tues commonly encountered outpatient infectious diseases ... · 10/1/18 5 uti-pathogenesis...
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Wind and WaterCommonly Encountered Outpatient
Infectious Diseases Diagnoses
Christine Cho MDUniversity of IowaInfectious Diseases
Disclosure
• Will be focusing on adult populations• No financial disclosure
Objectives
• Pneumonia– Define pathogenesis and diagnostic criteria– Understand the empiric treatment for pneumonia
• Urinary tract infection (UTI)– Define pathogenesis and diagnostic criteria – Understand the empiric treatment for UTI
Objectives
• Pneumonia– Define pathogenesis and diagnostic criteria– Understand the empiric treatment for pneumonia
• Urinary tract infection (UTI)– Define pathogenesis and diagnostic criteria – Understand the empiric treatment for UTI
Pneumonia
• Pathogenesis/Etiology• Diagnosis• Treatment
Pneumonia-Pathogenesis
• Defect in host defense + exposure to virulent microorganism + inoculum size
• Host defense: – Upper airways: nasopharynx, oropharynx– Conducting airways: trachea, bronchi– Lower respiratory tract: terminal airways, alveoli
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Pneumonia-EtiologyBacteria Virus Fungi OtherStreptococcus pneumoniae
Influenzae A/B Histoplasma capsulatum
Coxiella burnetii
Haemophilusinfluenzae
Respiratorysyncytial virus
Coccidioides immitis Rickettsiarickettsiae
Staphylococcus aureus
Human metapneumonvirus
Cryptococcus neoformans
Mycoplasma pneumoniae
Legionella spp. Adenovirus Aspergillus spp. Chlamydia pneumoniae
Enterobacteriaceae Rhinovirus Mycobacterium tuberculosis
Mixed anaerobic bacteria (aspiration)
NTM
Pneumonia-Diagnosis
• Clinical history: sudden onset fever, cough,
sputum production, shortness of breath,
physical findings of consolidation
• Lab/radiograph: leukocytosis, lung infiltrate
• Microbiology
– Sputum Gram’s stain and culture: 80% positive
with pneumococcal pneumonia (within 6-12h abx)
– Blood culture: 20-25% positive with
pneumococcal pneumonia
Musher et al. NEJM. 2014;371:1619-28.
Pneumonia-Diagnosis
• Pneumococcal urine antigen: – Sensitivity: 74%– Specificity: 97.2%
• Legionella urine antigen: Serotype 1– Sensitivity: 74%– Specificity: 99.1%
Prina et al. Lancet. 2015;386:1097-108.
Pneumonia-Pro-calcitonin
Procalcitonin level (µg/L) Bacterial Etiology Recommendation<0.1 Very unlikely Antibiotics strongly
discouraged
0.1-0.25 Unlikely Antibiotics discouraged
>0.25-0.5 Likely Antibiotics recommended
>0.5 Very likely Antibiotics stronglyrecommended
Huang et al. NEJM. 2018;379(3):236-249.
Procalcitonin Antibiotic Consensus Trial (ProACT)
• Procalcitonin group vs usual-care group
• US academic centers
• Primary outcome: Total # antibiotic-days within 30 days
Procalcitonin Usual-careRandomized 830 834
Primary outcome 826 830
Completed 30-day follow up
675 670
Antibiotic-days by day 30
4.2±5.8 4.3±5.6
Huang et al. NEJM. 2018;379(3):236-249.
Pneumonia-Diagnosis
• Radiology– Radiograph
• 75% for alveolar consolidation• 47% for pleural effusion
– CT: most accurate technique • Other diagnoses (pulmonary embolism)• Fungal lung infection• Unclear chest X-ray• Detection of complication (lung abscesses)
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Vilar et al. European Journal of Radiology. 2004;51:102-113.
Pneumonia-Diagnosis
• Disease severity– CURB-65: confusion, blood urea nitrogen,
respiratory rate, blood pressure, age>65– Pneumonia Severity Index: demographic, co-
existing illness, physical exam finding, lab/radiographic finding
Pneumonia-Diagnosis
Prina et al. Lancet. 2015;386:1097-108.
Pneumonia-Treatment• Empiric treatment (IDSA/ATS guideline, 2007)
Preferred AlternativeOutpatient withoutcomorbidities; low severity
Macrolide Doxycycline
Outpatient with comorbidities or high rate of bacterial resistance
β-lactam + macrolide
Respiratory fluoroquinolone
Inpatient not in ICU; moderate severity
β-lactam + macrolide
Respiratory fluoroquinolone
Inpatient in ICU; high severity
β-lactam + macrolide
β-lactam + respiratoryfluoroquinolone
Mandell et al. Clin Infect Dis. 2007;44 (suppl 2): S27-72.
Antibiotics
• Macrolides– QT interval prolongation– Resistance development (especially S. pneumoniae)
• Fluoroquinolones– C.difficile infection– CNS effect: delirium, agitation, memory impairment– Peripheral neuropathy– Tendinopathy– QT interval prolongation
β-lactam monotherapy vs β-lactam+macrolide
• Randomized noninferiority trial• Moderately severe community-acquired pneumonia• Primary outcome:
– did not reach clinical stability by day-7
• Did not find non-inferiority of monotherapy (upper limit of the 1-sided 90% CI=13%; 8% boundary)
Randomized Completed follow up
Primary outcome
β-lactam monotherapy
300 291 120 (41.2%)
β-lactam +macrolide
302 289 97 (33.6%)
Garin et al. JAMA Intern Med. 2014;174(12):1894-1901.
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Community-Acquired Pneumonia-Study on the Initial Treatment with Antibiotics of Lower Respiratory Tract
Infections (CAP-START) Trial
• Randomized, cross over trial• Noninferiority: – β-lactam (BLM) monotherapy – β-lactam+macrolide– Fluoroquinolone (FQ) monotherapy
• Primary outcome: all-cause mortality within 90 days after admission
Postma et al. NEJM. 2015;372:1312-23.
CAP-START Trial
BLMmonotherapy BLM+Macrolide FQEnrolled 656 739 888
Adherence 93% 88% 92.7%
Crude 90-day Mortality
9% 11.1% 8.8%
• “BLM monotherapy was non-inferior to strategies with a BLM+macrolide combination or FQ monotherapy with regard to 90-day mortality”
Postma et al. NEJM. 2015;372:1312-23.
Pneumonia-Treatment Duration
• Duration of antibiotic treatment in Community-Acquired Pneumonia
• Multicenter randomized clinical trial• IDSA/ATS duration: 5 days (minimum),
achieving afebrile state for 48-72 hours and meeting no more than 1 CAP-associated instability criteria
Uranga et al. JAMA Int Med. 2016;176(9):1257-1265.
• Determined by physician (medial: 10-day) vs 5-day (Intervention)
• Outcome: resolution/improvement in sign/symptoms of pneumonia + CAP symptom questionnaire
Pneumonia-Treatment Duration
Control Intervention p-valueenrolled 150 16210-dayFollow up
71 (48.6%) 90 (56.3%) 0.18
30-dayFollow up
132 (88.6%) 147 (91.9%) 0.33
“withdrawing antibiotic treatment based on clinical stability criteria after a minimum of 5 days of appropriate treatment is not inferior to traditional treatment schedules in terms of clinical success”
Uranga et al. JAMA Int Med. 2016;176(9):1257-1265.
Niederman M.S. Annals of Internal Medicine. 2015;163(7):ITC1.DOI: 10.7326/AITC201510050
Objectives
• Pneumonia– Define pathogenesis and diagnostic criteria– Understand the empiric treatment for pneumonia
• Urinary tract infection (UTI)– Define pathogenesis and diagnostic criteria – Understand the empiric treatment for UTI
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UTI-Pathogenesis
Flores-Mireles et al. Nature Reviews-Microbiology. 2015;13:269-284.
Cystitis
Pyelonephritis
UTI-Epidemiology
Flores-Mireles et al. Nature Reviews-Microbiology. 2015;13:269-284.
UTI-Definition
• Uncomplicated: No structural abnormality• Complicated– Defect in host defense– Structural compromise
UTI-Diagnosis
• Symptoms: fever, flank/abdominal pain, dysuria, urinary urgency, hematuria
• Pyuria: Urine dipstick
– >10 WBC/mm3: sens=75-96%, spec=94-98%
– Pyuria ≠ UTI
• Positive urine culture:
– Cystitis > 103 colony-forming units (CFU)/mL of a uropathogen (sens=90%, spec=90%)
– Pyelonephritis > 104 CFU/ml (sens=90%, spec=90%)
UTI treatment in women
• Asymptomatic bacteriuria
– General population ~ 5%
– Women > 70: 15-17% (30-
50%)
• Chronic GU symptoms:
urinary frequency and
urgency
• Medications: diuretics
Mody et al. JAMA. 2014;311(8):844-854.
UTI in Older Women-Diagnosis
Mody et al. JAMA. 2014;311(8):844-854.Bent et al. JAMA. 2002;287(20):2701-2710.
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UTI-TreatmentAntimicrobial Mechanism of
ActionPharmacokinetics Pharmacodynamics
Nitrofurantoin Complex; inactivates/alters bacterial ribosomal proteins and other macromoleculesàDNAdamage
90% renal elimination (30-40% unchanged)
Bactericidal or static (concentration-dependent)
TMP/SMX Sequentially inhibits steps in bacterial folate synthesis
Renal elimination (mostly unchanged); renal dose adj CrCl<30
Bactericidal
Fosfomycin Binds/inhibits MurA(early stages of peptidoglycan synthesis)
38% renal elimination (unchanged); no dosage adj in renal impairment or elderly population
Bactericidal
Fluoroquinolones DNA gyrase and topoisomerase inhibitor (DNA synthesis)
Renal elimination; dose adj in renal impairment
Bactericidal
β-lactam Inhibit peptidoglycan synthesis
Renal elimination; dose adj in renal impairment
Bactericidal
Walker et al. Clinical Infectious Diseases. 2016;63:960-965.
Uncomplicated Cystitis-Treatment
• IDSA/ESMID 2010 update
• Rule out pyelonephritis (fever, flank pain)
• Nitrofurantoin 100mg BID x 5d, TMP/SMX DS BID x 3d, fosfomycin 3g single dose
• Fluoroquinolones x 3d
• β-lactam (amox/clauv, cefdinir, cefaclor, cefpodoxime-proxetil) x 3-7d– Ampicillin or amoxicillin have poor efficacy
Gupta et al. Clinical Infectious Diseases. 2011;52(5):e103-e120.
Acute Pyelonephritis-Treatment
• Urine culture with susceptibility• Ciprofloxacin 500mg BID x 7d– Not requiring hospitalization– Community resistance < 10%
• TMP/SMX DS BID x 14d– Not requiring hospitalization
Gupta et al. Clinical Infectious Diseases. 2011;52(5):e103-e120.
Antibiotics
• Nitrofurantoin– Not indicated for pyelonephritis– Nausea/vomiting, Pulmonary Reactions
• Fosfomycin– Not indicated for pyelonephritis– Diarrhea and headache
Mody et al. JAMA. 2014;311(8):844-854.
Fosfomycin vs Ibuprofen
• Uncomplicated cystitis in women• Fosfomycin 3g once vs Ibuprofen x 3 days• Primary outcome: – Total number of courses of antibiotics on days 0-
28– Burden of symptoms on days 0-7 (Daily symptoms
scores)
Gagyor et al. BMJ. 2015;351:h6544.
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Fosfomycin vs Ibuprofen
• “We have to reject the hypothesis of non-inferiority of initial symptomatic treatment, and we cannot generally recommend the ibuprofen first approach. This treatment option, however, can be discussed with women with mild to moderate symptoms in a shared decision making approach…”
Gagyor et al. BMJ. 2015;351:h6544.
Ibuprofen (n=241)
Fosfomycin(n=243)
% mean difference (95% CI)
P value
Received Abxduring f/u
75 (31%) 30 (12%) 18.8(11.6-25.9)
<0.001
Take Home Points-Pneumonia
• Pathogen: S. pneumoniae, H. influenzae, atypical (M. pneumoniae, C. pneumoniae, L. pneumophila), virus
• Diagnosis: Clinical history– Culture: useful if appropriately collected– Lab: procalcitonin is useful to rule out pneumonia
• Treatment: macrolide à β-lactam+macrolide
Take Home Points-UTI• E. coli is the most common pathogen• Diagnosis: – Clinical history: dysuria, back/flank pain– Pyuria ≠ UTI– Asymptomatic bacteruria ≠ UTI
• Treatment: – Cystitis: nitrofurantoin, TMP/SMX, fosfomycin,
fluoroquinolone, β-lactam (except ampicillin/amoxicillin)
– Pyelonephritis: ciprofloxacin, TMP/SMX
Questions?