578 outside the United States). Nearly all cases in the United States are from bat bites (bewar e of any exposure; bat bites may be unapparent); nearly all in developing world are dog bit es. Incubation is usually 9 \200\22390 d, so give prophylaxis even several months after exp osure. Prodrome symptoms include headache, malaise, abnormal behavior, agitation, fever, an d itching at the site of the bite. Disease progresses to \200\234furious rabies \200\235; e.g., with water provoking muscle spasms and may be accompanied by profound terror (hydroph obia). In 20%, \200\234dumb rabies \200\235 starts with flaccid paralysis in the bitten li mb and spreads. Treatment if bitten where rabies is endemic (if unvaccinated): Seek expert help. If bite is from a domestic dog, cat, or ferret, the animal can be ob- served for 10 d . If bite is from skunk, raccoon, fox, or bat, the animal can be euthanized and tested. If this is not possible, give postexposure prophylaxis (previously not vaccinated); wound clea nsing, human rabies immune globu- lin (HRIG) 20 IU/kg, give as much as possible into wound, give rest IM + vaccine (HDCV or PCECV)1.0 m L IM (not HRIG site) on days 0,3,7,14. For tho se previously vaccinated, give IM vaccine at day 0 and 3 and no HRIG. Pre-exposure prophyla xis (e.g., veterinarians, zoo-keepers, customs officials, bat handlers, and certain travele rs): Give three doses of vaccine IM (days 0, 7, 21 \200\22328). Rabies is usually fatal onc e symptoms begin, but survival has been docu- mented in a handful of patients. A neuroprote ctive protocol is available through Children \200\231s Hospital of Wisconsin. s e s a e s i d s u o i t c e f n I Miscellaneous gram-positive bacteria Staphylococci When pathogenic, these are usually eithe r S. aureus or co- agulase - negative Staphylococci (CONS). Typically, S. aureus cause loca lized infection of skin, lids, or wounds, as well as invasive bloodstream and deep tissue i nfections. Severe infections with S. aureus include pneumonia, osteo- myelitis, septic arth ritis, endocarditis, and septicemia. S. aureus toxins may cause food poisoning (or the toxi c shock syndrome toxin [TSST \200\2231]). The latter presents as shock, confusion, fever, r ash with desquamation of digits, diarrhea, myalgias, CPK elevation, and thrombocytopenia an d is associated with colonization or infection by toxin-producing staphylococci. CONS are t he most common cause of bloodstream infections in hospitalized pa- tients and important cau ses of medical device-associated infections. When isolated from a culture, CONS are frequen tly contaminants. Up to 80% of CONS in blood cultures are contaminants. Clues to actual inf ection are recovery from a normally sterile site in the appropriate clinical context. Methi cillin-resistant S. aureus (MRSA) is a major issue in health care system- acquired and comm unity-acquired infection, causing pneumonia, septicemia, wound infections, and deaths. In t he United States, about 50% of nosocomi- al S. aureus infections are MRSA. Management of he alth care system MRSA: The usual drug is vancomycin; more recently, linezolid and daptomyci n have been introduced. All three are essentially universally active against MRSA. However, daptomycin should not be used in cases of pneumonia as it is inactivated by surfactant. Co mmunity-acquired MRSA (USA 300 strain) has emerged as an important cause of skin and soft-t issue infection. Such staph- ylococcal infections are due to strains that are clonal, globa l, and harbor genes for the Panton-Valentine leukocidin that is associated with virulence. These strains usually harbor the mec IV element that confers resistance to \222 -lactams. Sensitivity tests usually show susceptibility to clindamycin, doxy- cycline, gentamicin, an d TMP/SMX. The most common infections are large furuncles that require surgical drainage. O ther less common infections are necrotizing fasciitis, necrotizing pneumonia, and pyomyosit is. Management: Simple cutaneous abscess require drainage, and antibiotics are optional. 579 Antibiotics should be used in cases of systemic illness; cellulitis; rapid pro- gression; d eeper or extensive infection;, hand, face, or genital involvement; and in patients with imm unosuppression, significant comorbid illness, septic phlebitis, and the elderly. If used, t he usual recommendation is TMP/SMX or doxycycline, clindamycin, or linezolid (much more exp ensive). For patients requiring hospitalization vancomycin, linezolid, and daptomycin (exce pt in lung) can be used. Ceftaroline and telavancin can be considered in skin and soft-tiss ue infections. Preventive measures: Isolate recently admitted patients with suspected MRSA. Group MRSA patients together or place in single isolation rooms. Cleanse hands (alcohol ge l is good) and use gloves and gowns in patient rooms. Use dedicated stethoscope or cleanse it after con- tact. Ask about the need for eradication (with mupirocin). Be meticulous in l ooking after intravascular catheters. Perform surveillance swabs of patients and possibly s taff during outbreaks. Masks may be needed during contact with MRSA pneumonia. Management o f recurrent MRSA skin infection: Cover draining wounds to reduce spread; maintain good pers onal hygiene; cleanse towels, linens, and clothes that have come in contact with MRSA wound ; trim long fingernails because under surfaces may be sites of colonization. Cleanse high-t ouch surfaces in the home. Consider personal decolonization with mupirocin twice daily to a nterior nares for 5 \200\22310 d and skin antiseptic (e.g., chlorhexidine) for 5 \200\22314 d. Streptococci Group A streptococci (e.g., S. pyogenes ) are common pathogens, causing wo und and skin infections (e.g., impetigo, erysipelas), tonsillitis, scarlet fever, necrotizi ng fasciitis, toxic shock, or septicemia. Late complications are rheumatic fever and postst reptococcal glomerulo- nephritis. S. pneumoniae ( Pneumococcus, gram-positive diplococcus) causes pneumonia, otitis media, meningitis, septicemia, and peritonitis (rare). Resistance to penicillin is a problem. S. sanguis, S. mutans , and S. mitis (of the \200\234viridans \200\235 group), S. bovis , and Enterococcus faecalis all cause SBE. E. faecalis also cause s UTI, wound infections, and septicemia. S. mutans is a very common cause of dental caries. S. milleri forms abscesses (e.g., in CNS, lungs, and liver). Most streptococci are sensiti ve to the penicillins, but E. faecalis and E. faecium may present some difficulties. They u sually respond to a combination of ampicillin and an aminoglycoside (e.g., gentamicin). Van comycin-resistant enterococci (VRE) are generally sensitive to linezolid and daptomycin, al though resistance is emerging. Anthrax ( Bacillus anthracis ): Occurs in Africa, Asia, Chin a, Eastern Europe, and Haiti. Spread by handling infected carcasses; well-cooked meat poses no risk. In 2001, anthrax was used as a biological weapon. Presentation: Common form: Loca l cutaneous \200\234malignant pustule. \200\235 Edema may be a striking sign fever and hepatosplenomegaly. Anthrax may cause pulmonary or GI anthrax with breathlessness or massiv e GI hemorrhage ( meningoencephalitis). Tests: CXR may show a widened mediastinum and ple ural effusion. Infiltrates are rare. Gram stain is sometimes diagnostic (gram-positive rod) . Treatment: Cutaneous disease: Ciprofloxacin 500 mg/12 h PO or doxycycline 100 mg bid for 60 d. Pulmonary or GI anthrax: Ciprofloxacin 400 mg/12 h or doxycycline 100 mg bid IV with clindamycin 900 mg/8 h IV + rifampicin 300 mg/12 h IV or imipenem 1 g IV q6h. Switch to ora l drugs when able; adjust based on susceptibility and treat for 60 d. Prevention: Immunizat ion of animals at risk and enforcement of sound food- handling and carcass-hygiene policies . A human vaccine (AVA) is indicated for very specific groups. In bioterrorism, doxycycline or ciprofloxacin is highly effective in preventing disease among those exposed. There is a lso a role for postexposure vaccination with AVA. The mortality for pneumonia treated with ciprofloxacin and other agents is 40 \200\22350%. Bloody pleural effusions must be drained. 580 Diphtheria is caused by the toxin of Corynebacterium diphtheriae . Presents with tonsilliti s a pseudomembrane over the throat and lymphadenopathy ( \200\234bull neck \200\235). Di phtheria is extremely rare in the United States, but endemic in multiple developing countri es and states of the former Soviet Union. Complications include airway obstruction, myocard itis, and polyneuropathies. Treatment: Equine diphtheria antitoxin (EDA) and erythromycin o r penicillin is used to eradicate the organism. EDA can be obtained from CDC (770 \200\2234 88 \200\2237100). Prevention: Diphtheria toxoid vaccine (as part of combination with tetanu s pertussis vaccines). Give all close contacts prophylaxis with erythromycin or penicill in. Listeriosis is caused by Listeria monocytogenes , a gram-positive bacillus with an unus ual ability to multiply at low temperatures. Possible sources of infection include p t s, raw vegetables, unpasteurized milk, and soft cheeses (brie, camembert, and blue-vein t ypes). It may cause a nonspecific flu-like illness, pneumonia, meningoencephalitis, ataxia, rash, or FUO, especially in the immunocompromised; in pregnancy, where it may cause miscar riage or stillbirth; and in neonates. Diagnosis: Culture blood, placenta, amniotic fluid, C SF, and any expelled products of conception. Take blood cultures in any pregnant patient wi th unexplained fever for 48 h. Serology, vaginal, and rectal swabs don \200\231t help (it m ay be a commensal here). Treatment: Ampicillin IV (TMP/SMX if allergic) gentamicin. Prev ention in pregnancy: Avoid soft cheeses, p t s, and undercooked meat. Observe \200 \234use by \200\235 dates. Ensure reheated food is piping hot; observe standing times when using microwaves; throw away any leftovers. Nocardia species In the United States, nocardio sis is typically a disease of immunocompromised patients (e.g., steroids, transplant, advan ced HIV), where it can cause pulmonary, liver, and brain abscesses. Microscopy: Branching g ram-positive chains. Treatment: TMP/SMX amikacin is the mainstay of therapy. Imipenem, m inocycline are alternatives. Check susceptibilities. In warm climates, Nocardia can cause s ubcutaneous infection (e.g., Madura foot). Clostridia ( C. perfringens ) causes wound infec tions and gas gangrene shock or renal failure after surgery or trauma. Treatment: Debrid ement is essential; penicillin 1.2 \200\2232.4 g/6 h IV + clindamycin 900 mg/8 h IV, antito xin, and hyperbaric oxygen may also be used. Amputation may be necessary. Clostridia food p oisoning: See section on GI illness. C. dif \201 cile: Diarrhea (the cause of pseudomembra nous colitis following antibiotic therapy). This has emerged as a major problem in hospital ized patients. Keys to management include discontinuation of offending antibiotics whenever feasible, metronidazole, or vancomycin. Fidaxomicin is newly approved for C. difficile col itis and may be associated with fewer recurrences. C. botulinum (botulism): C. botulinum to xin blocks release of acetylcholine causing descending flaccid paralysis. Botulism is not s pread from one person to another. There are two adult forms of botulism: Food-borne and wou nd botulism, which is a problem in IV drug abusers if heroin is contaminated with C. botuli num . Signs: Afebrile, flaccid paralysis, dysarthria, dysphagia, diplopia, ptosis, weakness , respiratory failure. Autonomic signs: Dry mouth, fixed or dilated pupils. Tests: Find tox in in blood samples or, in the case of wound botulism, by the identification of C. botulinu m in wound specimens. Samples include serum, wound pus, swabs in anaerobic transportation m edia. Management: Get help and transfer to ICU. Botulinum antitoxin works if given early. B efore giving antitoxin, skin testing is required to evaluate for sensitivity to serum or an titoxin. Then give one vial of IV antitoxin. Also consider in those who have ingested toxin but who have not yet developed symptoms. C. botulinum is sensitive to penicillin and metro nidazole. If suspecting a case of botulism, contact local state health department for assis tance. If not available, contact CDC at (770) 488 \200\2237100. s e s a e s i d s u o i t c e f n I 581 Actinomycosis is usually caused by Actinomyces israelii . Presentations include subcutaneou s infections, forming chronic sinuses with sulfur granule-containing pus. It commonly affec ts the area of the jaw. It may cause abdominal masses (may mimic appendix mass). Treatment: Penicillin for many months. Consult with surgeons. Miscellaneous gram-negative bacteria Enterobacteriaceae Some are normal gut commensals, oth ers environ- mental organisms. They are the most common cause of UTI and intra-ab- dominal sepsis, especially postoperatively and in the acute abdomen. They are also a common cause o f septicemia due to nosocomial pneumonia and catheter-associated infection. Enterobacteriac eae are a rare cause of meningitis or endocarditis but may cause these infections when ther e are indwelling devices (e.g., prosthetic valves, ventricular drains). These organ- isms a re often sensitive to ampicillin and TMP/SMX, but in serious infec- tions, use cefuroxime o r third- or fourth-generation cephalosporin, quino- lones, or carbapenems an aminoglycos ide. Pseudomonas aeruginosa is a serious pathogen, especially in the immunocompromised and in patients with cystic fibrosis. It causes pneumonia, septicemia, UTI, wound infection, os teomyelitis, and cutaneous infections. The main problem is its tendency to be resistant to many antibiotics. Treatment: Piperacillin/tazobactam, cefepime, ceftazidime, aztreonam, mer openem, imipenem, or doripenem. If using aminoglycosides (e.g., amikacin, gentamicin, tobra mycin) or colistin, these should not be used alone. Ciprofloxacin and other quinolones are the only oral anti- Pseudomonas antibiotics. Acinetobacter baumannii has recently emerged a s a major cause of health care system- and traumatic injury- associated infection. A. bauma nnii causes skin, soft-tissue, and bone infec- tions in soldiers injured in Iraq and Afghan istan, as well as postoperative, bloodstream, and lung infection in hospitalized patients. These organisms are often resistant to multiple classes of antibiotics. Multi-drug resistan t Acinetobacter, Enterobacteriaceae, and pseudomonal infections are an increasingly importa nt problem in hospitalized patients and, in some cases, therapeutic options are extremely l imited. Haemophilus influenzae type B typically affects unvaccinated children usually <4 yr s old. It causes otitis media, acute epiglottitis, pneumonia, meningitis, osteomyelitis, an d septicemia. In adults, nontypeable strains may cause exacerbations of chronic bronchitis, sinusitis, and pneumonia. Treatment: Unreliably sensitive to ampicillin and TMP/SMX; cefot axime, quinolones, azithromycin amox-clavulanate are more reliable. Capsulated types tend t o be much more pathogenic than noncapsulated types. Prevention: Immunization with HIB vacci ne has resulted in a dramatic fall in incidence. Plague is caused by Yersinia pestis . Spre ad: Fleas of rodents or cats, or droplets from other infected humans. Incubation: 1 \200 \2237 d. Bubonic plague presents with lymphadenopathy (buboes). Pneumonic plague may presen t with lymphadenopathy or a flu-like illness leading to dyspnea, cough, copious, bloody spu tum, septicemia, and a hemorrhagic fatal illness. Diagnosis: Phage typing of bacterial cult ure or a fourfold rise in antibodies to F antigen. Treatment: Isolate suspects. Streptomyci n 15 mg/kg/12 h IV or gentamicin 5 mg/kg/d or 2 mg load followed by 1.7 mg/kg/8 h for 10 d. Doxycycline and ciprofloxacin are alternatives. Patients with suspected or confirmed Y. pe stis infection should be maintained in respiratory droplet isolations (gloves, gowns, eye p rotection) until at least 48 h of ABX therapy and clinical improvement. Postexposure prophy laxis: Doxycycline 100 mg/12 h PO for 7 d or ciprofloxacin 500 mg PO bid \227 7 d and moni tor for fever or cough during this time. 582 Brucellosis This zoonosis (carried by domestic animals) is common in multiple countries inc luding those in the Middle East, Mediterranean basin, South and Central America, and Africa . Typically affects vets or farmers, but can be foodborne. Unpasteurized dairy products (e. g., \200\234village cheese \200\235) are a risk to travelers. Cause: B. melitensis (the mo st virulent), B. abortus, B. suis , or B. canis . Symptoms may be indolent and last for yea rs with fever, sweats, malaise, anorexia, vomiting, weight loss, hepatosplenomegaly, consti pation, diarrhea, myalgias, backache, arthritis, sacroiliitis, rash, bursitis, orchitis, an d depression. Complications: Osteomyelitis, SBE (culture negative), abscesses (liver, splee n, lung), meningoencephalitis. Diagnosis: Blood culture (may take many days to grow), serol ogy: If titers equivocal (e.g., >1:40 in nonendemic zones) do ELISA immunoradiometric as says; pancytopenia is a clue. Notify laboratory if Brucella is a possibility; it is a labor atory hazard. Treatment: Doxycycline + rifampin \227 6 wks, or doxycycline for 6 wks + str eptomycin ( \227 2 \200\2233 wks) or gentamicin ( \227 1 week); some recommend doxycyclin e + rifampin \227 6 wks + gentamicin \227 2 wks. Whooping cough is caused by Bordetella p ertussis . Presentation: This begins with a prodromal catarrhal phase with fever and cough. After a week or so, the patient develops paroxysms of coughing. There may be the character istic inspiratory whoops, but this is not always present in adults. Most patients recover w ithout complication, although the cough may last some months. Some, especially the very you ng, may develop pneumonia (and consequent bronchiectasis) or convulsions and brain damage. Prevention efforts include vaccinating adults with DTaP in place of Td. Diagnosis: Nasophar yngeal aspirate or Dacron swab culture or PCR. Treatment: A macrolide given early in the co urse can decrease the duration, severity, and communicability of pertussis. Treatment is wi th azithromycin 500 mg/d \227 1, then 250 mg/d \227 4 d, clarithromycin 500 mg/12 h \227 7 d, erythromycin 500 mg/6 h \227 14 d, and TMP/SMX DS/12 h \227 14 d. Administer postex posure prophylaxis with the above courses of antibiotics to close contacts. Pasteurella mul tocida is acquired via domestic animals, especially cat or dog bites. Presentation: It can cause cutaneous infections, septicemia, pneumonia, UTI, or meningitis. Treatment: Susceptib le to PCN, but best to treat with amoxicillin/clavulanate or ampicillin/sulbactam to cover potential co-pathogens from animal oral flora. Yersinia enterocolitica In Scandinavia, this is a common cause of a reactive, asymmetrical polyarthritis of the weight-bearing joints, and, in America, of enteritis. It also causes uveitis, appendicitis, mesenteric lymphadenit is, pyomyositis, glomerulonephritis, thyroiditis, colonic dilatation, terminal ileitis and perforation, and septicemia. Diagnosis: Serology is often more helpful than culture, as the re may be quite a time lag between infection and the clinical manifestations. Agglutination titers of >1:160 indicate recent infection. Treatment: None may be needed, or ciprofloxaci n 500 mg/12 h PO for 3 \200\2235 d, TMP/SMX, gentamicin, and third-generation cephalosporin are usually effective. Moraxella catarrhalis (gram-negative diplococcus) is a rare cause o f pneumonia and occasional cause of exacerbations of COPD, otitis media, sinusitis, and sep ticemia. Treatment: Clarithromycin 500 mg/12 h PO. Azithromycin, doxycycline, amoxicillin-c lavulanate, and quinolones are effective. Tularemia is caused by Francisella tularensis (gr am-negative bacillus), which may be acquired by multiple routes (tick bites, contact with i nfected animal carcasses, inhalation of contaminated dust or aerosol, ingestion of contamin ated water). It causes rash, fever, malaise, tonsillitis, headache, hepatosplenomegaly, and lymphadenopathy. There may be papules at sites of inoculation (e.g., fingers). It has the potential for use as a bioweapon. Complications: Meningitis, osteomyelitis, SBE, pericardit is, septicemia. s e s a e s i d s u o i t c e f n I 583 Diagnosis: Contact local microbiologist for advice. Only use laboratories with safety cabin ets suitable for dangerous pathogens. Swabs and aspirates must be transported in approved c ontainers. Treatment: Gentamicin 1 \200\2231.7 mg/kg/8 h or streptomycin 7.5 \200\22310 mg/ kg/12 h IM for 2 wks. Oral tetracycline or ciprofloxacin are suitable for chemoprophylaxis. Prevention: Find the animal vector; reduce human contact with it as much as possible. Vacc ination may be possible for high-risk groups. Cat scratch disease Mostly due to Bartonella henselae (a small, curved, pleomorphic, gram-negative rod) or Afipia felis . Think of this with an inoculating cat scratch + regional lymphadenopathy + negative evaluation for other causes of lymphadenopathy; establish diagnosis with Warthin- Starry stain of biopsy or sero logy; skin lesions may resemble Kaposi \200\231s sarcoma. Treatment: Usually resolves spont aneously within 1 \200\2232 months. One trial found that azithromycin hastened resolution o f lymph nodes. Other drugs that have been used include ciprofloxacin, rifampin, and TMP/ SM X. Tetanus Toxin of Clostridium tetani produces the exotoxin tetanospasmin, which causes muscl e spasms and rigidity, the cardinal features of tetanus ( \200\234to stretch \200\235). Inc idence 30 cases per year in the United States. Mortality is about 10 \200\22320%. Pathoge nesis Spores of C. tetani live in feces, soil, dust, and on instruments. A tiny breach in s kin or mucosa (e.g., cuts, burns, ear piercing, banding of hemorrhoids) may allow entry of the spores. (Diabetics are at increased risk.) Spores may then germinate and make the exoto xin. This then travels up peripheral nerves and interferes with inhibitory synapses. The pa tient 15 \200\22325% will have no evidence of recent wounds . Signs appear from 1 day to se veral months from the (often forgotten) injury. There is a prodrome of fever, malaise, and headache before classical features develop: Trismus (lockjaw; difficulty in opening the mou th); risus sardonicus (a grin- like posture of hypertonic facial muscles); opisthotonus (ar ched body with hyperextended neck); spasms (which at first may be induced by movement, inje ctions, noise, etc., but later are spontaneous; they may cause dysphagia and respiratory ar rest); autonomic dysfunction (arrhythmias and wide fluctuations in BP). Differential diagno sis includes dental abscess, rabies, phenothiazine toxicity, and strychnine poisoning. Phen othiazine toxicity typically affects facial and tongue muscles. Poor prognostic signs are s hort incubation, rapid progression from trismus to spasms (<48 h), development postpartum o r postinfection, and tetanus in neonates and old age. Treatment Get expert help; use ICU, m onitor electrocardiogram (ECG) + blood pressure (BP), and monitor fluid balance. Clean/debr ide wounds, IV metronidazole 500 mg/6 h for 7 \200\22314 d is preferred; can also use PCN. If tetanus is established, give human tetanus immune globulin (HTIG) 500 units IM or IV (WH O recommendation) or 3,000 \200\2235,000 units IM (CDC) to neutralize free toxin. Some advo cate intrathecal administration of antitoxin. Early ventilation and sedation if symptoms pr ogress. Control spasms: Diazepam 0.05 \200\2230.2 mg/kg/h IV or phenobarbital 1.0 mg/kg/h I M or IV + chlorpromazine 0.5 mg/kg/6 h IM (IV bolus is dangerous) starting 3 h after the ph enobarbital. If this fails to control the spasms, paralyze and ventilate (get anesthetist \200\231s help). 584 Postinjury prophylaxis T d or T dap: Any cut merits an extra dose of tetanus toxoid IM, unl ess history of three or more toxoids or a booster in last 10 yrs (5 yrs for more severe wou nds). Human tetanus immunoglobulin: This is required for those with fewer than three toxoid boosters in past and with dirty, old (>6 h), infected, devitalized, or soil-contaminated w ounds. Give 250 \200\223500 units IM, using a separate syringe and site to the toxoid injec tion. If immune status is unknown, assume that the patient is nonimmune. Routine infant imm unization started in 1961, so many adults are at risk. Hygiene education and wound debridem ent are of vital importance. s e s a e s i d s u o i t c e f n I Enteric fever Typhoid and paratyphoid are caused by Salmonella typhi and S. paratyphi (type s A, B, and C), respectively. (Other Salmonella species cause diar- rhea and vomiting.) Inc ubation: 3 \200\22321 d. Spread: Fecal \200\223oral. 1% can become chronic carriers. Presen tation: Usually malaise, headache, high fever with rel- ative bradycardia, cough, and const ipation (or diarrhea). CNS signs (coma, delirium, meningitis) are serious. Diarrhea is more common after the first week. Rose spots occur on the trunk of 40%, but may be very difficu lt to see. Epistaxis, bruising, abdominal pain, and splenomegaly may occur. Tests: First 10 d: Blood culture. Later: Urine/stool cultures. Bone marrow culture has highest yield (infi ltration may cause decreased platelets and WBC). LFT can be elevated. Widal test is unrelia ble. DNA probes and PCR tests have been developed, but are not widely available. Treatment: Fluid replacement and good nutrition. There is good evidence that quinolones (e.g., cipro- floxacin 500 mg/12 h PO for 6 d) are the best antimicrobial treatment for typhoid. Chloram phenicol is still used in many areas, but generally avoided in the United States because of myelotoxicity. Other alternatives: Amoxicillin (if fully susceptible), cefixime, and azith romycin. In severe disease, give IV ciprofloxacin, cefotaxime, or ceftriaxone for 10 \200 \22314 d. In encephalopathy shock, give dexamethasone 3 mg/kg IV stat, then 1 mg/kg/6 h for 48 h. Drug resistance is a problem, even with ciprofloxacin; e.g., due to mutations in the DNA gyrase enzyme of S. typhi . Complications: Osteomyelitis (e.g., in sickle-cell dise ase); DVT; GI bleed or perforation; cholecystitis; myocarditis; pyelonephritis; meningitis; abscess. Chronic carriage occurs in 1 \200\2235% of pa- tients. Treat if at risk of spread ing disease (e.g., food handlers). Amoxicillin 4 \200\2236 g/d + probenecid 2 g/d for 6 wks may work ( alternative: Ciprofloxacin 500 mg/12 h PO for 6 wks), but cholecystectomy may b e needed, particu- larly in those with cholelithiasis. Bacillary dysentery Shigella causes abdominal pain and bloody diarrhea sudden fever, hea d- ache, and occasionally neck stiffness. CSF is sterile. Dysentery may be se- vere (often S. flexneri or S. dysenteriae ). Incubation: 1 \200\2237 d. Spread: Fecal \200\223oral. Dia gnosis: Stool culture. Treatment: TMP/SMX DS/12 h, ciprofloxacin 500 mg/12 h, azithromycin 500 mg/d \227 3 \200\2235 d (or longer in immunocompromised patients). Imported shigellosi s is often resistant to several antimicrobials: Sensitivity testing is important. There may be associated spondyloarthritis. 585 Cholera Vibrio cholerae (gram-negative comma-shaped rod): Pandemics or epidemics may occur; e.g., 1990s epidemic in South America and Bangladesh (Bengal Vibrio cholerae 0139 ). Incub ation: Ranges from a few hours to 5 d. Spread: Fecal \200\223oral. Presentation: Profuse (e .g., 1 L/h) watery ( \200\234rice water \200\235) stools, fever, vomiting, and rapid dehydr ation (the cause of death). Diagnosis: Stool microscopy and culture. Treatment: Strict barrier nursing. Replace fluid and salt losses me ticulously. A single dose of ciprofloxacin 1 g PO may reduce fluid loss. Doxycycline, eryth romycin, and TMP/SMX are also effective. Pre- vention: Only drink boiled or treated water. Cook all food well; eat it hot. Avoid shellfish. Peel all vegetables. Heat-killed vaccine ( serovar O1) gives limited protection and is no longer needed for international travel; newe r vaccines are nonstandard. Hansen \200\231s disease (leprosy) It is a chronic infection due to Mycobacterium leprae pr edominantly involving skin, mucosa and peripheral nerves. Historically, victims have been o stra- cized, and this may still be a barrier to self-reporting and early treatment. Conside r avoiding use of term \200\234leprosy \200\235 due to stigma. Hansen \200\231s disease is rare in the United States (150 \200\223250 cases/year). Cases can be imported (e.g., immig rants from endemic countries) or locally acquired in Florida, Texas, Louisiana, and Califor nia. Armadillos may be a source of infection in the Southern United States. Worldwide, ther e are 250,000 new cases/year. Most are from Asia and Africa. Clinical presentation The in cubation period is months to years, and the subsequent course depends on the patient \200 \231s immune response. 95% of the world \200\231s population is not susceptible to infectio n. If the immune response is ineffective, lepromatous or multibacillary (WHO classification ) disease develops, dominated by foamy histiocytes full of bacilli, but few lymphocytes. If there is a vigorous immune response, the disease is called tuberculoid or paucibacillary ( WHO classification), with granulomata containing epithelioid cells and lymphocytes, but few or no demonstrable bacilli. Between these poles lie those with borderline disease. Skin le sions Hypopigmented anesthetic macules, papules, or annular le- sions (with raised erythema tous rims). Erythema nodosum occurs in \200\234lep- romatous \200\235 disease, especially during the first year of treatment. Nerve lesions Major peripheral nerves may be involved, leading to much disability. Sometimes a thickened sensory nerve may be felt running into th e skin lesion (e.g., ulnar nerve above the elbow, median nerve at the wrist, or the great a uricular nerve running up behind the ear). Eye lesions Refer promptly to an ophthalmologist . The lower temperature of the anterior chamber favors corneal invasion (so secondary infec tion and cataract). In \202 ammatory signs: Chronic iritis, scleritis, and episcleritis. T here may be reduced corneal sensation (V nerve palsy), reduced blinking (VII nerve palsy), lagophthalmos (difficulty in closing the eyes), ingrowing eyelashes (trichiasis). Diagno sis Biopsy a thickened nerve; in vitro culture is not possible. Split skin smears for AFB a re positive in borderline or lepromatous disease. Classification matters as it reflects the biomass of bacilli, influencing treatment: The more organisms, the greater the chance that some will be drug resistant. Other tests: Neutrophilia, ESR elevation, IgG elevation. Trea tment It is useful to check with a local expert about resistance patterns (e.g., to dapsone ). Treatment for limited disease (tuberculoid, borderline tuberculoid- paucibacillary using WHO classification) is with dapsone 100 mg/d and rifampin 600 mg/d \227 12 months. In wid espread disease (lepromatous, borderline lepromatous, mid borderline-multibacillary using W HO classification) treat patient with dapsone 100 mg/d + rifampin 600 mg/d + clofazimine 50 mg/d \227 24 months. Clofazimine is obtained from National Hansen \200\231s Disease Progr am: 800 \200\223642 \200\2232477). Minocycline and clarithromycin are also active and may b e used in place of dapsone or clofazimine. Ofloxacin can also be used instead of clofazimin e. Single lesion 586 skin paucibacillary disease is treated with a rifampin 600 mg, ofloxacin 400 mg, and minocy cline 100 mg as a one-time treatment. Beware of inflammatory reactions with therapy caused by infection and/or dying bacilli. Erythema nodosum leprosum , which may present as sudden nerve inflammation ( orchitis, lymphadenitis, nephritis, periostitis, irido- cyclitis) ma y be seen with treatment of widespread infection. Treat with steroids and referral to ophth almologist for ocular disease. Thalidomide or clofazimine may be useful. The latter causes skin pigmentation. Edema and erythema of preexisting lesions (reversal reactions) may even cause skin ulceration and neuritis. Treat with corticosteroids. Neuritis can occur in the a bsence of a reactive episode and may respond to steroids. s e s a e s i d s u o i t c e f n I Spirochetes Lyme disease is a tick-borne infection caused by Borrelia burgdorferi . Al- tho ugh originally described in Lyme (Connecticut) it is now widespread. Not all will remember being bitten by a tick. Presentation: Erythema migrans malaise, cognitive impairment, ly mphadenopathy, arthralgias, myocarditis, heart block, meningitis, ataxia, amnesia, cranial nerve palsies (Bell \200\231s pal- sy), neuropathy, lymphocytic meningoradiculitis (Bannwar th \200\231s syndrome). Diagnosis: If erythema migrans is present at evaluation, then serol ogy is not needed. Otherwise, diagnose using clinical features + serology at 4 \200\2236 wk s. Serology is a two-step process with a screening ELISA followed by confirmatory IgG and I gM immunoblot if ELISA is positive. If symptoms are present >4 months, IgG must be present to be considered positive. Treatment: Skin rash, isolated cranial nerve palsy: Doxycycline 100 mg/12 h PO (amoxicillin, cefuroxime also active) for 14 \200\22321 d, arthritis (21 d). CNS, peripheral nerve disease, carditis, or recurrent arthritis: Ceftriaxone 2 g/d IV (cef otaxime, PCN G also good). Prevention: Keep limbs covered; use insect repellent; tick colla rs for pets; check skin often when in risky areas. Vaccination is no longer available. A si ngle dose of doxycycline 200 mg PO given within 72 h of a bite is effective prophylaxis; in highly endemic areas, this may be worthwhile (e.g., if risk is >1%). Removing ticks: Using fine- tipped tweezers, gently remove tick by grasping it as close to skin surface as possi ble, then pull up with steady, even pressure. Endemic treponematoses Yaws is caused by T. p ertenue , which is serologically indistinguishable from T. pallidum . It is a chronic granu lomatous disease prevalent in children in the rural tropics. Spread is by direct contact, v ia skin abrasions, and is promoted by poor hygiene. The primary lesion (an ulcerating papul e) appears 4 wks after exposure. Scattered secondary lesions then appear (e.g., in moist s kin, but can be anywhere). These may become exuberant. Tertiary lesions are subcutaneous gu mmatous ulcerating granulomata, affecting skin and bone. Cardiovascular and CNS complicatio ns do not occur. Pinta ( T. carateum ) affects only skin; seen in Central and S America. En demic nonvenereal syphilis (bejel ; T. pallidum ) is seen in third-world children, when it resembles yaws. In the developed world, T. pallidum causes syphilis. Diagnosis: Clinical. T reatment: Procaine penicillin. Leptospirosis Caused by bacteria in the genus Leptospira . S pread is by contact with soil or water contaminated by urine or body fluids of infected ani mals (e.g., rodents, livestock, and dogs). Typical exposures involve swimming/rafting/kayak ing in fresh water, especially in tropical regions (e.g., Hawaii, Caribbean) and exposure t o surface water in endemic regions. Presentation: Fever, jaundice, headache, red conjunctiv ae, tender legs (myositis), purpura, hemoptysis, hematemesis, or any bleeding. Meningitis, myocarditis, and renal failure may develop. AST rise may be small. Diagnosis: Rapid serolog ical assays are replacing the old microscopic 587 agglutination test. Also take blood, urine, and CSF culture (for 4 \200\2236 wks). Treat sy mptomatically; give doxycycline 100 mg/12 h or, in serious disease, IV benzylpenicillin 600 mg/6 h for 7 d. Prophylaxis (e.g., doxycycline 200 mg/ wk PO) may be useful for those at h igh risk for short periods. Canicola fever is aseptic meningitis caused by Leptospira canic ola . Relapsing fever Tick-borne relapsing fever (TBRF) is usually caused by Borrelia herms ii. Transmission is via a soft tick. In the United States, most cases are in western mounta inous regions. Louse-borne relapsing fever (LBRF) is caused by B. recurrentis transmitted p erson to person by the body louse. It typically occurs in epidemics following war or disast er. Illness may be severe (30 \200\22370% mortality) with enormous death tolls in outbreak settings. Incubation: 4 \200\22318 d. Presentation: Abrupt onset of fever, rigors, and head ache. A petechial rash (which may be faint or absent), jaundice, and tender hepatosplenomeg aly may develop. Serious complications include myocarditis, hepatic failure, and DIC. Crise s of very high fever and tachycardia occur. When the fever abates, hypotension due to vasod ilatation may occur and be fatal. Relapses occur, but are milder. Tests: Organisms are seen on Leishman-stained thin or thick films. Treatment: TBRF: Erythromycin 500 mg/6 h PO or IV , tetracycline 500 mg/6 h PO or 250 mg/6 h IV, or doxycycline 100 mg/12 h PO or IV \227 7 d. LBRF can be treated with a single dose of ABX. Monitor for Jarisch \200\223Herxheimer re action (fevers chills, hypotension with lysis of organisms) in first few hours after ABX. D elouse the patient and his or her clothes. Doxycycline is useful prophylaxis in high-risk g roups. Viral hemorrhagic fevers Yellow fever An epidemic arbovirus disease spread by Aedes mosquit oes (Brazil, Bolivia, Peru, and Central and West Africa). Incubation: 2 \200\22314 d. Clini - cal presentation: In mild forms, fever, headache, nausea, albuminuria, myal- gias, and re lative bradycardia. If severe: 3 d of headache, myalgias, anorexia nausea, followed by a brupt fever, a brief remission, then prostration, jaundice ( fatty liver), hematemesis an d other bleeding, oliguria. Mortality: <10% (day 5 \200\22310). Diagnosis: ELISA. Treatment : Symptomatic. Lassa fever, Ebola virus, Marburg virus, and dengue hemorrhag- ic fever (DHF ) These diseases may start with sudden-onset headache, pleuritic pain, backache, myalgias, conjunctivitis, prostration, dehydration, facial flushing (dengue), and fever. Bleeding soo n supervenes. There may be spontaneous resolution or renal failure, encephalitis, coma, and death. Treatment: Primarily symptomatic; ribavirin is useful in Lassa fever if given early in disease. Use special infection control measures (Lassa, Ebola, and Marburg); get expert help at once. Dengue is the most prevalent arbovirus disease. There is a global pandemic o f this RNA flavivirus, related to poor vector control ( Aedes mosquitoes), urbanization, an d rapid migrations bringing new strains (DEN \200\2232), which become more virulent in thos e who have had mild dengue. About 50 million cases of dengue infection occur each year and 500,000 are hospitalized each year with DHF. Infants typically have a simple febrile illnes s with a maculopapular rash. Older children/adults have flushing of face, neck, and chest o r a centrifugal maculopapular rash from day 3, or a late confluent petechiae with round pal e areas of normal skin. Also, patients may have headache, arthralgias, jaundice, hepatosple nomegaly, and anuria. Hemorrhagic signs: (Unlikely if AST normal), petechiae, GI, gum or no sebleeds, hematuria, hypermenorrhea. Monitor: BP, urine flow, WBC, HCT, PLT. A positive tou rniquet test (>20 petechiae inch 2 ) + rise in HCT by 20% are telling signs (rapid endothel ial plasma leak is the key pathophysiology of DHF). Differential diagnosis: Chikungunya, me asles, 588