Infectious Disease

Harriet Lane Guidelines Chapter 17



TABLE 17-1   -- COMMON PITFALLS BETWEEN IN VITRO AND IN VIVO ANTIBIOTIC SENSITIVITY PROFILES
BacteriaIn Vivo ResistanceRecommendations
StaphylococciMethicillin- resistantStaphylococcus aureus (MRSA)If MRSA is reported to be susceptible to clindamycin in vitro, but resistant to erythromycin, a D test (double disk diffusion assay) is recommended to look for in vitro macrolide-inducible clindamycin resistance. If D test is positive, MRSA may have inducible resistance to clindamycin; consider using vancomycin, TMP- SMX, or linezolid for serious infections.
SalmonellaAminoglycosidesDespite in vitro susceptibility to aminoglycosides, salmonella are not susceptible in vivo to this class of antibiotics. Ampicillin/amoxicillin, TMP-SMX, or cephalosporins preferred.
Enterobacter spp.CephalosporinsAll are inducibly resistant to all cephalosporins, which should not be used as sole treatment for invasive or serious infections caused by these organisms. Because β-lactamase inhibitors are potent inducers of cephalosporin resistance, and they do not overcome resistance in these organisms, β-lactamase inhibitors should not be used.[3]
Citrobacter spp.
Pseudomonas aeruginosa
Serratia spp.
Providencia spp.
Morganella spp.
Burkholderia cepaciaAminoglycosidesStenotrophomonas species are often only susceptible to TMP-SMX, the drug of choice in most cases for these organisms. Burkholderia often requires a carbapenem plus additional agents.
Stenotrophomonas maltophilia
P. aeruginosaTMP-SMXP. aeruginosa and Acinetobacter species are usually susceptible to aminoglycosides, but are resistant to TMP-SMX (despite reported in vitro susceptibility).
Acinetobacterspp.
EnterococciMost single-agent antibiotic classes
Vancomycin- resistant enterococcus (VRE)
Usually requires double-agent therapy for synergy and bacterial killing for invasive infections. Recommended therapy is ampicillin (vancomycin if ampicillin resistant). Add an aminoglycoside (preferably gentamicin or streptomycin) for serious invasive infections. Other antibiotics with activity against enterococci include amoxicillin, penicillin, piperacillin, and imipenem.
VRE is usually Enterococcus faecium, although rarely E. faecalis. Linezolid is active against most enterococcal isolates, including VRE. Quinupristin/dalfopristin (Synercid) is active against most E. faecium, including VRE, but not against E. faecalis. The following antibiotics are not clinically active against enterococci: all cephalosporins, antistaphylococcal penicillins (e.g., oxacillin), macrolides, clindamycin, and quinolones.

TMP-SMX, trimethoprim-sulfamethoxazole.



TABLE 17-9   -- THERAPY FOR CHLAMYDIA, GONORRHEA, AND PELVIC INFLAMMATORY DISEASE
Type or StageFirst-Line Drug and DosageAlternatives
CHLAMYDIA TRACHOMATIS
Urethritis, cervicitis, or proctitisDoxycycline 100 mg PO bid ? 7 days (if >9 yr) or Azithromycin 1 g PO ? 1 doseErythromycin base 500 mg PO qid ? 7 days or
Erythromycin ethylsuccinate 800 mg PO qid ? 7 days or
Ofloxacin 300 mg PO bid ? 7 days (if >18 yr)
Levofloxacin 500 mg PO daily ? 7 days
Infection in pregnancyErythromycin base 500 mg PO qid ? 7 days or 250 mg PO qid ? 14 daysErythromycin ethylsuccinate 400 mg PO qid ? 14 days or
Azithromycin 1 g PO ? 1 dose or amoxicillin 500 mg PO tid ? 7 days (alternative but less effective regimen)
Neonatal ophthalmiaErythromycin base or ethylsuccinate 50 mg/kg/24 hr PO or IV ? qid ? 14 daysTopical treatment is ineffective.
Neonatal pneumoniaErythromycin base or ethylsuccinate 50 mg/kg/24 hr PO or IV ? qid ? 14 daysNote: Association between PO erythromycin and pyloric stenosis has been reported.
GONORRHEA[*]
Newborns
Sepsis, arthritis, meningitis, scalp abscessCeftriaxone 25–50 mg/kg/24 hr IV/IM q24 hr ? 7 days (10–14 days if meningitis)
Neonatal ophthalmiaCeftriaxone 25–50 mg/kg (maximum 125 mg) IV/IM ? 1 dose plus saline irrigation orAll infants should receive silver nitrate, tetracycline, or erythromycin ointment instilled into each eye within 1 hr of birth. Note: All infants with gonococcal conjunctivitis should be evaluated for possible sepsis/disseminated disease and the need to be treated for a longer time.
Cefotaxime 100 mg/kg per dose IM/IV ? 1 dose
Prepubertal children who weigh <100lb (45 kg)
Uncomplicated urethritis, vulvovaginitis, proctitis, or pharyngitisCeftriaxone 125 mg IM ? 1 doseSpectinomycin 40 mg/kg (maximum 2 g) IM ? 1 dose + erythromycin 50 mg/kg/day in 4 divided doses ? 7 days or Azithromycin 20 mg/kg (max 1 g) ? 1 dose
Bacteremia, peritonitis, or arthritisCeftriaxone 50 mg/kg/24 hr (maximum 1 g) IM/IV q24 hr ? 7–10 days and erythromycin, doxycycline, or azithromycin
Children who weigh =100lb (45 kg) and are ≥ 9 yr
Uncomplicated endocervicitis, urethritis, or proctitisCeftriaxone 125 mg IM ? 1 dose orCefixime 400 mg PO ? 1 dose orCefotaxime 500 mg IM ? 1 dose or
Cefoxitin 2 g IM ? 1 dose with probenicid 1 g PO ? 1 dose
 Spectinomycin 2 g IM ? 1 dose orSome evidence indicates that cefpodoxime 400 mg and cefuroxime axetil 1 g might be oral alternatives.
 Ceftizoxime 500 mg IM ? 1 dose or 
 Doxycycline 100 mg PO bid ? 7 days 
PharyngitisCeftriaxone 125 mg IM ? 1 dose 
Disseminated gonococcal infectionsCeftriaxone 1 g/24 hr IV/IM q24 hr for 24–48 hr after clinical improvement, then switch to one of the following for at least 1 wk of therapy:Cefotaxime or ceftizoxime 1 g IV q8 hr for 24–48 hr after clinical improvement, then switch to oral therapy for 1 wk
 Cefixime 400 mg PO bid orFor persons allergic to β-lactam drugs: Spectinomycin 2 g IM q12 hr ? 7 days
 Cefixime suspension 500 mg PO bid orFluoroquinolones may be alternative treatment if antimicrobial susceptibility can be documented by culture.
 Cefpodoxime 400 mg PO bid 
EpididymitisCeftriaxone 250 mg IM ? 1 dose +If acute epididymitis most likely caused by enteric organisms, or with negative gonococcal culture: Ofloxacin 300 mg PO bid ? 10 days or levofloxacin 500 mg PO q24 hr ? 10 days
 Doxycycline 100 mg PO bid ? 10 days 
Bacteremia or arthritisCeftriaxone 50 mg/kg/day (maximum dose 1 g) IM or IV q24 hr ? 10–14 days
PELVIC INFLAMMATORY DISEASE (PID)
Parenteral regimenRegimen A 
 Cefotetan 2 g IV q12 hr orAmpicillin/sulbactam 3 g IV q6 h +
 Cefoxitin 2 g IV q6 hr + 
 Doxycycline 100 mg IV/PO q12 hrDoxycycline 100 mg PO/IV q12 hr
 Regimen B 
 Clindamycin 900 mg IV q8 hr + 
 Gentamicin 2 mg/kg loading dose, then 
 Gentamicin 1.5 mg/kg IV q8 hr maintenance dose 
Oral regimenCeftriaxone 250 mg IM ? 1 dose +Ceftizoxime or cefotaxime + Doxycycline 100 mg PO bid ? 14 days +/− Metronidazole 500 mg PO bid ? 14 days
 Doxycycline 100 mg PO bid ? 14 days +/− 
 Metronidazole 500 mg PO bid ? 14 daysorIf parenteral cephalosporin is not feasible, fluoroquinolones (levofloxacin 500 mg PO daily or ofloxacin 400 mg PO bid ? 14 days) +/− metronidazole (500 mg PO bid ? 14 days) may be considered if community prevalence and individual risk of gonorrhea are low.
 Cefoxitin 2 g IM ? 1 dose and probenicid 1 g PO ? 1 dose + 
 Doxycycline 100 mg PO bid ? 14 days +/− 
 Metronidazole 500 mg PO bid ? 14 days 
From Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines. MMWR 2006;55(RR-56) and Updated recommended treatment regimens for gonoccocal infections and associated conditions. MMWR April 2007;56(14):332–336.
*Therapy should include treatment for presumed concomitant chlamydial infection.
BOX 17-1 
DEFINITIONS OF POSITIVE TUBERCULIN SKIN TESTING[5]
Induration ≥5 mm

  Children in close contact with known or suspected contagious cases of tuberculosis
  Children suspected to have tuberculosis based on clinical or radiographic findings
  Children on immunosuppressive therapy or with immunosuppressive conditions (including HIV infection)
Induration ≥10 mm

  Children at increased risk for dissemination based on young age (<4 yr) or with other medical conditions (cancer, diabetes mellitus, chronic renal failure, or malnutrition)
  Children with increased exposure: those born in or whose parents were born in endemic countries; those with travel to endemic countries; those exposed to HIV-infected adults, homeless persons, illicit drug users, nursing home residents, incarcerated or institutionalized persons, migrant farm workers
Induration ≥15 mm

  Children ≥4 yr of age without any risk factors

TABLE 17-13   -- RECOMMENDED TREATMENT REGIMENS FOR DRUG-SUSCEPTIBLE TUBERCULOSIS IN INFANTS, CHILDREN, AND ADOLESCENTS
Infection or Disease CategoryRegimenRemarks
Latent tuberculosis infection (positive skin test, no disease)  
Isoniazid-susceptible9 mo of isoniazid q24 hrIf daily therapy is not possible, DOT twice a wk may be used for 9 mo.
Isoniazid-resistant6 mo of rifampin q24 hrIf daily therapy is not possible, DOT twice a wk may be used for 6 mo.
Isoniazid/rifampin- resistant[*]Consultation with a tuberculosis specialistFor management of neonates born to mothers with evidence of tuberculosis infection, see 2006 Red Book, pp. 694–695.[8]
Pulmonary and extrapulmonary (except meningitis)
  2 mo of isoniazid, rifampin, and pyrazinamide q24 hr, followed by 4 mo of isoniazid and rifampin by DOT
  9–12 mo of isoniazid and rifampin for drug-susceptible M. bovis
  If possible drug resistance is a concern, another drug (ethambutol or an aminoglycoside) is added to the initial 3-drug therapy until drug susceptibilities are determined. DOT is highly desirable.
  If hilar adenopathy only, a 6-mo course of isoniazid and rifampin is sufficient.
  Drugs can be given 2 or 3 times/wk under DOT in the initial phase if nonadherence is likely.
Meningitis
  2 mo of isoniazid, rifampin, pyrazinamide, and an aminoglycoside or ethionamide q24 hr, followed by 7–10 mo of isoniazid and rifampin q24 hr or twice per wk (9–12 mo total)
  At least 12 mo of therapy without pyrazinamide for drug-susceptible M. bovis
  A fourth drug, such as an aminoglycoside, is given with initial therapy until drug susceptibility is known.
  For patients who may have acquired tuberculosis in geographic areas where resistance to streptomycin is common, capreomycin(15– 30 mg/kg/day) or kanamycin (15–30 mg/kg/day) may be used instead of streptomycin.
Modified from Pickering LK (ed): 2006 Red Book: Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, Ill, American Academy of Pediatrics, 2006, p 686.
*Duration of therapy is longer in HIV-infected persons, and additional drugs may be indicated. DOT, directly observed therapy.


G.SELECTED TICK-BORNE ILLNESSES (Table 17-14)


TABLE 17-14   -- SELECTED TICK-BORNE ILLNESSES
DiseasePresentationTransmissionDiagnosisTreatment
Lyme disease
  (1) Early localized disease: 3-32 days after tick bite. Erythema migrans (annular rash at site of bite, target lesion with clear or necrotic center), fever, headache, myalgia, malaise.
  (2) Early disseminated disease: 3-10 wk after the tick bite. Secondary erythema migrans with multiple, smaller target lesions, cranioneuropathy (especially facial nerve palsy), systemic symptoms as previously listed, and lymphadenopathy; 1% may develop carditis with heart block or aseptic meningitis.
  (3) Late disease:Intermittent, recurrent symptoms occur 2-12 mo from initial tick bite. Pauciarticular arthritis affecting large joints (7% of those untreated), peripheral neuropathy, encephalopathy.
  SpirocheteBorrelia burgdorferi.Inoculation occurs by the bite of a deer tick,Ixodes scapularisor Ixodes pacificus;disseminates systemically through the blood and lymphatics.
  Transmission ofB. burgdorferirequires 24–48 hr of tick attachment.
  Occurs commonly in New England and the Middle Atlantic, Upper Midwest, and Pacific Northwest. April to October is the peak season.
  Clinical exam: Most cases of early Lyme disease can be diagnosed clinically by the characteristic erythema migrans rash or illness compatible with early or late disease (e.g., meningitis, facia palsy, arthritis)
  Laboratory markers:Immunoassays for B. burgdorferi-speciiicimmunoglobulin M (IgM), which begins at 3–4 wk and peaks at 6–8 wk after disease onset, and with S. ixjrgc/orfen-specific IgG, which rises wk to mo after symptoms appear and persists.
  False-positive results of these assays occur as result of cross-reactivity with viral infections, other spirochetal infections, and autoimmune diseases.
  Western blot assays should be used to confirm positive enzyme-linked immunosorbent assay (ELISA).
  Lyme disease-specific antibodies can be isolated from CSF in patients with CNS involvement.
Therapy depends on stage of disease. Antibiotic prophylaxis not routinely recommended for ticks attached <24–48 hr.
For early localized disease, doxycycline for 14–21 days is treatment of choice for patients >8 yr of age. Amoxicillin recommended for younger children. The following early disseminated and late-onset disease manifestations are treated by the same oral regimen as early disease, with treatment extended as indicated: multiple erythema migrans therapy for 21 days, isolated facial palsy treatment for 21–28 days, and arthritis treatment for 28 days.
Persistent or recurrent arthritis (>2 mo) and carditis may be treated with 14–21 days of ceftriaxone or 14–28 days of parenteral penicillin. Meningitis or encephalitis should be treated with ceftriaxone or parenteral penicillin for 14–28 days.
Rocky Mountain spotted fever
  Incubation period: 1–55 days.
  Fever, headache, and a characteristic rash that usually occurs by day 6 of illness; initially erythematous and macular and progresses to maculopapular and petechial. The rash usually appears on wrists and ankles and spreads proximally. Palms and soles are often involved. Other symptoms: Myalgia, nausea, anorexia, abdominal pain, diarrhea
  Laboratory manifestations:Thrombocytopenia, hyponatremia, and anemia White blood cell count usually normal
  Severe disease may manifest in CNS, cardiac, pulmonary, gastrointestinal tract, and renal involvement, disseminated intravascular involvement, and shock leading to death.
  Rickettsia rickettsii] an obligate intracellular pathogen transmitted to humans by a tick bite.
  Incidence highest between April and September. Most cases are reported in the south Atlantic, southeastern, and south central United States, although the disease is widespread in the United States and also occurs in Canada, Mexico, and Central and South America
  Diagnosis is by rickettsial group- specific s?rologie tests, which may be negative early in the illness. A fourfold or greater change between acute- and convalescent-phase serum specimens is diagnostic when determined by indirect immunofluorescence antibody (IFA) assay, enzyme immunoassay, or complement fixation, latex agglutination, indirect hemagglutination, or microagglutination tests.
  Probable diagnosis can be established by a single serum titer of 1: 64 or greater by IFA assay. Culture of R. rickettsii is generally not attempted because of danger of transmission to laboratory personnel. R. rickettsii can be obtained by immunohistochemica staining of tissue specimens obtained before initiation of antimicrobial therapy. This method is highly specific but not sensitive.
  Doxycycline is recommended drug for children of any age. Chloramphenicol is an alternative, although less favored because of serious side effects, the need to monitor levels, and lack of an oral preparation in the United States.
  Treatment initiated on the basis of clinical features and epidemiologic considerations. Usually lasts 7–10 days and is continued until the patient is afebrile for >3 days and has demonstrated clinica improvement.
Ehrlichiosis/anaplasmosis
  Caused by three distinct tick- borne pathogens: Ehrlichia chaffeensis (human monocytic ehrlichiosis, or H ME), Anaplasma phagocytophilum(human granulocytotrophic anaplasmosis, or HGA), and Ehrlichia ewingii.
  Systemic febrile illness with headache, chills, rigors, malaise, myalgia, arthralgia, nausea, vomiting, anorexia, or acute weight loss. Rash is variable in location and appearance.
  Laboratory manifestations:Leukopenia, anemia, and hepatitis are common.
  More severe disease:Pulmonary infiltrates, bone marrow hypoplasia, respiratory failure, encephalopathy, meningitis, disseminated intravascular coagulation, spontaneous hemorrhage, and rena failure.
  Ehrlichiainfections caused by HME and E. ewingii ateassociated with the bite of a lone star tick(Amblyomma americanum),although other tick species may be vectors. HGA is transmitted by the deer tick(Ixodes scapularis).
  Mammalian reservoirs for agents of human ehrlichiosis include white-tailed deer and white-footed mice.
  Most HME infections occur in the southeastern and south central United States. Most cases of HGA are reported from the north central and northeastern United States.
  Most human infections occur between April and September, with peak occurrence from May through July.
  Diagnosis confirmed by isolation of Ehrlichiaorganisms from blood or CSF, a fourfold or greater change in antibody titer by IFA assay between acute and convalescent serum specimens, PCR assay amplification of ehrlichial DNA from a clinical specimen, or detection of an intraleuko- cytoplasmic cluster of bacteria in conjunction with a single IFA titer >64.
  PCR from acute-phase periphera blood of patients with ehrlichiosis seems sensitive, specific, and promising for early diagnosis.
  Doxycycline is drug of choice, 4.4 mg/kg/day ql2 hr IV or PO (maximum, lOOmg/dose)
  Ehrlichiosis may be severe or fata in untreated patients; treatment should therefore be initiated early. Failure to respond within the first 3 days should suggest infection with an agent other than Ehrlichia spp. Treatment should be continued for at least 3 days after defervescence for a minimum total course of 5- 10 days.




TABLE 17-15   -- COMMON COMMUNITY-ACQUIRED FUNGAL INFECTIONS
DiseaseUsual EtiologySuggested TherapySuggested Length of Therapy
Tinea capitis (ringworm of scalp)Trichophyton tonsuransMicrosporum canisOral griseofulvin: Give with fatty foods. Fungal shedding decreased with1%– 2.5% selenium sulfide shampoo4–6 wk or 2 wk after clinical resolution
Alt: Terbinafine, itraconazole, or fluconazole
Tinea corporis/pedis (ringworm of body/feet)Trichophyton rubrumTrichophyton mentagrophytesMicrosporum canisTopical antifungal (miconazole, clotrimazole)4 wk
Terbinafine2 wk
Oral candidiasis (thrush)Candida albicansCandida tropicalisNystatin suspension or clotrimazole troches3 days after clinical resolution
Candidal skin infections (intertriginous)Candida albicansTopical nystatin, miconazole, clotrimazole3 days after clinical resolution
Tinea unguium (ringworm of nails)Trichophyton rubrumEpidermophyton floccosumOral terbinafine6 wk
Itraconazole3 mo
Fluconazole3–6 mo

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