h until <8,000, then complete 21 d with DEC. If avail able, consider apheresis for >8,000. DEC can be obtained from CDC. It must be used with cau tion due to risk for fatal encephalitis s u o i t c e f n I 599 with high Loa loa counts. Steroids may help. Must rule out O. volvulus infection as DEC can cause blindness with this pathogen. Cestodes (tapeworms) Taenia solium (pork tapeworm) infection occurs by eating uncooked pork . T. saginata is contracted from uncooked beef. Both cause vague abdominal symptoms and mal absorption. Sometimes worms can become lodged in appendix or biliary or pancreatic ducts. P atients may report seeing worm parts in stool. Diagnosis is by examination of stool specime n. Treatment is with praziquantel 5 \200\22310 mg/kg \227 1 or niclosamide 2 g \227 1. Us e praziquantel with caution in those who also have cysticercosis (see below). Larval cysts of T. solium are the cause of cysticercosis. Transmission is by ingestion of food or water contaminated with eggs fecally shed from a person who is infected with T. solium worms. Aut oinoculation by fecal \200\223oral route is possible. In the intestine, the eggs mature, pe netrate the circulation, and disseminate throughout the body, encysting in muscle, skin, he art, eye, and CNS, causing focal signs. Subcutaneous cysticercosis causes palpable sub- cut aneous nodules in the arms, legs, and chest. Ocular cysticercosis causes conjunctivitis, uv eitis, retinitis, choroid atrophy, and blindness. Neurocysticercosis is the most common cau se of seizures in some places (e.g., Mexico). Other features: Focal CNS signs (e.g., hemipl egia), odd be- havioral, dementia \200\224or no symptoms. Cysticerci may cluster like bunch es of grapes ( \200\234racemose \200\235 form) in the ventricles (causing hydrocephalus) an d basal cisterns (causing basal meningitis, cranial nerve lesions, and raised ICP). Spinal cysticerci may cause radicular or compressive spinal symptoms. Diagnosis: Usually diagnosed by appearance on neuroimaging and clinical history. Stool microscopy and examination of pe rianal swabs is reserved for difficult cases. Serology: Indirect hemagglutination test. CSF : May show eosinophils in neurocysticercosis, and a CSF antigen test is available. X-rays o f soft tissues may show calcified cysts. Treatment: Antihelminthic therapy will not treat d ead worms (in calcified cysts). Active parenchymal disease: Anticonvulsants for cysticercos is associated seizure disorder, albendazole 7.5 mg/kg/12 h PO with food, or praziquantel 17 mg/kg/8 h PO for 15 d. Treatment duration may need to be longer in patients with extensive or extraparenchymal (e.g., ventricle) disease. An inflammatory response to the dying larva e may require corticosteroids. Dexamethasone 6 mg/d may be effective at reducing seizures w hen used with antiparasitic therapy. If CSF ventricles are involved, consult neurosurgeon t o evaluate for cyst removal and shunt before starting drugs. Antiparasitic drugs may worsen the acute phase of cysticercosis encephalitis. Diphyllobothrium latum is a fish tapeworm a cquired from uncooked fish. It causes similar symptoms to T. solium and is treated with pra ziquantel 5 \200\22310 mg/kg \227 1. It is a cause of vitamin B 12 deficiency. Hymenolepis nana and H. diminuta (dwarf tapeworms) are rarely symptomatic. Treat with praziquantel (25 mg/kg PO). Hydatid disease Cystic hydatid disease is a zoonosis caused by ingesting eggs o f the dog parasite Echinococcus granulosus (e.g., in rural sheep-farming regions). Hydatid is a public health problem in parts of China, Russia, Alaska, Wales, and Japan. Presentatio n: Most cysts are asymptomatic, but liver cysts may present with hepatomegaly, obstructive jaundice, cholangitis, or FUO. Lung cysts may present with dyspnea, chest pain, hemoptysis, or anaphylaxis. Parasites migrate almost anywhere (e.g., CNS or incidentally on CXR). Diag nosis: Plain x-ray, ultrasound, and CT of cysts. A reliable serological test has replaced t he variably sensitive Casoni intradermal test. Treatment: Seek expert help. The drug of cho ice is albendazole 400 mg/12 h/d for 1 \200\2236 months. A common approach is to excise/dra in symptomatic 600 cysts, but beware spilling cyst contents (causes anaphylaxis; praziquantel may be useful pr esurgery of in case of spill). Chemotherapy + the PAIR approach is increasingly replacing s urgery: Puncture, aspirate cyst, inject hypertonic saline, and reaspirate. Give albendazole pre- and postdrainage to prevent recurrence. Note: Alveolar hydatid is caused by E. multil ocularis .) s e s a e s i d s u o i t c e f n I Trematodes (flukes) Schistosomiasis (bilharzia) is the most prevalent disease caused by flu kes, affecting 200 million people worldwide. Most are in Africa. The snail vectors release cercariae that can penetrate the skin (e.g., during swimming or walk- ing in contaminated w ater). This may cause an itchy papular rash ( \200\234swimmer \200\231s itch \200\235). The cercariae shed their tails to become schistosomula and migrate via lungs to liver where th ey grow. 2 wks after initial infestation, there may be fever, urticaria, diarrhea, cough, wheeze, and hepatosplenomegaly ( \200\234Katayama fever \200\235). In 8 wks, mature flukes couple and migrate to resting habitats; that is, vesical veins ( S. hematobium ) or mesent eric veins ( S. mansoni and S. japoni- cum ). Eggs released from these sites can cause gran ulomata and scarring. Clinical schistosomiasis is caused by an allergic response to the egg s. Presentation is likely to have visited or be from Africa, the Middle East, or Brazil ( S . mansoni ) and present with abdominal pain and stomach upset, and, later, hepatic fibrosis , granulomatous inflammation, and portal hyperten- sion (transformation into true cirrhosis has not been well-documented). S. japonicum , often the most serious, occurs in Southeast Asia, tends to affect the bowel and liver, and may migrate to lung and CNS ( \200\234travel ers \200\231 myelitis \200\235). Urinary schistosomiasis ( S. hematobium ) occurs in Africa , the Middle East, and the Indian Ocean. Signs: Frequency, dysuria, hematuria ( hematospe rm- ia), incontinence. It may progress to hydronephrosis and renal failure. There is an inc reased risk of squamous cell carcinoma of the bladder. Diagnosis is based on finding eggs i n the urine ( S. hematobium ) or feces ( S. mansoni and S. japonicum ) or rectal biopsy (al l types). Radiographs may show bladder calcification in chronic S. hematobium infection. Re nal ultra- sound identifies renal obstruction, hydronephrosis, thickened bladder wall. Schi stosoma ELISA is most sensitive. Treatment: Praziquantel: 40 mg/kg PO with food divided int o 2 doses sepa- rated by 4 \200\2236 h for S. mansoni and S. hematobium , and 20 mg/kg/8 h for 1 d in S. japonicum . Sudden transitory abdominal pain and bloody diarrhea may occur sh ortly after. Fasciola hepatica (liver fluke) is spread by sheep, water, and snails. It caus es hepatomegaly, then fibrosis. People usually become infected after eating raw watercress from endemic areas. Presentation is with fever, abdominal pain, diarrhea, weight loss, jaun dice, and eosinophilia. Tests: Stool microscopy, serology. Treatment: Get help. Treat with triclabendazole 10 mg/kg PO \227 1 (may repeat once). This medication is available from CD C. A possible alternative is nitazoxanide 500 mg/12 h \227 7 d. Opisthorchis and Clonorchi s are liver flukes common in the Far East, where they cause cholangitis, cholecystitis, and cholangiocarcinoma. Eating raw or undercooked fresh water fish from endemic areas can caus e this infection. Tests: Stool microscopy. Treatment: Praziquantel 25 mg/kg/8 h PO for 1 d. Fasciolopsis buski is a big intestinal fluke, 7 cm long, causing ulcers or abscesses at t he site of attachment. Eating raw or undercooked aquatic plants from endemic areas can caus e disease. Treatment is as for opisthorchiasis. Paragonimus westermani (lung fluke) is cont racted by eating raw freshwater crabs or crayfish. Presentation: Parasites migrate through gut and diaphragm to invade the lungs, causing cough, dyspnea, and hemoptysis. Secondary co mplications: Lung abscess and bronchiectasis. It occurs in the Far East, 601 South America, and the Congo, where it is commonly mistaken for TB (similar clinical and CX R appearances). Tests: Ova in sputum. MRI/CT may disclose CNS/lung lesions. Treatment: Praz iquantel (25 mg/kg/8 h PO for 2 d) or bithionol (30 \200\22350 mg/kg on alternate days PO f or 10 d). With cerebral disease, a short dose of corticosteroids may help to decrease infla mmatory response to dying parasites when praziquantel is given. Exotic infections Exotic infections may be community-acquired or nosocomial (acquired in ho spital). The increased prevalence of immunosuppression, both drug- induced and innate, inte rnational travel, human encroachment on animal habitats, and the widespread use of broad-sp ectrum antibiotics have led to increases in rates of exotic infections. New techniques such as PCR have enabled the identification of more putative infective agents. History When an infection is suspected (fever, sweats, inflammation, diarrhea and vomiting, WBC elevation, or any unexplained symptom), ask the patient about: \212 Foreign travel Artificial implant able material (e.g., hip prosthesis, prosthetic heart \212 valves) Risk factors for HIV Tr eatment with immune modulator, steroids, transplantation Necrotic tissues Pets Animal expos ure (including insects) Sick contacts \212 \212 \212 \212 \212 \212 Diagnosis Take appropriate cultures (blood, urine, stoo l, CSF) or swabs as clinically indicated. Consult early with an infectious diseases physici an. Consider CXR, ultrasound, or CT as clinically indicated. If the infection appears to be localized, consider surgical debridement drainage. Do not give up if you cannot culture an organism; tests may need to be repeated. Perhaps the organism is \200\234fastidious \200\235 in its nutritional requirement or requires prolonged incubation? Even if culture i s achieved, it may be that the organism is pathogenic, or it could be a commensal (i.e., pa rt of the normal flora for that patient). If culture is not possible, look for antibodies o r antigen in the serum or other body fluids. It is generally agreed that a fourfold increas e in antibody titers in convalescence (compared with the acute sera) is indicative of recen t infection, although not diagnostic. PCR is increasingly being used to make identification s; however, it is far from infallible, and contamination with DNA from the lab or elsewhere is a potential problem. Treatment Table 14.33 suggests treatment options, but it is only a guide, as susceptibility patterns may vary be local epidemiological patterns. Consult with local microbiologist and/or Infectious Diseases specialist. 602 Table 14.33 Treating exotic infections Organism Acanthamoeba spp. (free living amoeba) Site or type of infection Keratitis Treatment example Topical chlorhexidine or polyhexamethylene biguanide propamidine iseth ionate Pentamidine + azole + TMP/SMX flucytosine Carbapenems, aminoglycosides, colistin CNS disease UTI, CSF, lung, bone, bloodstream, conjunctiva IE, CNS, UTI, bone, thyroid, lun g, periodontitis, abscesses Penicillin, third-generation ceph gentamicin Acinetobacter complex Actinobacillus actinomycetemcomitans Actinobacillus lignieresii Actinobacillus ureae Aerococcus viridans Aeromonas hydrophila Af ipia broomeae Alcaligenes species Angiostrongylus cantonensis CSF, IE, wounds, bone, lymph nodes Bronchus, CSF post-trauma, hepatitis Empyema, UTI, CSF, bone IE, CSF, cornea, bone, D&V, liver abscess Marrow, synovium Dialysis peritonitis, ear, lung Eosinophilic meningitis Ampicillin, third-generation ceph gentamicin Ampicillin, third-generation ceph gentam icin Penicillin gentamicin Gentamicin, ciprofloxacin Imipenem or ceftriaxone Amox/clav, piperacillin/tazobactam, cefepime, TMP/SMX Corticosteroids albendazole (rat lung worm) Arcanobacterium Babesia microti (protozoa) Bacillus cereus Balamuthia mandrillaris (free li ving amoeba) Baylisascaris procyonis (rac- Throat, cellulitis, leg ulcer FUO hemolysis if old/splenectomized Wounds, eye, ear, lung , UTI, IE CNS, skin, adrenals, kidneys Azithromycin, doxycycline, clindamycin, quinolones Atovaquone + azithromycin Vancomycin Pen tamidine + macrolide + sulfadiazine + flucytosine + fluconazole Eosinophilic meningoencephalitis Albendazole + corticosteroids coon roundworm) (Continued) Infectious diseases 6 0 3 6 0 4 Table 14.33 (Continued) Organism Bifidobacterium Bordetella bronchiseptica Burkholderia cepacia , etc Site or type of infection Vagina, UTI, IE, peritonitis, lung URTI, CSF (after animal contac t) Wounds, lungs (esp. in CF), IE, CAPD, UTI, ecthyma Treatment example Penicillin Doxycycline. TMP/SMX Ceftazidime, minocycline, meropenem (formerly Pseudomonas ) Burkholderia pseudomallei (formerly Pseudomonas ) gangrenosa, peritonitis Melioidosis: Self-reactivating septicemia + multiorgan, protean signs (e.g., in rice farmer s, via water/soil in Southeast Asia) Ceftazidime TMP/SMX, meropenem Capnocytophaga canimorsus Cellulitis, sepsis with DIC in asplenics Capnocytophaga ochracea Ampicillin/sulbactam Penicillin or ciprofloxacin Oral ulcer, stomatitis, arthritis, blood, cervical abscess and C. sputagena Cardiobacterium hominis IE Chromobacterium violaceum Nodes, eye, bone, liv er, pustules Citrobacter koseri/diversus Corynebacterium jeikeium Corynebacterium striatum Corynebacterium ulcerans Cyclospora cayetanensis Edwardsiella tarda Penicillin + gentamicin Quinolones, TMP/SMX, imipenem Cephalosporins Vancomycin Vancomycin, non-PCN \222 -lactams Penicillin + diphtheria antitoxin TMP/SMX Cephalosporins + gentamic in CSF, UTI, blood, cholecystitis Fever/sepsis in neutropenia Indwelling device infection Diph theria-like CNS signs Diarrhea (via raspberries) Cellulitis, abscesses, BP \206\223 , d ysentery via penetrating fish injuries Eikenella corrodens Sinus, ears, PE postjugular vein phlebitis (postanginal Penicillin gentamicin, Resistant to metronidazole sepsis) via bites and clindamycin Elizabethkingia Lungs, epidemic neonatal meningitis, postop bacteremia TMP/SMX, minocycline, quinolone or vancomycin + meningosepticum rifampin Erysipelothrix rhusiopathiae Erysipelas-like, IE Finegoldia magna Fusobacterium necrophorum Gemella haemolysans Gnathostoma spinigerum Penicillin Penicillin, imipenem Clindamycin, ampicillin/sulbactam Penicillin + gentamicin I vermectin or albendazole Bone, joint, wound, teeth, face Jugular venous septic thrombophlebitis IE, meningitis after neurosurgery Migrating subcutaneous lesions with eosinophilia, CNS (helminth) disease Helicobacter cinaedia Kingella kingae Lactobacillus Mobiluncus curtisii/mulieris Vagina, ut erus, septicemia in cirrhosis Moraxella osloensis and M. Proctitis in homosexual men Throat, larynx, eyelid, joint, skin Teeth, chorioamnionitis, py elitis Ampicillin or gentamicin Third-generation cephalosporin, gentamicin Penicillin gentam icin, clindamycin Cephalosporins or ampicillin Penicillin Conjunctiva, wound, vagina, UTI, CSF CNS, bone, hem- nonliquefaciens orrhagic stomatitis Meningoencephalitis Naegleria fowleri (free living Amphotericin B IV AmB by IT, azole, rifampin amoeba) Neisseria cani Neisseria cinerea/mucosa ; N. subflava; N. flavescens Wounds from cat bites IE, CNS, bone, post human bites or from peritoneal Amoxicillin Penicillin, cephalosporin dialysis Pasteurella multocida Bone, lung, CSF, UTI, pericarditis epiglottitis. Post cat/ Amoxicillin/clavulanate, doxycycline dog bite Pasteurella pneumotropica Wounds, joints, bone, CSF Penicillin, cephalosporins (Continued) 6 0 5 Infectious diseases 6 0 6 Table 14.33 (Continued) Organism Plesiomonas shigelloides Propionibacterium acnes Site or type of infection D&V, eye, sepsis post fishbone injury Face, wounds, CSF shunts, b one, IE liver granuloma Treatment example Ciprofloxacin, TMP/SMX Penicillin, vancomycin, doxycycline, clindamycin (botryomycosis) Prototheca wickerhamii/ Subcutaneous granuloma, bursitis lymphadenitis, nodules, Amphotericin or azoles zopfii (achlorophyllous algae) granuloma Providencia stuartii Ralstonia pickettii Rhodococcus equi Rothia dentocariosa Serratia marc escens UTI, burn or lung infections CSF, lungs, blood in ICUs Lung, CNS, wounds Appendix abscess W ound, burns, lung, UTI, liver, CSF, bone, IE, red diaper Carbapenems, piperacillin/tazobactam, gentamicin Cephalosporin Vancomycin, meropenem + rifa mpin or Cipro Penicillin, vancomycin Imipenem, ceftazidime, ciprofloxacin syndrome Shewanella (Pseudomonas) CSF post CNS surgery/head trauma Advanced-generation Cephalosporins putrefaciens Sphingobacterium multivorum Peritonitis (spontaneous) Cephalosporins, carbapenems, TMP/SMX Sphingomonas paucimobilis Stenotrophomonas maltophilia Superficial leg ulcer, CSF, UTI Wounds, ear, eye, lung, UTI, IE Ceftazidime, imipenem TMP/SMX, levofloxacin, ticarcillin/clavulanate Staphylococcus lugdunensis Streptococcus bovis Tropheryma whipplei Vibrio vulnificus IE, in fective endocarditis; D+V, diarrhea and vomiting; CNS, central nervous system; UTI, urinary tract infection; URTI, upper respiratory tract infection IE, skin, bone, prosthetic devices IE if colon cancer, do colonoscopy Whipple \200\231s dis ease (GI, CNS, lymphadenopathy, FUO, IE) PCN, ceftriaxone Wounds, muscle, uterus, fasciitis Oxacillin, vancomycin Penicillin + gentamicin Doxycycline + ceftazidime 6 0 7 Infectious diseases Hematology Alison R. Moliterno , M.D. y g o o t a m e H l Contents Anemia 608 Iron-deficiency anemia 609 The anemia of chronic disease 610 Sideroblastic anemi a 610 The peripheral blood movie 611 The differential white cell count 612 Macrocytic anemi a 613 Pernicious anemia 614 An approach to hemolytic anemia 615 Causes of hemolytic anemia 616 Sickle-cell anemia 617 Thalassemia 619 Bleeding disorders 620 The intrinsic and extrins ic pathways of blood coagulation 621 Coagulation tests 622 Anticoagulants 623 Leukemia and the resident 625 Acute lymphoblastic leukemia 626 Acute myeloid leukemia 627 Chronic myeloi d leukemia 628 Chronic lymphocytic leukemia 629 Hodgkin \200\231s lymphoma 630 Non-Hodgkin \200\231s lymphoma 631 Bone marrow failure 632 The myeloproliferative disorders 633 Myeloma 634 Paraproteinemia 635 Amyloidosis 635 Inflammatory markers 636 Hyperviscosity syndromes 636 The spleen and splenectomy 637 Thrombophilia 638 Immunosuppressive drugs 639 5 1 Relevant pages elsewhere: Transfusion (p. 456) 608 Anemia Anemia is defined as a low hemoglobin concentration due a decreased red cell mass. I f the low Hb concentration is due to increased plasma volume, as in pregnancy, the anemia i s then considered physiological. A low hemoglo- bin (Hb) level is <13.5 g/dL for men and <1 1.5 g/dL for women. Anemia may be due to reduced production or increased loss of red blood cells (RBCs) and has many causes. The cause of the anemia will be resolved by synthesis of the history, physical examination, and inspection of the blood smear. Symptoms Fatigue, dys pnea, palpitations, headache, tinnitus, anorexia, dyspepsia, bowel disturbance and angina i f there is preexisting coronary artery disease. Patients who have developed their anemia ra pidly are often more symptomatic than those who have developed anemia slowly, in which case there has been time for physiologic compensations for their anemia to occur. Signs Pal lor (evident in conjunctivae) and retinal hemorrhages. In severe anemia (Hb <8 g/dL), there may be signs of a hyperdynamic circulation, with tachycardia, a systolic ejection murmur, and cardiac enlargement. Later, heart failure may occur and, in this state, rapid blood tra nsfusion may be fatal. Types of anemia The first step in diagnosis is to look at the mean c ell volume (MCV, normal MCV is 80 \200\223100 fL ) and the red cell distribution width (RDW , a measure of the variability of the red cell size). Low MCV (microcytic): \212 \212 \212 \212 NB: Anemia of inflammation is distinguished from iron deficiency by iron studies : Serum iron, transferrin, and transferrin saturation will be reduced whereas ferritin will be normal or elevated. Both the anemia of inflamma- tion and some thalassemias tend to hav e near normal RDWs. Normal MCV (normocytic anemia) y g o o t a m e H l Iron-deficiency anemia (IDA, most common cause; Anemia of inflammation Thalassemia Siderobl astic anemia p. 609) \212 \212 \212 Anemia of chronic disease Bone marrow failure Chronic Kidney Disease \212 \212 \212 Hypothyroidism (or Hemolysis (or \206\221 MCV) Pregnancy \206\221 MCV) High MCV (macrocytic anemia) B \212 12 or folate deficiency \212 \212 \212 \212 \212 \212 \212 \212 \212 Myelodysplastic syndromes Marrow infiltration Hypothyroidism Antifolate drugs Bone marrow f ailure states Alcohol Liver disease Reticulocytosis Cytotoxics, e.g., hydroxyurea Hemolytic anemias: Do not fall neatly into the above classification as the anemia may be no rmochromic, or, if the reticulocyte percentage is very high, macrocytic. Suspect a hemolyti c anemia if there is a reticulocyto- sis (>2% of RBCs; or reticulocyte count >85 \227 10 9 /L), mild macrocytosis, haptoglobin \206\223 (p. 616), bilirubin \206\221 , and urobilin ogen \206\221 . If the RDW is very elevated (>20), consider a microangiopathic process suc h as disseminated intravascular coagulation (DIC) or thrombotic thrombocytopenic purpura (T TP). Blood transfusion Avoid unless Hb has fallen acutely and the patient is symptomatic. T ransfusion decisions will depend on the severity, the cause, and the underlying medical sta tus of the patient. If risk of hemorrhage (e.g., active peptic ulcer), transfuse up to 8 g/ dL. In severe anemia with heart fail- ure, transfusion is vital to restore Hb to safe level s: e.g., 8 \200\22310/dL, but must be done with great care. Give packed cells slowly with 1 0 \200\22340 mg furosemide IV/PO with alternate units (dose depends on previous exposure to diuret- ics). Check for rising jugular venous pressure (JVP) and basal crackles. 609 Iron-deficiency anemia Iron deficiency is common (seen in up to 14% of menstruating women) and, worldwide, is the most frequent cause of nutritional anemias. The most common cause is blood loss, particularly menorrhagia or GI bleeding from esophagitis, peptic ulcer, carcin oma, colitis, or diverticulitis. In the tropics, hookworm (GI blood loss) is the most common cause. Poor diet may cause iron-deficiency anem ia (IDA) in infants and children, those on special diets, strict vegetarians, or wherever t here is poverty. Iron deficiency anemia due to malabsorption (gastric surgery, gastric bypa ss, celiac disease, Whipple \200\231s disease, inflammatory bowel disease) may be accompani ed by other defi- ciency states, such as of folate and B 12 . See Table 15.1. Symptoms: Ass ociated symptoms include ice craving (pagophagia), restless leg syndrome, and short-term me mory loss (adolescents). Signs: Koilonychia (p. 43), atrophic glossitis, and, rarely, postc ricoid webs. Investigations: Microcytic, hypochromic blood movie showing anisocytosis and p oikilocytosis (p. 612). Confirmed by showing serum iron \206\223 and ferritin \206\223 (m ore representative of total body iron) with TIBC \206\221 . If MCV \206\223 , and there i s a good history of menorrhagia, oral iron may be started without further tests. Otherwise investigate: Fecal occult blood, barium enema or colonos- copy, gastroscopy, microscope sto ol for ova. Iron deficiency without an obvi- ous source of bleeding mandates a careful gi w orkup . Treatment: If the MCV is low and there is a history of menorrhagia, oral iron may b e started without further diagnostic workup: Oral iron salts (e.g., ferrous sulfate 324 mg bid or tid PO). Side effects (Se) : Constipation, black stools. Hb should rise by 1 g/dL/wk , with a modest reticulocytosis (i.e., young RBC [p. 612]). Continue until Hb is normal and for at least 3 months to replenish stores. Parenteral iron is reserved for patients who fa il oral iron trials or dialysis patients and is available as iron gluconate, sucrose, or fe rumoxytol (well tolerated) or iron dextran (higher side-effect profile). Refractory anemia The usual reason that IDA fails to respond to iron replacement is failure of compliance, of ten because of GI disturbance. Altering the dose of elemental iron or the formulation of el emental iron may be helpful, or considere IV iron in appropriate situations. Other rea- son s for failure of oral iron supplementation include continued blood loss or malabsorption. I mportantly, anemia of inflammation or thalassanemia will not respond to iron supplementatio n. The anemia of chronic disease This is associated with many diseases, including infection, c ollagen vascu- lar disease, rheumatoid arthritis, malignancy, and chronic kidney disease. I nvestigations: Mild normocytic anemia (e.g., Hb >8 g/dL), TIBC \206\223 serum iron \206 \223 , ferritin normal or \206\221 . Treatment: Treat the underlying disease. The anemia o f chronic kidney disease is partly due to erythropoietin deficiency, and recombinant erythr opoietin is effective in raising the hemoglobin level (maintenance dose example: 50 \200 \223150 U/kg twice weekly; se : Hypertension in patients with chronic kidney disease). It i s also effective in raising HB and improving quality of life in those with HIV-related anem ia, chemotherapy induced-anemia, chronic bone marrow failure states, and the anemia of many chronic inflammatory states. 610 Sideroblastic anemia Characterized by dyserythropoiesis and iron loading (bone marrow) and sometimes hemosiderosis (endocrine, liver, and cardiac damage), sidero- blastic anemia (SA) may be congenital (rare, X-linked) or acquired (usually idiopathic, part of the spectrum o f the myelodysplastic disorders), but may follow alcohol or lead excess, myeloproliferative disease, malignancy, mal- absorption, or anti-tuberculosis (TB) drugs. Stippled, hypochrom ic RBCs are seen on the blood movie with sideroblasts in the marrow (erythroid pre- cursors with iron deposited in mitochondria in a ring around the nucleus). y g o o t a m e H Table 15.1 Interpretation of iron studies l Iron \206\223 \206\223 \206\221 \206\221 \206\221 \206\221 tibc \206\221 \206\223 \206\223 \206\223 (or \206\224 ) \206\221 \206\224