530 with an IV cephalosporin. The major use of cephalosporins is parenteral; e.g., as prophylax is in surgery and in postoperative infection. Suspected life-threatening infections (e.g., severe pneumonia, meningitis, or gram- negative septicemia) may be treated empirically with a third-generation drug. Cephalosporins may also become the drugs of first choice in certa in situations, such as penicillin hypersensitivity (beware of 10% cross- sensitivity) or w here aminoglycosides are better avoided. The main adverse effect of the cephalosporins is h ypersensitivity. This is seen in <10% of penicillin-sensitive patients. There may be GI ups et, reversible changes in liver function tests, eosinophilia, rarely neutropenia, nephrotox icity, and colitis. There are reports of clotting abnormalities, and there may be false-pos itive results for glycosuria or the Coombs \200\231 test. Most broad-spectrum cephalosporin s potentiate warfarin. There are over a dozen cephalosporins on the market. A representativ e sample is presented below: s e s a e s i d s u o i t c e f n I Table 14.7 Cephalosporins Antibiotic (and its uses) Usual adult dose Adjustment for creatinine clearance (mL/min) First-generation cephalosporins Cefazolin: Range of 1 \200\2232 g/6 \200\2238 h IV. Use higher doses with bacteremia 250 \200\223500 mg/6 CrCl 10 \200\22335: 0.5 \200\2231 g/12 h, infections due to MSSA, susceptible streptococci, E. coli and other gram-negative aerobes <10: 0.5 \200\2231 g/24 h HD:0.5 \200\2231 g/24 h + 1 g after HD Cephalexin: Similar in CrCl 10 \200\22330: q8 \200\22312h, <10: spectrum to cefazolin, but in oral formulation h PO q12 \200\22324h HD: Q12 \200\22324h dose after HD Second-generation cephalosporins 0.75 \200\2231.5 g Cefuroxime: Range of infec- tions due to susceptible streptococci and gram- negative aerobe s, esp. respiratory and GU CrCl 10 \200\22350(IV): Q8 \200\22312h, <10 (IV) 0.75 g/24, (PO) 250 mg/24 h HD: Give dose after HD /6 \200\2238 h IV 250 \200\223500 mg/12 h PO 0.5 \200\2233 g/12 h IV Cefotetan: Range of infec- tions due to susceptible gram-negative aerobes, and anaerobes, e sp. GI/GU CrCl 10 \200\22330 1 \200\2232 g/24, <10 1 g/24 \200\22348 h HD: 0.5 \200\2231 g/24 h + 1 g after HD 531 Third-generation cephalosporins Ceftriaxone: Many gram- positive and negative infections. Excellent CNS levels. Not active against Listeria, enterococci, and Pseudomonas 1 \200\2232 g/12 \200\22324 No adjustment h IV Cefixime: Similar in spec- trum to ceftriaxone 400 mg/24 h CrCl 10 \200\22350: 300 mg/d, PO <10: 200 mg/d HD: 300 mg/d, give dose after HD (Continued) Table 14.7 (Continued) Antibiotic (and its uses) Usual adult dose Adjustment for creatinine clearance (mL/min) Advanced-generation cephalosporins Cefepime: Good activ- 1 \200\2232 g/8 h IV CrCl 30 \200\22360: 1 \200\2232 g/12 \200\22324 h, <30:0.5 \200\2232 g/24 h HD: 0.5 \200 \2232 g/24 + 1 g ity against Pseudomonas , Enterobacter , and other resistant gram-negative organisms, and S . aureus . Ceftaroline: Many gram- positive and -negative infec- tions and MRSA; not active against Pseudomonas after HD or dose after HD 600 mg/12 h IV CrCl 30 \200\22350: 400 mg/12 h, 15 \200\22330:300 \200\223400 mg/12 h, <10: 200 \200\22340 0 mg/12 h Aminoglycosides These are broadly active against aerobic gram-negatives and synergistic wit h ampicillin in enterococcal endocarditis. Monitor levels and avoid extended therapy to red uce chance of renal and inner ear toxicities. AGs are dosed once daily or intermittently. O nce daily is not recommended for meningitis and patients with renal dysfunction. In the lat ter, use intermittent dosing, start with standard loading dose, obtain pharmacist assistanc e for further dosing, follow levels closely, and consider nonaminoglycosides options. Try t o avoid use in patients with myasthenia gravis, concomitant nephrotoxic drugs, and pregnanc y. Table 14.8 Aminoglycosides Gentamicin Once daily: 5 \200\2237 mg/kg/24 h. Target trough <1 (mcg/mL) Intermittent: 2 \200\2233 mg/ kg load then 1.7 \200\2232 mg/ kg/8 h. Target Peak >6 \200\2238, trough <2 (mcg/mL) Enteroc occus synergy: 1 mg/kg/8 h, target peak 3 \200\2235 (mcg/mL) Once-daily dosing : 15 \200 \22320 mg/kg/24 h. Target trough <4 (mcg/mL) Intermittent dosing : 8 \200\22312 mg/kg load then 7 \200\2238 mg/kg/8 h or 7.5 \200\22310 mg/kg/12 h. Target peak >20 \200\22335, trough <10 (mcg/mL) Amikacin: resistance organisms gentamicin L ess in some to than 532 Macrolides Active against many community respiratory tract pathogens, travelers \200\231 di arrhea, H. pylori , sexually transmitted infections, nontuberculous mycobacteria. s e s a e s i d s u o i t c e f n I Table 14.9 Macrolides Sinusitis/pharyngitis/otitis media/bronchitis/ pertussis/mild community acquired pneu- moni a (CAP): 500 mg day 1 then 250 mg/d \227 4 d Mild to moderate CAP: 500 mg/d \227 5 \200 \22310 d Moderate to severe CAP: Add \222 -lactam Non-gonococcal urethritis/cervicitis/ C. tra- chomatis infection: 1 g \227 1 dose Non-TB mycobacterium (e.g., M. avium intracellul are [MAI] ): 500 mg/24 h as part of combination therapy MAI prophylaxis: 1,200 mg/wk Travel ers \200\231 diarrhea: 500 mg/24 h for 1 \200\2233 d Sinusitis/pharyngitis/otitis media/bro nchitis: 250 \200\223500 mg/12 h \227 7 d Pertussis: 500 mg/12 h \227 7 d Mild-moderate C AP: 250 \200\223500 mg/12 h \227 7 \200\22314 d Non-TB mycobacterium (e.g., MAI): 500 mg/1 2 h as part of combination therapy H. pylori ulcer: 500 mg/12 h as part of com- bination th erapy \227 10 \200\22314 d Azithromycin: Available as IV or oral therapy, gen- erally well tolerated . No change for d ecreased filtration glomerular rate (GFR) Clarithromycin: More GI upset than azithromy- cin, multiple drug interac- tions, mostly via P-450 metabolism. Decrease to q24h for CrCl <50 Quinolones Active against many community-acquired respiratory, GU, and GI pathogens. Member s of this class are available in oral and IV formulations and are the only oral option for susceptible Pseudomonas aeruginosa . Table 14.10 Quinolones 250 \200\223750 mg/12 h PO 200 \200\223400 mg/12 h IV Higher doses and longer courses for m ore compli- cated and severe infections Ciprofloxacin: Used in adult cystic fibrosis, typhoid, Salmonella , Campylobacter , prostat itis, and serious or resistant infections. Avoid overuse. CrCl <30:400 mg/24 h IV, PO: 250 \200\223500 mg/12 h PO, HD: 200 \200\223400 mg/ 24 h IV, 2 50 \200\223500 mg/24 h HD: Give dose after HD CrCl <50: 250 533 Levofloxacin: Less active against Pseudomonas Moxifloxacin: Less active against Pseudomonas , poor urine penetration 250 \200\223750 mg/24 h IV or PO mg/24 \200\22348 h IV 400 mg/24 h IV or PO No adjustment Carbapenems Very broad-spectrum activity against gram-positive, gram-negative, and anaerobi c bacteria. Stenotrophomonas, MRSA, and carbapenemase produc- ing gram-negative rods not su sceptible. Imipenem has better activity against E. faecalis than ertapenem and meropenem. C arbapenems may cause sei- zures, particularly imipenem. Table 14.11 Carbapenems 1 g/24 h IV Ertapenem: Not active against P. Aeruginosa and Acinetobacter. Imipenem/Cilastatin: Most li kely to cause seizures. CrCl <10: 500 mg/24 h HD: 500 mg/24 h and dose post HD 500 \200\2231,000 mg/6 \200\2238 h IV CrCl 40 \200\22370:500 mg/6 \200\2238 h IV,20 \200\22340: 250 mg/6 h or 500 mg/8 h, <20 250 \200\223500 mg/12 h HD: 250 mg/12 h + 250 mg after HD Consider meropenem with lower CrCl 1 \200\2232 g/8 h IV Meropenem: May be used in CNS infections CrCl 25 \200\22350: 1 g/8 \200\22312 h, 10 \200\22325: 500 \200\2231,000 mg/12 h, <10: 500 \200\2231,000 mg/24 h HD: 500 \200\2231,000 mg/24 h, dose after HD Table 14.12 Other antibiotics 1 \200\2232 g/6 \200\2238 h IV Aztreonam: Active against aerobic gram-negative rods, generally safe to use in PCN allergic patients CrCl l30 \200\22350: Q8 \200\22312h, 10 \200\22330: Q12h, <10: Q24h HD: 1 \200\2232 g/24 h, dose after HD or + 250 mg after HD Clindamycin: Active 150 \200\223300 mg/6 h PO; No renal 534 against gram-positive cocci including penicil- lin resistant staph, and anaerobes max 450 mg/6 h PO. 0.2 \200\2230.9 g/8 h IV or IM (by IV only, if >600 mg used 4 \200\22310 mg/kg/24 h IV adjustment Daptomycin: Broadly active against many aerobic gram posi- tives (including VRE and MRSA, V ISA), not active in lung infections. May cause myopathy <30 q48h (Continued) s e s a e s i d Table 14.12 (Continued) Doxycycline: Broadly 100 mg/12 h IV or PO No adjustment active many organisms including intracellular bacteria and spiro- chetes (e.g., rickettsia, Lyme, syphilis). Can cause photosensitiv- ity. Do not use in pregnancy. s u o i t c e f n I Linezolid: B roadly active against many aerobic gram-positives; myelo- toxicity and neuropa - thy with extended use, 600 mg/12 h PO or IV No adjustment Metronidazole: Drug of choice against anaerobes, Gardnerella , Entamoeba histolytica , and Giardia lamblia; mild to moderate C. difficile colitis 250 \200\223500 mg/12 h PO or 500 mg/6 h IV No adjustment Nitrofurantoin mono- hydrate macrocrys- tals: Broadly active against many UTI pathogens. Ma y cause pulmonary fibrosis UTI (uncomplicated) 100 mg/12 h PO CrCl <50: DO NOT USE, levels in urine inadequate and high serum levels may lead to toxicity No adjustment UTI prophylaxis: 50 \200\223100 mg/24 h Rifampin: Key compo- nent of combination therapy in TB and in salvage of infected orthopedi c devices. Associated with many drug interac- tions through P-450 metabolism Dose examples: 600 mg/24 h PO for TB, 600 mg/12 h \227 2 d for N. meningitis prophylaxis CrCl 10 \200\22330: 5 mg/ TMP/SMX: Drug of choice for preven- tion and treatment of Pneumocystis . Active against tox oplasmo- sis, many Nocardia, Stenotrophomonas, Listeria, community-ac- quired Staph aureus, E. coli . Allergic reactions, myelotoxicity, jaundice may occur. SS = 400 mg TMP/80 mg SMX, DS = 800 mg TMP/160 mg SMX kg/12 h 535 <10: Avoid TMP/ SMX if possible. If using: to 1/3 standard doses. GI/GU/Skin: 1 \200\2232 DS/12 h PO Serious invasive disease (e.g., PCP): 5 mg/kg (TMP component) /8 h HD: Dose after HD PCP Prophy laxis: 1 SS or DS/24 h or 1 DS every other day (Continued) Table 14.12 (Continued) Vancomycin (IV): 15 mg/kg/12 h IV, adjust dose by levels. Target trough: 15 \200\22320 for serious infection s CrCl 30 \200\22360: 15 mg/kg/24 h, <30: 15 mg/kg \227 1 then adjust dose by levels Broadly active against many aerobic gram- positives. Histamine release syndrome with rapid infu- sion. Potential for nephrotoxicity 125 \200\223500 mg/6 h No adjustment Vancomycin (oral): Moderate to severe C. difficile colitis Empiric treatment History A detailed history will usually reveal the source of infection. L isten to the paient! Ask about respiratory, skin, GI, GU, symptoms; any travel, sexual part ner, or possible immunocompromised state. Knowledge of local (including hospital) infectiou s diseases epidemiology and resistance pat- terns is essential in selecting the best empiri c regimen (see Table 14.13). Examination Evaluate the fever curve and examine for localizin g signs. Investigations Diagnostic testing should be driven by the results of the history a nd physical examination. Try to avoid \200\234fishing expeditions. \200\235 If pos- sible, culture all likely sources before treating (blood, sputum, urine, feces, skin/wound swabs, cerebrospinal fluid [CSF], aspirates). As appropriate, check CBC, urine analysis (U/A), er ythrocyte sedimentation rate (ESR), c-reactive protein (CRP), electrolytes, liver function tests (LFT), clotting, malaria movie, respiratory and serum viral studies, save acute-phase serum, radiographic imaging, arterial blood gas (ABG; as clinically indicated). Treatment Follow local guidelines. Change to the most appropriate drug once sensitivities are known. Treatment of most infections should not exceed 7 d. Intravenous antibiotic therapy should p referably not exceed 48 \200\22372 h; review the need and change to PO if possible. If in d oubt, ask for Infectious Disease consultation. Table 14.13 Empiric treatment Infection Treatment (with normal GFR) 536 Urinary tract infections UTI (uncomplicated) TMP/SMX 160/800 mg/12 h PO \227 3 d Nitrofurantoin monohydrate macrocrystals 100 mg/12 h PO \227 5 d Ciprofloxacin 250 mg/12 h \227 3 d Ciprofloxacin 400 mg/12 h IV or 500/12 h mg oral, ceftr iaxone 1 g/24 h IV, gentamicin 5 \200\2237 mg/kg/24 h IV UTI (pyelonephritis): Adjust therapy once susceptibilities known UTI with sepsis Many options, one approach is broad spectrum \222 -lactam (e.g., piperacillin/tazobactam, Cefepime) + aminoglycoside (Continued) s e s a e s i d Table 14.13 (Continued) Skin and soft tissue Incision and drainage. Not all MRSA skin infec- Abscess/furuncle/ carbuncle (MRSA suspected) tions require systemic therapy s u o i t c e f n I Cellulitis (nonpuru- lent): Length of therapy guided by response to anti- biotic. Elevation of affected limb is very important. Purulent cellulitis PO: Dicloxacillin 500 mg/6 h, cephalexin 500 mg/6 h, clindamycin 300 mg \200\223450 mg/8 h, amoxicillin/clavulanate 875 mg/12 h IV: Cefazolin 1 g/6 \200\2238 h, ampicillin/sulbactam 1.5 g/6 h, ceftriaxone 1 g/24 h, clin damycin 600 mg/8 h. PO: TMP/SMX 1 \200\2232 DS tabs/12 h, clindamycin 300 \200\223450 mg/8 h, doxycycline 100 m g/12 h, linezolid 600 mg/12 h (MRSA suspected) IV: Vancomycin 15 \200\22320 mg/kg/8 \200\22312 h, dapto- mycin 6 mg/kg/24 h, linezolid 600 mg/24 h, clindamycin 600 mg/8 h, telavancin 10 mg/ kg/d Diabetic foot infection: Management requires multidisciplinary approach Mild (PO): Dicloxacillin, cephalexin 500 mg/6 h, clindamycin 300 mg \200\223450 mg/8 h, TMP / SMX 2 DS tabs/12 h, amoxicillin/clavulanate 875 mg/12 h, levofloxacin 500 mg/d, Moderate (PO): TMP/SMX 2 DS tabs/12 h, amoxicillin/875 mg/12 h, ciprofloxacin 500 mg/12 h + either metronidazole 500 mg/8 h or clindamycin 300/8 h Moderate (IV): Ertapenem 1 g/24 h, ampicil- lin/sulbactam 3 g/6 h, Severe (IV): Piperacillin/tazobactam 4.5 g/6 h vancomycin 15 \200\22320 mg/kg/8 \200\22312 h Life- or limb-threaten- ing soft-tissue infec- tion: Obtain surgical evaluation IV: Many options, one approach: Piperacillin/ tazobactam 4.5 g/6 h + vancomycin 15 \200\223 20 mg/kg/8 \200\22312 h + clindamycin 600 mg/8 h (if deep tissue infection) Surgical wound infec- Following clean procedures: Treat as nonpu- rulent cellulitis. If concern for MRSA, treat w ith vancomycin. Following contaminated procedures: Piperacillin/tazobactam and vancomycin tion: If possible, await deep swab results. Strongly consider wound exploration. 537 Pneumonia: Pathogens differ between community-acquired (CAP), hos- pital-acquired (HAP) and ventilator-acquired (VAP) Mild CAP (ambulatory), otherwise healthy Mild-moderate CAP Azithromycin 500 mg/24 \227 5 \200\22310 d Clarithromycin 250 \200\223500 mg/12 h \227 7 \200\22314 d Respiratory quinolones (e.g., moxifloxacin 400 (ambulatory) mg/24 or levofloxacin 750 mg/24 h \222 -lactam (e.g., amoxicillin 1 g/8 h, amoxicillin/ clavulanate 2 g/12 h) + macrolide Moderate CAP (inpatient) Respiratory quinolones \222 -lactam (e.g., ceftriaxone 1 g/24 h) + macrolide (Continued) Table 14.13 (Continued) Severe CAP (inpatient) \222 -lactam (e.g., ceftriaxone) + either a mac- rolide or respiratory quinolone. If risk for pseudomonas use cefepime or piperacillin/ tazo bactam as \222 -lactam HAP and early onset Respiratory quinolone or \222 -lactam (e.g., ceftri- VAP axone) macrolide. If risk for pseudomonas use cefepime or piperacillin/tazobactam as \222 -lactam Late onset VAP (>72 hours of hospitalization) Antipseudomonal \222 -lactam (e.g., cefepime, piperacillin/tazobactam) + vancomycin ami noglycoside Bacterial meningitis: In adults with suspected or proven pneumococcal meningitis, dexametha sone (0.15 mg/kg/6 h) should be given just before or with the first dose of antibiotics and continued for 2 \200\2234 d. Adult \222 50: (cid:2) S. pneumo- niae, N. meningitidis, H. influenzae , Group B strep) Vancomycin 15 \200\22320 mg/kg/8 \200\22312 h IV + ceftriax- one 2 g/12 h IV Adult <50 or immuno- compromised: Also, Listeria and aerobic gram-negative rods Following p enetrating head trauma or neu- rosurgery: Aerobic gram-negative rods and staphylococci If H SV encephalitis Vancomycin IV + ceftriaxone IV + ampicillin 2 g/4h IV Vancomycin IV + either cefepime 2 g/8 h IV or meropenem 2 g/8 h IV Add acyclovir 10 mg/kg/8 h IV possible Bacterial endocarditis (native valve): If at all possible, therapy should be driven by orga nism identified on culture. S . viridans and S. bovis PCN-G 3 million units/4 \200\2236 h IV or ceftriaxone (MIC \222 0.12) 2 g/24 h IV \227 4 wks S. viridans and S. bovis (MIC >0.12, \222 0.5) PCN-G 4 million units/4 h or 6 MU/6 h IV or ceftriaxone 2 g/24 h IV and gentamicin 3 mg/kg/ 24 h IV for first 2 wks S. viridans and S. Ampicillin 2 g/4 h IV or PCN-G 3 \200\2235 million 538 bovis (MIC >0.5), Enterococcus (PCN susceptible) units/4 h IV and gentamicin 1 mg/kg/8 h IV MSSA MRSA HACEK organisms: Oxacillin 2 g/4 IV, cefazolin 2 g/6 h IV \227 6 wks Vancomycin 15 \200\22320 mg/kg/12 h IV Ceftriaxone 2 g/24 h IV, ampicillin/sulbactam 3 g/6 h IV \227 4 wks Haemophilus parain- fluenzae, H. aphro- philus, Actinobacillus actinomycetemcomi- tans, Car diobacterium hominis, Eikenella cor- rodens, and Kingella kingae s e s a e s i d Table 14.13 (Continued) Culture negative: Effort should be made to establish microbio- logic diagnosis Ampicillin/sulbactam 3 g/6 h IV and gentamicin 1 mg/kg/8 h IV X 4 \200\2236 wks s u o i t c e f n I Prosthetic valve endocarditis: Management requires a multidisci- plinary approach and shoul d be directed toward specific pathogen as soon as feasible Initial therapy Vancomycin 15 \200\22320 mg/kg/12 h + gentamicin 1 mg/kg/8 h + rifampin 900 mg/24 h Intra-abdominal infections: In addition to antibiotics, patients should be evaluated for surgical management/source control. Mild-moderate Piperacillin/tazobactam 3.375 g/6 h IV, ertap- enem 1 g/24 h IV, moxifloxacin 400 mg/24 h, or metronidazole 500 mg/6 \200\2238 h + either cephalosporin or quinolone, Severe Piperacillin/tazobactam IV, meropenem 2 g/8 h IV, imipenem/cilastatin 500 mg/6 h IV, or met ronidazole + Cipro or cefepime IV Sepsis in ICU without clear etiology: Piperacillin/tazobactam 4.5 g/6 h or Cefepime 2 g/8 h vancomycin 15 \200\22320 mg/kg/6 \200\2238 h, aminoglycoside Osteomyelitis/septic ar thritis/discitis: Make every effort to obtain microbiological diagnosis. In case of spine i nfections, closely evaluate for neurological injury: Vancomycin 15 \200\22320 mg/kg/6 \200 \2238 h IV late generation cephalosporin (e.g., ceftriaxone 2 g/24 h or Cefepime 2 g/8 h IV) Adult immunization Active immunization usually stimulates the immune system (humoral and ce llular immunity). Passive immunization provides preformed anti- body (nonspecific or antige n-specific). Table 14.14 Adult immunization Vaccine Influenza Comment Annually, intranasal OK for healthy, nonpreg- nant adults age <50. Others should re ceive injection. Tdap once and then Td every 10 yrs 539 Tetanus, diphtheria (Td) + acellular pertussis (Tdap) Varicella Two doses if not immune. Contraindicated in immunocompromised and pregnant women. HPV2 or HPV4 Three doses through age 26 (females), HPV4 may be given to males through age 26. One dose a ge >65. Contraindicated in Zoster immunocompromised and pregnant women. (Continued) Table 14.14 (Continued) Vaccine Measles, mumps, rubella Comment Born before 1957: 1 \200\2232 doses, after 1957 (MMR) (without evidence for immunity): 1 \200\2232 doses. Contraindicated in immunocompro- mised and pregnant women. Pneumococcal Age >65, chronic medical condition (e.g., lung, polysaccharide liver, sickle cell, asplenia, immunocom- promised, cochlear implants, CSF leaks), tobacco u se: 1 dose, 5-yr booster. Meningococcal Expected to have exposure (e.g., first-year col- lege students, military recruits, microbio lo- gists, travelers to endemic area or Hajj: 1 dose (2 doses in such patients who also hav e HIV). Asplenia, complement deficiency: 2 doses. Men who have sex with men, injection drug use, ch ronic liver disease, travelers to endemic area: 2 doses. Hepatitis A Hepatitis B Patients at risk for exposure (e.g., through occupation, sexual activity, injection drug use, prison), those with chronic liver, renal, and HIV disease: 3 doses. Haemophilus influenza (HiB) Previously unvaccinated patients with HIV, asplenia, sickle cell, leukemia. Recommended adult immunization schedule \200\224 United States, 2011. MMWR . February 4, 2 011;60(4). Drug abuse and infectious diseases Clues to substance abuse \212 \212 \212 Request for analgesics from multiple providers Transient residency in the area Demand for a nalgesia/antiemetic and specific requests for medications on your institution \200\231s for mulary Erratic behavior in the clinic or ward; unusual absences and/or visitors; mood swing s Patient is difficult to arouse in the mornings; agitation from day 2 Heavy smoking; stran ge smoke smells (cannabis, cocaine, and heroin) \212 \212 \212 Physical clues \212 \212 \212 \212 \212 540 Acetone or glue smell on breath (solvent abuse) Small pupils on eye exam (opiates), reverse d by naloxone Needle tracks on arms, groin, legs, between toes, and difficult IV access Abs cesses and lymphadenopathy in nodes draining injection sites Evidence of illnesses associat ed with substance abuse (e.g., endocarditis, HIV, chronic viral hepatitis) Common and possible presentations in drug abusers s e s a e s i d Table 14.15 Drug abuse presentation Unconscious Narcotics (consider naloxone), barbiturates, solvents, benzodiazepines Ecstasy, LSD, amphet amine, anabolic steroids, benzodiazepines. Haloperidol may help. Consider opiate-induced pu lmonary edema. Asthma may follow the smoking of heroin. Right-sided endocarditis ( S. aureu s ) until proved s u o i t c e f n I Psychosis or agitation Asthma or dyspnea Lung abscess otherwise Is it endocarditis? Fever/FUO Shivering and headache After a \200\234bad hit \200\235 (chemical/organism conta mi- nation). Beware of myoglobinuria, DIC, renal failure. Obtain blood cultures and consider em piric antibiotics Abscesses If over injection site, then often of mixed organisms. DVT Pneumonia Due to injections into groin. Pneumococcus, Haemophilus , Tuberculosis (TB), Pneumocystis Tachyarrhythmia Jaundice (If young); cocaine, amphetamines, endocarditis Hepatitis B, C, or D; anabolic steroids (cholestasis) Lymphadenopathy with May be presentation of HIV seroconversion fever illness Osteomyelitis Including spinal and sternoclavicular infections. Consider S. aureus /gram-negative organis ms Constipation Blindness Runny nose If severe, opiate abuse may be the cause. Consider fungal endophthalmitis, septic emboli. O piate withdrawal (colic/diarrhea, yawns, lac- rimation, dilated pupils, insomnia, myalgias, mood \206\223 ; cocaine use) Consider solvent abuse. Suspect cocaine use or septic emboli . Neuropathies Infarctions nal cord, myocardium of spi- brain, 541 General management A nonjudgmental approach will produce better cooperation and may avoid t he patient leaving against medical advice. Establish firm rules and, if necessary, a writte n contract of acceptable behavior. NSAIDs are useful for pain relief. Try to avoid prescrib ing benzodiazepines. Many people trade sex for drugs. If evidence of unsafe sex behaviors, need sexually transmitted disease (STD) screen and cervical cytology (women) as carcinoma i n-situ is common. Screen for HIV, hepatitis B, C (provide vac- cination when indicated); sa fer sex and safer injection advice. Fever of unknown origin Consider the type of patient Classical Fever of unknown origin (FUO ) is defined as a prolonged fever (>3 wks), temperature 38.3 , undiagnosed despite 3 d of testing in the hospital, or 2 or more outpatient visits. Main causes of this type of FUO are infec- tions, rheumatic/connective tissue disease, neoplasm, and miscellaneous. In up to 30% of patients a diagnosis is not achieved. In general, fevers that persist despite a p rolonged and intense search for diagnosis are less likely to be due to infection. Bacteremi a is not a common cause of FUO. FUOs in immunocompromised patients : Typically due to infec tions or im- mune reconstitution. Health care-associated FUO: Defined as illness that devel oped while in hos- pital with temperature 38.3 for 3 d. This is usually due to infecti ons and iatrogenic (e.g., postsurgical, drug fever) complications. Infectious: Most classic al infectious FUOs are due to TB, subacute and cul- ture-negative endocarditis, intraabdomi nal and pelvic abscesses, EBV, CMV, typhoid fever, and cat scratch disease. Less common cau ses of FUO include chronic sinusitis, relapsing fever, toxoplasmosis, Whipple \200\231s dis ease, visceral leishmaniasis, HIV, Q fever, brucellosis, trichinosis, trypanosomiasis, ma- laria, schistosomiasis, histoplasmosis, and coccidioidomycosis. Evaluation for presence of rare and unlikely infections may lead to unnecessary and useless tests. Pitfalls: Chest rad iograph may be negative in TB and diagnosis may require culture of sputum, urine, and gastr ic aspirate. Blood cultures may be negative with endocarditis. Neoplasm: Especially lymphom as (HL and NHL), myeloma, renal cell carci- noma (hypernephroma). Occasionally, fevers are due to solid tumors (es- pecially with hepatic metastasis \200\224breast, lung, GI). Fever with leukemia is usually due to infection. Connective tissue disease: Rheumatoid arthritis, polymyalgia rheumatica, still \200\231s disease, giant cell arteritis, granulomatous hepat itis, systemic lupus erythematosus (SLE), polyarteritis nodosa (PAN), Kawasaki \200\231s di sease. Others: Drug fever (fever may occur months after starting but remits within days of stopping; eosinophilia is an inconsistent clue); pulmonary embolism; stroke; Crohn \200\231 s; ulcerative colitis; sarcoid; amyloid; factitious fever, familial Mediterranean fever \200\224recurrent polyserositis (peritonitis, pleurisy) + fevers, abdominal pain, and arthr itis; treat with colchicines. Fever patterns May offer some information, but are rarely dia gnostic and can be altered by widespread use of antipyretics and empiric antibiotics. \212 Intermittent: SBE; TB, filarial fever, amyloidosis, brucellosis \212 \212 Abscess, malaria, schistosomiasis Fever that resolves for a few d and then returns: Daily fever spikes: Saddleback fever: Colorado tick fever, borreliosis, Leptospirosis, deng ue, ehrlichiosis Longer periodicity: Remitting: salmonellosis, Kawasaki disease, CMV 542 \212 \212 Pel \200\223Ebstein. Diurnal variation, not dipping to normal. Amebiasis, malaria, History Ask about weight changes, sweats, cough, sinus congestion, mild diarrhea, rashes an d itching, bites, cuts, surgery, implanted medical devices, drugs (including nonprescriptio n), immunization, cardiac valve problems, immunosuppressive illness, sexual history, travel , former residences, hobbies, occupations, IV drug abuse, animal exposures, sick contacts, and family history. If a patient has been to an exotic locale, find an expert on that area or else you might miss diagnoses you may have never heard of. Examination Verify fever , pe rform a thorough physical exam. Repeated exams are often required. Remember eyes, teeth, re ctal/vaginal exams, skin lesions, lymphadenopathy, hepatosplenomegaly, nails, joints, and temporal arteries. Tests S tage 1(the \201 rst day): CBC, ESR, electrolytes, LFTs (especially alkaline phos- phatase ), CRP, white blood cell (WBC) differential, save acute-phase se- rum, blood cultures (seve ral, from different veins, at various times of day; prolonged culture may be needed for Bru cella spp.); baseline serum for virology, sputum microscopy and culture (specify for TB), u rine dipstick, microscopy, and culture stool for microscopy (ova, cysts, and parasites), ch est x-ray (CXR). Stage 2: Repeat history and examination, obtain protein electrophoresis, c omputed tomography (CT) (chest, abdomen), rheumatoid factor, anti- nuclear antibodies (ANA) , antistreptolysin titer, purified protein derivative (PPD) or interferon -release assay (IGRA), electrocardiogram (ECG), con- sider bone marrow biopsy and lumbar puncture. Consid er prostate-specific antigen (PSA), carcino-embryonic antigen (CEA), and withholding drugs, one at a time for 48 h each. Consider temporal artery biopsy, HIV (with counseling). Stage 3: Follow any leads uncovered. Consider echocardiography, CT, liver biopsy, bronchoscopy. Empiric treatment Except in the case of neutropenia and otherwise very immunosuppressed pat ients, hold off, if possible, on antimicrobial therapy for FUO until a diagnosis is establi shed. An empiric trial for TB or endocarditis may be attempted in selected patients. A tria l of steroids should be considered early if there is suspicion for temporal arteritis. s e s a e s i d s u o i t c e f n I Gastroenteritis Ingestion of certain bacteria, viruses, and toxins (bacterial and chemical) is a common cause of diarrhea and vomiting (Table 14.16). Contaminated food and water are common sources but often no specific cause is found. Ask about details of stool characteris tics, food and water taken, cook- ing method, time for onset of symptoms, and whether other diners were affected. Ask about travel, sexual activity, swimming, canoeing, and expo- sur e to day-care centers. Table 14.16 Causes of gastroenteritis Causative agent Incubation period 10 \200\22360 min Diarrhea, flush- Predominant Clinical features Food associations Fish or Swiss cheese Scombrotoxin ingestion 543 ing, erythema, hot mouth Nausea, vomiting, Red kidney bean poisoning (phy- tohemagglutinin ingestion) 1 \200\2233 h Undercooked or raw kid- ney beans diarrhea Ciguatera poisoning Nausea, vomit- ing, diarrhea, perioral tingling/numb- ness, range of neurological symptoms Warm-water fish (Continued) Table 14.16 (Continued) Causative agent Incubation period 1 \200\2236 h Predominant Clinical features Nausea, vomiting, Food associations Range of foods, esp. meats S. aureus (preformed toxin) cramping, may cause hypotension Nausea, vomiting, Bacillus cereus (pre- formed toxin) 1 \200\2236 h Rice and other starchy products Range of foods cramps Bacillus cereus (toxin produced in vivo) Clostridium perfringens (toxin produced in vivo) 8 \200\22316 Diarrhea, cramps 8 \200\22324 h Diarrhea, cramps Meats Clostridium botulinum 12 \200\22336 h Double vision, ver- tigo, symmetric descending paralysis Diarrhea with \200\234rice water \200\235 stool Home-canned (toxin) food Vibrio cholera (pro- 2 h \200\2235 d Contaminated water due to poor sanitation duce toxin in small intestine) Vibrio parahaemolyti- 12 \200\22324 h Vomiting, cramps, Seafood cus (produce toxin in small intestine) Noroviruses, enteric adenovirus, parvo- virus, calic ivirus, enteroviruses diarrhea 1 \200\2235 d Nausea, vomit- ing, diarrhea, cramping Contaminated food/water Rotavirus 1 \200\2237 d Vomiting, diarrhea, low-grade fever Vomiting, diarrhea, abdominal pain, fever, septicemia Contaminated food Meat, eggs, poultry Salmonella spp. 12 \200\22348 h Yersinia entero- 24 \200\22336 h Diarrhea, fever, Meats, seafood, raw milk colitica and Y. pseudotuberculosis abdominal pain, may mimic appendicitis Diarrhea (may 544 Campylobacter spp. 2 \200\2235 d Undercooked have red blood cell [RBC] or WBC), abdominal pain, headache, myal- gias, fever Bloody diarr hea, tenesmus, pus in stools, abdominal pain, fever chicken, raw milk, non- chlorinated water Shigella spp. 12 \200\22350 h Any food (Continued) s e s a e s i d Table 14.16 (Continued) Causative agent Incubation period 12 \200\22372 h Predominant Clinical features Bloody diarrhea, hemolytic-ure- mic syndrome Diarrhea, cramps , low-grade fever Food associations Undercooked hamburger meat E. coli type 0157:H7 s u o i t c e f n I E. coli Contaminated water/food in developing countries Undercooked (enterotoxigenic) E. coli Watery or bloody (enteropathogenic) diarrhea, Meningoen- cephalitis, septicemia, often preceded by influenza- like symptoms, so metimes GI symptoms Diarrhea, may be bloody, fever, leuko- cytosis, may lead to toxic megac olon/ perforation meat Listeria monocytogenes Days to weeks Meats, cheese, p t s, raw milk Clostridium difficile Antibiotic exposure Cryptosporidium 4 \200\22312 d Diarrhea Contaminated water/food, manure Contaminated Giardia lamblia 1 1 \200\2234 wks Diarrhea, lactose intolerance Diarrhea, abdomi- water Balantidium coli Variable, often asymp- tomatic Contaminated nal pain water Characteristic Community acquired or recent Testing (stool) Salmonellosis, Shigellosis, E. coli travel Nosocomial >7 d of symptoms and/or immuno- 0157:H7 C. difficile Cryptosporidium , Giardia , 545 suppressed patients Cyclospora , Isospora , lactofer- rin, Salmonella , Shigella , E. coli 0157:H7. Add Microsp oridia and MAI, CMV, lymphoma in highly immunosuppressed. (Continued) Table 14.16 (Continued) Management is usually symptomatic. Maintain oral fluid intake ( oral rehydration solution ). For severe symptoms (but not in dysen- tery), give antiemetic (e.g., prochlorperazine 12 .5 mg/6 h IM) and an antidiarrheal (e.g., codeine 30 mg PO/IM or loperamide 4 mg initially then 2 mg after each loose stool). In general, routine antibiotics may cause more harm than good, and antimotility agents should be avoided in those with C. difficile infection. Anti biotics are generally recommended in travelers \200\231 diarrhea (often Enterotoxigenic E. coli ) and in patients who are systemically unwell, immunosuppressed, or elderly. Treat all typhi species of Salmonella and non-typhi in patients who are >50, or have prosthetic devi ces, severe atherosclerosis, valvular heart disease, cancer, uremia. Organism Vibrio choler a Treatment (when electing to treat) Doxycycline 300 mg PO \227 1, TMP/SMX DS/12 h PO \227 3 d, ciprofloxacin 1 g PO \227 1, Azithromycin 1 g PO \227 1 Salmonella TMP/SMX DS/12 h PO, Ciprofloxacin 500 mg/12 h PO, ceftriaxone 1 \200\2232 g/24 h IV X 5 \200\2237 d (lon- ger if immunocompromised or extraintestinal) TMP/SMX DS/12 h PO, ciproflo xacin 500 mg/12 h PO, azithromycin 500 mg \227 1, then 250 mg/12 h PO, ceftriaxone 1 \200 \2232 g/24 h \227 3 \200\2235 d (longer if immunocompromised) Shigella Campylobacter Erythromycin 500 mg/12 h PO \227 5 d (longer if immunocompromised) E. coli species (except enterohemorrhagic) TMP/SMX DS/12 h PO, ciprofloxacin 500 mg/12 h PO \227 3 d C. difficile: STOP Metronidazole 500 mg/8 h PO or oral vancomy- causative antibiotic if possible cin 125 \200\223250 mg/6 h \227 10 d or longer Cyclospora, Isospora TMP/SMX DS/12 h PO \227 7 \200\22310 d (consider q6h and longer in immunocompromised) Metronidazole 250 \200\223500 mg/8 h \227 7 \200\22310 d Metronidazole 750 mg/8 h \227 7 \200\22310 d + luminal Giardia E. histolytica agent (iodoquinol 650 mg/8 h \227 20 d or paro- momycin 500 mg/8 h \227 7 d) Balantidium coli Tetracycline 500 mg/6 h \227 10 d, iodoquinol 650 mg/8 h \227 20 d, metronidazole 750 mg/ 8 h \227 5 d 546 Bad Bug Book: Foodborne Pathogenic Microorganisms and Natural Toxins Handbook . Washington, DC: U.S. Food and Drug Administration, 2012. Evaluating the tropical traveler In every ill traveler, consider Malaria: Presentation : Fe ver, rigors, headaches, dizziness, flu-like symptoms, diarrhea, and thrombocytopenia. Compl ications: Anemia, parasite counts >5%, renal failure, pulmonary edema, cerebral edema. Diag nosis: Serial thick and thin blood films. Note : Mosquitoes may stowaway in luggage causing malaria in nontropical areas. Typhoid: Presents with fever, relative bradycardia, abdominal pain, dry cough, constipation , lymphadenopathy, headache, and splenomegaly rose spots (rare). Complications: GI perfo ration. Diagnosis: Blood or stool culture. Dengue fever: Presents with fever, headache, mya lgias, rash (flushing or petechial), thrombocytopenia, and leucopenia. Diagnosis: Serology. Amoebic liver abscess: Presents with fever, jaundice, right upper quadrant (RUQ) pain. Do serology and ultrasound. Blood cultures to rule out septicemia. See Table 14.17. A visit to the tropics does not preclude the mundane fevers (e.g., flu). Jaundice Think of viral hepa titis, cholangitis, liver abscess, leptospirosis, typhoid, malaria, dengue fever, yellow fe ver, and hemoglobinopathies. Hepatosplenomegaly leishmaniasis, schistosomiasis, toxoplasmos is. Gross splenomegaly Malaria, visceral leishmaniasis (kala-azar). Diarrhea and vomiting E nterotoxigenic E. coli (travelers \200\231 diarrhea) is most common. Consider Salmonella , Shigella , Campylobacter , Giardia lamblia, Vibrio cholerae, Yersinia, Cryptosporidium, Iso spora, E. coli 0157, Enteroinvasive E. coli, Aeromonas, Rotavirus, Noroviruses, etc. If dia rrhea prolonged, consider protozoal infection of small bowel or tropical sprue. In HIV: MAC , CMV, Cryptosporidium, Microsporidium , and Isospora belli . Respiratory symptoms Common r espiratory pathogens, typhoid, Legionella , TB, Q fever, histoplasmosis, L ffler \200 \231s syndrome. Arthritis Gonococcus; septicemia; viruses (Ross River, Chikungunya). Erythe ma nodosum Causes: Strep, TB, leprosy, fungi, Crohn \200\231s, ulcerative colitis, sarcoido sis, pregnancy, drugs (sulfonamides). Anemia Hookworm, malaria, kala-azar, hemolysis, and m alabsorption. Skin lesions Scabies (itchy allergic rash + burrows, e.g., in finger web- spa ces), bed bugs (grouped papules), myiasis (nodules \200\224larvae of various insects), orf (pustules), molluscum contagiosum (pearly, punctate, papules), leprosy (anesthetic, hypopig mented areas), Loa loa (calabar swellings), cercarial dermatitis (swimmer \200\231s itch), leishmaniasis (ulcers/nodules), rickettsial infections (African tick typhus, Mediterranean tick typhus, scrub typhus [painless eschar = scab]), drug reactions. Acute abdomen Perforat ion of a typhoid ulcer, toxic megacolon in amoebic or bacillary dysentery, sickle-cell cris is, ruptured spleen. Rarities to consider Use local emergency isolation policy. Rabies and other CNS viral infections (e.g., encephalitis). Yellow fever : Suspect in travelers from A frica. Lassa fever: Occurs in Nigeria, Sierra Leone, or Liberia. Signs: Fever; sore throat with exudates, face edema; shock. Marburg and Ebola virus: Seen in Sudan, Zaire, and Kenya. Signs: Fever, myalgias, diarrhea, nausea and vomiting (N&V), pleuritic pain, hepatitis, sh ock, and bleeding tendency. Maculopapular rash appears on day 5 \200\2237 and desquamates i n <5 d. Patients may bleed from all orifices and gums. Viruses that cause hemorrhage: Dengu e, Marburg, Lassa, Ebola, Crimea-Congo fever, hemorrhagic fever with renal syndrome, yellow fever. s e s a e s i d s u o i t c e f n I Viral hepatitis, malaria, Brucella , typhoid, 547 Table 14.17 Incubation times for fever in the tropical traveler The incubation times below are typical, but considerable variation occurs. <14 d Undifferen tiated fever Malaria Typhoid Leptospirosis Acute HIV infection Dengue fever Rickettsial 2 \200\2236 wks >6 wks Acute schistosomiasis Hepatitis E Hepatitis A Amoebic liver abscess Lymphatic filariasis Kala-azar Hepatitis B