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재진 아
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1 감염내과에흔히의뢰하는질문들 서울대학교의과대학내과학교실분당서울대학교병원감염내과김홍빈

2 VDRL 양성 다룰내용들 감별진단, 치료, 추적관찰 요로감염증 다제내성균방광염의치료 무증상세균뇨 경부림프절병 ( 증 ) 예방접종 PCV13 versus PPSV23

3 증례 : 흔한질문 증례 1 증례 2 OO 수술예정인환자로수술전검사에서 VDRL 양성으로나와의뢰드리오니고진선처앙망하나이다. 병실에서채혈하는도중 ( 혹은수술중 ) 바늘에찔렸습니다. 환자는 VDRL 양성입니다. 어떻게해야합니까?

4 William Osler, 매독 father of modern medicine He who knows syphilis, knows medicine. Syphilis is no respecter of age, sex, or station in life. Great imitator

5 반짝이는모든것이 금 은아니다 VDRL (+) Syphilis??

6 Causes of False-Positive Serologic Tests Nontreponemal causes Acute condition(<6 months) Chronic condition(>6 months) Pneumonia Chickenpox Liver disease Viral HIV infection Malignancy Pneumococcal Virus infection Intravenous drug use Mycoplasma Measles Aging Hepatitis Malaria Connective tissue disorders Tuberculosis Immunizations Multiple blood transfusions Mononucleosis Preganancy Chancroid Laboratory error Treponemal causes Acute condition(<6 months) Mononucleosis Leprosy Chronic condition(>6 months) Systemic lupus erythematosus Lyme disease Malaria

7 Sensitivity and Specificity of Diagnostic Tests Test % Sensitivity at given stage of infection Primary Secondary Latent Late % Specificity (nonsyphilis) VDRL 78 (74-87) (88-100) 71 (37-94) 98 (96-99) MHA-TP 76 (69-90) (97-100) (98-100) FTA-ABS 84 (70-100) (94-100)

8 % Positivity of Serologic Tests

9 Natural History of Untreated Syphilis Exposure Primary Incubation Days From Exposure Infectious Via Sexual or Mother-to to-child Transmission Primary Syphilis (Chancre Formation) Secondary Incubation (4-10 Weeks After Appearance of Chancre) Central Nervous System Invasion 25%-60% Early Neurosyphilis Asymptomatic Symptomatic 5% Infectious via Mother-to to-child Transmission Recurrence Secondary Syphilis 24 % Early Latent Syphilis (Asymptomatic) (1 Year or Less Postinfection) Late Latent Syphilis (Asymptomatic) (1 Year or more Postinfection) Meningitis Cranial Neurtis Ocular Involvement Meningovascular Disease Noninfectious Tertiary Syphilis Cardiovascular Syphilis Gummatous Disease 10% 15% (Onset Years (Onset Years Postinfection) Postinfection) Tertiary Syphilis Late Neurosyphilis General Paresis Tabes Dorsalis 2% - 5% 2% - 9% (Onset Years (Onset Years Postinfection) Postinfection)

10 Common Presentations in the Different Stages of Syphilis Stage Primary Secondary Latent Tertiary Presentation Painless ulcer at of inoculation Regional lymphadenopathy Rash, especially on the palms and soles Mucous membrane lesions Malaise, fever, sore throat, headache, arthralgia, generalized lymphadenopathy Syphllitic meningitis with cranial nerve palsies, iritis with anterior uveitis Asymptomatic, detectable by abnormal serologic test results Cardiovascular syphilis aortic aneurysm, aortic regurgitation, nonatherosclerotic coronary artery disease Gummatous syphilis Neurosyphilis Asymptomatic neurosyphilis Tabes dorsalis: lightning pains, pupillary abnormalities, ataxia, lower extremity reflex abnormalities, incontinence General paresis: dementia with slurred speech, pupillary abnormalities, reflex abnormalities, tremor seizures

11 Classification of Syphilis Early infectious syphilis Primary syphilis An often painless anogeniyal chancre(ulcer) with dependent lymphadenopathy Can persist into the secondary stage Incubation period of 9-90d but usually 3-4 wks Secondary syphilis Multisystem involvement due to bacteraemia, resulting in generalised rash (+/- condylomata lata), and lymphadenopathy, systemic malaise and fever, buccal and genital mucosal erosions; may also cause patchy alopecia, hepatitis, meningitis, cranial nerve palsies,uveitis, periostitis and glomerulonephritis 4-8 wks after appearance of chancre Early latent syphilis Late non-infectious syphilis Late latent syphilis Gummatous syphilis Neurosyphilis Cardiovascular syphilis From the end of the secondary stage to the end of a 1yr period after the appearance of chancre Positive serologic tests for syphilis but without symptoms or signs Classifled as infectious because relapse to the secondary stage is possible up to 1yr From the 1y point onwards Asymptomatic with positive serologic tests for syphilis Most untreated patients would remain in this stage Rare but described in patients recently co-infected with HIV; can be infiltrative or ulcerative Rare but rapid progress to this stage, described in patients co-infected with HIV; meningovascular, tabes dorsalis and general paresis Rare; aortic regurgitation or aneurysm, coronary ostiitis

12 Early vs. late latent syphilis A documented seroconversion Unequivocal symptoms of primary or secondary syphilis A sex partner documented to have primary, secondary, or early latent syphilis Nontreponemal titer??

13 Approximate time course of the clinical manifestations of early syphilis and neurosyphilis Personality Affect Reflexes Eye Sensorium Intellect Speech (N Engl J Med 326:1060-9, 1992)

14 매독의치료 항생제의종류 Benzathine penicillin G T. pallidum doubling time > hrs Aqueous penicillin G Doxycycline Ceftriaxone Azithromycin CDC s recommended Tx Clinical experience >> controlled trial

15 Management of Sex Partners At-risk partners 3 months + duration of symptoms for primary 6 months + duration of symptoms for secondary 1 year for early latent syphilis Management Before the diagnosis of primary, secondary, or early latent syphilis within 90 days : presumptive treatment even if seronegative > 90 days : based on serologic test results Latent syphilis : long-term partners - based on clinical & serologic evaluation

16 매독혈청검사양성 전염?? 매독이옮을가능성페니실린부작용이생길가능성 * 주사침에묻어있는혈액을통해매독균이옮을가능성은거의없음. 특별한예방조치는필요없음

17 50/ 여자 증례 3: 치료후경과관찰 Late latent syphilis Tx with benzathine penicillin IM (X3) VDRL titer F/U 1:4 ( ), 1:4 ( ), 1:2 ( ) No symptoms or signs at

18 Follow-up Clinical & Serologic F/U 6, 12 and 24 months after treatment 3, 6, 9, 12 and 24 months in HIV (+) Treatment failure Persistent or recurring signs or symptoms 4-fold (2 dilutions) decrease (-) within 6 months Sustained 4-fold increase after treatment HIV test & CSF analysis Serofast reaction : life-long positive low titer VDRL

19 요약 매독환자 : Anti-HIV 검사추천 ( 잠복매독??) 잠복매독 전염성이없다. 치료의목적은후기합병증의발생이나진행을막기위한것이다. 매독의치료 : 페니실린이으뜸 Nontreponemal test (VDRL) : 치료후에도양성일수있다.(serofast 포함 )

20 50 세여자 증상과징후 증례 4 3 일전시작한배뇨곤란, 빈뇨, 야간배뇨를주소로방문발열, 오심, 구토는없음 치골상부압통이있고늑골척추각압통은없음 요검사결과백혈구수가 many/hpf 요배양검사결과 Escherichia coli > 10 5 /ml

21 소변배양 : E. coli > 10 5 /ml Ampicillin R Imipenem S Cefazolin R Gentamicin R Cefotaxime R Tobramycin R Ceftazidime R Amikacin S Cefuroxime R Ciprofloxacin R Aztreonam R Trimethoprim S /sulfamethoxazole ESBL (+) 광범위베타락탐분해효소생성균주 (extended spectrum beta-lactamase, ESBL-producer)

22 치료는? 1) Cefixime 400mg po qd 2) Ciprofloxacin 250mg po q 12hr 3) Ertapenem 1gm iv q 12hr 4) Fosfomycin 3gm po (single dose) 5) Imipenem 500mg iv q 6hr 6) Meropenem 1gm iv q 8hr 7) Trimethoprim-sulfamethoxazole 2T po q 12hr

23 Pharmacokinetic characteristics

24 Clinical Guidelines for Acute Uncomplicated Cystitis in Women Recommended antibiotics Alternative antibiotics KSID/KSAC/KAUTI/KSCM (2011) Fluoroquinolone x 3 d (A-I) Fosfomycin (B-I) Nitrofurantoin (B-I) Cefpodoxime, cefixime (B-II) Amox/clav (C-I) Considerations High resistance rate in E. coli (TMP/SMX 29-39%, ciprofloxacin 14-23%) IDSA/ESCMID (2011) Nitrofurantoin x5 d (A-I) TMP/SMX x3 d, in case of resistance 20% (A-I) Fosfomycin, single dose (A-I) Pivmecillinam x3-7 d (A-I) Fluoroquinolones (A-I) β-lactams (B-I) Propensity for collateral damage: fluoroquinolones and β-lactams KSID: 대한감염학회, KSAC: 대한화학요법학회, KAUTI: 대한요로생식기감염학회, KSCM: 대한임상미생물학회, IDSA: 미국감염학회, ESCMID: 유럽임상미생물감염학회

25 증례 5 62 세여자, 방광염치료의병력이있음 증상이나징후 발열, 요절박 ( 소변못참음 ), 배뇨통등의증상없음 치골위압통이나늑골척추각압통없음 요검사 : 백혈구수 > 100/HPF 요배양검사 : Escherichia coli > 10 5 /ml

26 무증상세균뇨 검사및치료?? 어떤경우에바람직한것인가? Asymptomatic bacteriuria adverse outcome Intervention of screeing & antimicrobial Tx improvement of outcome

27 무증상세균뇨의유병률

28 다음중적절한경우는?? Premenopausal, non-pregnant women Pregnant women Diabetic women (NEJM 2002;347: ) Older persons residing in the community Elderly institutionalized subjects Subjects with spinal cord injuries Patients with indwelling urethral catheters Urologic interventions Immuno-compromised patients

29 IDSA guidelines (CID 2005;40:643-54) Pregnant women Traumatic urologic interventions with mucosal bleeding [ex. TUR-B]

30 증례 6 24 세여자 2 주전부터만져진목부위의종괴, 약간의통증이있지만크기변화없음 하지만, 동반된전신증상없음 Multiple, 1-2cm, sl. tender, soft, movable, both cervical LNs 과거결핵병력 (-)

31 나이에따른경부종괴의감별 빈도 0~15세 16~40세 >40세 흔함 염증질환 염증질환 악성종양 선천질환 선천질환 염증질환 악성종양 악성종양 선천질환 드묾 외상 외상 외상 (Cummings CW, et al. Otolaryngology-Head and Neck surgery, 2005)

32 조직검사가급한경우 임상적으로악성종양의심 : 고령의흡연자, 압통이없고딱딱하며단일림프절병증 악성림프종의심 : 단단하고 (firm, rubbery), 유착되지않은 (movable) 단일혹은전신림프절병증 쇄골상부림프절 (SCN) 의림프절병증 림프절병증이 3-4주이상지속되면서전신증상 ( 발열, 야간발한, 체중감소등 ) 이동반될때

33 조직검사전추적관찰기간 국소림프절병증일경우 악성종양의위험성이없을경우 2~4주정도추적관찰가능 비교적안전하고불필요한검사를피할수있음 관찰기간중증상, 징후가더명확해질수있음 자가진단에대해교육필요 ( 크기증가등 ) 세균감염이라는증거가없다면항생제투여제한 스테로이드투여는추후진단을어렵게할수있음

34 국내경부림프절병증의특성 총 147 명 (M:F, 41:106), 중심부침생검시행 137 명 (93.2%) 에서원인질환진단 2% 1% 4% 3% 19% 10% 24% 37% Kikuchi병결핵비특이림프절염악성종양 Kimura병세균성림프절염전신홍반루푸스기타 (Song JY, et al. J Infect 2007;55:310)

35 국내경부림프절염 특성 Kikuchi 병 (51명) 결핵 (33명) 비특이 (33명) 연령 ( 중간값 )* 27.8세 37.3세 29.6세 림프절크기 * 14.2 ± 7.5 mm 22.5 ± 13.5 mm 14.9 ± 6.8 mm 여러개침범 * 86.3% 48.5% 81.8% 뭉침 * 34.1% 37.5% 7.4% 압통 78.4% 78.8% 75.8% 단단함 * 0.8% 30.3% 6.1% 유착 * 3.9% 30.3% 0% 발열 68.6% 54.5% 60.6% 백혈구 * 4,038 ± 1,435/uL 6,582 ± 2,149/uL 6,022 ± 1,985/uL 혈소판 * 202 ± 50K/uL 282 ± 65K/uL 237 ± 95K/uL ESR* 33.3 ± ± ± 12.9 CPA 결핵소견 * 4/49 16/30 4/31 * 통계적으로유의한차이를보인항목 (Song JY, et al. J Infect 2007;55:310)

36 경부림프절병증의접근방법 병력, 신체진찰 원인진단 치료 원인미상 전신림프절병증 국소림프절병증 혈액검사, chest PA 악성종양가능성 (+)* 악성종양가능성 (-) 원인진단 원인미상 2-4 주경과관찰 자문 자문 호전없음 호전 조직검사 조직검사 경과관찰 * 나이 >40 세 ( 흡연자 ); >2.5 cm 2 ; 딱딱함 / 단단함 ; 쇄골상부림프절 ; 최근 ENT 증상 (-); 압통 (-)

37 68 세남자 증례 7 만성신부전으로약복용중 보건소에무료폐렴구균예방접종받으러갔더니다니던병원에가서상의하랍니다! 3-4 년전폐렴구균예방접종을받은기억이나는데

39 폐렴사슬알균백신적응증 65세이상의모든성인 65세미만의성인중다음의기저질환이있는경우 만성폐쇄성폐질환, 폐기종, 천식 만성심질환 ( 단순고혈압제외 ), 당뇨 만성간질환, 알코올중독 만성신부전, 신증후군 (nephrotic syndrome) 인공와우이식, 뇌척수액누수 (CSF leak) 기능성 / 해부학적무비증 면역억제환자 ( 고형암, 혈액암, 면역억제제복용중인자등 ) 요양기관에거주중인경우 흡연자

40 Risk group Underlying medical condition PCV13 PPSV23 Revaccination 5yrs after 1 st Immunocompetent persons Chronic heart/lung/liver disease, Diabetes, Alcoholism, Smoking Cerebrospinal fluid leak Cochlear implant Persons with functional Sickle cell diseases/other Hbinopathy or anatomic asplenia Congenital or acquired asplenia dose Immunocompromised persons Congenital or acquired immunodeficiency HIV infection Chronic renal failure Nephrotic syndrome Leukemia/Lymphoma Multiple myeloma Generalized malignancy Iatrogenic immunosuppression Solid organ transplant Modified from Recommendation of Advisory Committee on Immunization Practices, United States, 2012

41 PPSV23 & PCV13 투약순서 - 간격 폐렴사슬알균예방접종력없음. >8주 >5년 PCV13 PPSV23 PPSV23 PPSV23 으로예방접종을받았던사람. >1년 PCV13 PPSV23 PPSV23 >5년

42 대한감염학회 (

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<B0E6C8F1B4EBB3BBB0FA20C0D3BBF3B0ADC1C E687770> 2012 개원의와함께하는임상강좌 경희대학교의과대학감염내과학교실 문수연 F/29 CC: fever, headache, multiple cervical lymph node onset) 5 days ago 1 cm sized Bilateral, mild tender, movable, soft Reactive LN with viral infection 2012 개원의와함께하는임상강좌