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Treatment of MDR Gram-negative bacilli

f3b5d87da5acf2c8d79ff55edb954115_MD5.jpeg

Green, susceptibility anticipated to be >80%; yellow, susceptibility anticipated to be 30% to 80%; red, intrinsic resistance or susceptibility anticipated to be <30%.
1, US Food and Drug Administration–approved agent; 2, synthetic tetracycline derivative; 3, imipenem-cilastatin–relebactam; 4, synthetic aminoglycoside; 5, polymyxin class.
Abbreviations: KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase. (Tamma et al., 2024)

Treatment of MDR Gram-negative bacilli

f3b5d87da5acf2c8d79ff55edb954115_MD5.jpeg

Green, susceptibility anticipated to be >80%; yellow, susceptibility anticipated to be 30% to 80%; red, intrinsic resistance or susceptibility anticipated to be <30%.
1, US Food and Drug Administration–approved agent; 2, synthetic tetracycline derivative; 3, imipenem-cilastatin–relebactam; 4, synthetic aminoglycoside; 5, polymyxin class.
Abbreviations: KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase. (Tamma et al., 2024)

Lung ultrasound

LUS Finding Description Clinical Significance
A-lines Horizontal, repetitive lines Normal lung aeration or pneumothorax
B-lines Vertical, hyperechoic laser-like artifacts Pulmonary edema, pneumonia, ILD, ARDS
Consolidation Tissue-like hypoechoic region Pneumonia, atelectasis, infarction
Pleural Effusion Anechoic or echogenic fluid collection Heart failure, infection, malignancy
Lung Sliding Pleural shimmering movement Absent in pneumothorax or adhesions
Shred Sign Irregular lung border Pneumonia-related consolidation
Lung Point Transition between sliding and no sliding Pneumothorax
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DM

American Diabetes Association Professional Practice Committee, ElSayed, N.A., Aleppo, G., Bannuru, R.R., Beverly, E.A., et al. (2024) Summary of Revisions: Standards of Care in Diabetes—2024. Diabetes Care. 47 (Supplement_1), S5–S10. doi:10.2337/dc24-SREV.

Diagnosis

Criteria for the diagnosis of diabetes in nonpregnant individuals 1

  • A1C ≥6.5% (≥48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.2 OR
  • Fasting plasma glucose (FPG) ≥126 mg/dL (≥7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.2 OR
  • 2-h plasma glucose ≥200 mg/dL (≥11.1 mmol/L) during oral glucose tolerance test. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.2 OR
  • In an individual with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (≥11.1 mmol/L). Random is any time of the day without regard to time since previous meal.

Treatment of CRAB

Source

  • The use of high-dose ampicillin-sulbactam (total daily dose of 6–9 g of the sulbactam component) in combination with at least 1 other agent is suggested for the treatment of CRAB infections.

Key Opportunities to Improve Antibiotic Use

Source

狀況 診斷考量 經驗治療 根據培養結果調整最終療法並確定治療時長，包括出院處方
社區性肺炎 治療開始後複查病例以確認肺炎診斷或排除非感染性病因。 除非有臨床指徵，避免經驗性使用抗綠膿桿菌β-lactam類藥物和/或抗MRSA藥物。 大多數無併發症的成年肺炎病例可在患者迅速臨床反應的情況下進行5天治療。數據也顯示，MRSA鼻腔移生檢測結果為陰性可幫助指導停用MRSA肺炎的經驗性治療
泌尿道感染 實施尿液培養開立標準，以確保陽性培養更可能代表感染而非膀胱移生。例如：
僅在患者出現符合UTI的徵兆和症狀時訂開立培養，如尿急、頻尿、排尿困難、耻骨上疼痛、側腹疼痛、骨盆不適或急性血尿。
對於使用導尿管的患者，若無UTI的徵兆和症狀，避免僅因尿液外觀混濁或氣味難聞而進行尿液培養。
譫妄、噁心和嘔吐等非特異性徵兆和症狀應謹慎解讀，因為單獨這些徵兆對UTI的特異性較低。		 建立標準以區分無症狀和有症狀的菌尿症。除非在某些臨床情況下需要治療（如妊娠婦女和進行侵入性泌尿生殖手術的患者），否則應避免對無症狀菌尿症進行抗生素治療。 使用臨床適宜的最短抗生素治療時長。
皮膚和軟組織感染 制定診斷標準以區分化膿性和非化膿性感染，以及疾病的嚴重程度（即輕度、中度和重度），以便根據指南適當管理皮膚和軟組織感染。 除非有臨床指徵，避免經驗性使用抗綠膿桿菌β-lactam類藥物和/或抗厭氧菌藥物。對於無併發症的非化膿性蜂窩織炎，可能不需要使用特別針對MRSA的治療。 大多數無併發症的細菌性蜂窩織炎病例可在患者迅速臨床反應的情況下進行5天治療。
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Urinary tract infection

source: Pocket Medicine, 2022
UTI_zh

Definitions

  • Asymptomatic bacteriuria: presence of bacteria in urine without signs or symptoms of infection
  • Uncomplicated: confined to bladder. No upper tract or systemic infection signs.
  • Complicated:
    • extends beyond bladder (pyelonephritis, renal/perinephric abscess, prostatitis) with symptoms of fever, rigors, malaise, flank pain, CVA tenderness or pelvic/perineal pain.
    • More likely to develop bacteremia or sepsis.
    • Men, those w/ nephrolithiasis, strictures, stents, urinary diversions, immunosupp, DM, are not automatically complicated.
    • Pregnant & renal transplant are considered complicated.
  • in medicine
  • 3 min read

Sepsis and Shock

source: Pocket Medicine, 2022

Shock

  • Tissue hypoxia due to ↓ tissue perfusion and hence ↓ tissue O2 delivery and/or ↑ O2 consumption or inadequate O2 utilization
  • Typical signs include HoTN (SBP <90 mmHg or drop in SBP >40 mmHg), tachycardia, oliguria (UOP <0.5 cc/kg/h), Δ mentation, metabolic acidosis ± ↑ lactate
  • Hard to diagnose as ↑ SVR can maintain SBP, but tissue perfusion poor; shock index (HR/SBP) >0.9 and pulse pressure [(SBP - DBP)/SBP] <25% clues to significant shock
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  • 15 min read

BACTEREMIA

Definitions

  • Primary bacteremia: bloodstream infection due to direct inoculation of the blood
  • Central line associated bloodstream infection (CLABSI): bacteremia in which the same organism is growing from peripheral and catheter cultures (CID 2009;49:1)
  • Secondary bacteremia: infection of another site (eg, UTI, pneumonia, colitis, etc.) spreading to blood
  • Contaminant: bacteria growing in a blood culture that does not represent a true infection
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  • 5 min read

Invasive Mold Disease

Source: [@Donnell2020RevisionUpdate]

  • Proven IFD can apply to any patient, regardless of whether the patient is immunocompromised
  • Probable invasive fungal diseases (IFD) requires the presence of at least 1 host factor, a clinical feature and mycologic evidence and is proposed for immunocompromised patients only
  • Cases that meet the criteria for a host factor and a clinical feature but for which mycological evidence has not been found are considered possible IFD
  • (1,3)-beta-D glucan was not considered to provide mycological evidence of any invasive mold disease

Proven

  • Microscopic (Sterile Material): Histopathologic, cytopathologic, or direct microscopic examinationb of a specimen obtained by needle aspiration or biopsy in which hyphae or melanized yeast-like forms are seen accompanied by evidence of associated tissue damage
  • Culture (Sterile Material): Recovery of a hyaline or pigmented mold by culture of a specimen obtained by a sterile procedure from a normally sterile and clinically or radiologically abnormal site consistent with an infectious disease process, excluding BAL fluid, a paranasal or mastoid sinus cavity specimen, and urine
  • Blood: Blood culture that yields a mold (eg, Fusarium species) in the context of a compatible infectious disease process
  • Tissue Nucleic Acid Diagnosis: Amplification of fungal DNA by PCR combined with DNA sequencing when molds are seen in formalin-fixed paraffin-embedded tissue

Probable

Host factors

  • Recent history of neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3] for >10 days) temporally related to the onset of invasive fungal disease
  • Hematologic malignancy1
  • Receipt of an allogeneic stem cell transplant
  • Receipt of a solid organ transplant
  • Prolonged use of corticosteroids (excluding among patients with allergic bronchopulmonary aspergillosis) at a therapeutic dose of ≥0.3 mg/kg corticosteroids for ≥3 weeks in the past 60 days
  • Treatment with other recognized T-cell immunosuppressants, such as calcineurin inhibitors, tumor necrosis factor-a blockers, lymphocytespecific monoclonal antibodies, immunosuppressive nucleoside analogues during the past 90 days
  • Treatment with recognized B-cell immunosuppressants, such as Bruton’s tyrosine kinase inhibitors, eg, ibrutinib
  • Inherited severe immunodeficiency (such as chronic granulomatous disease, STAT 3 deficiency, or severe combined immunodeficiency)
  • Acute graft-versus-host disease grade III or IV involving the gut, lungs, or liver that is refractory to first-line treatment with steroids
ICU patients [@Bassett2021EORTCMSGERC]
  • Glucocorticoid treatment with prednisone equivalent of 20 mg or more per day
  • Qualitative or quantitative neutrophil abnormality (inherited neutrophil deficiency, absolute neutrophil count of ≤500 cells/mm3)
  • Chronic respiratory airway abnormality (chronic obstructive lung disease, bronchiectasis)
  • Decompensated cirrhosis
  • Treatment with recognized immunosuppressants (eg, calcineurin or mammalian target of rapamycin [mTOR] inhibitors, blockers of tumor necrosis factor [TNF] and similar antifungal immunity pathways, alemtuzumab, ibrutinib, nucleoside analogues) during the past 90 days
  • Hematological malignancies/HSCT
  • SOT
  • Human immunodeficiency virus infection
  • Severe influenza (or other severe viral pneumonia, such as coronavirus disease 2019)
COVID-19 Associated Pulmonary Aspergillosis (CAPA) [@Koehler2021Definingmanaging]
  • Positive SARS-CoV-2 RT-PCR anytime during 2 weeks between hospital admission and ICU admission or positive RT-PCR within 72–96 h after ICU admission
  • Respiratory insufficiency requiring intensive care

Clinical features

Pulmonary aspergillosis
  • The presence of 1 of the following 4 patterns on CT:
    • Dense, well-circumscribed lesions(s) with or without a halo sign
    • Air crescent sign
    • Cavity
    • Wedge-shaped and segmental or lobar consolidation
CAPA
  • Pulmonary infiltrate (chest CT) or cavitating infiltrate (not attributed to another cause)
Other pulmonary mold diseases
  • As for pulmonary aspergillosis but also including a reverse halo sign
Tracheobronchitis
  • Tracheobronchial ulceration, nodule, pseudomembrane, plaque, or eschar seen on bronchoscopic analysis
Sino-nasal diseases
  • Acute localized pain (including pain radiating to the eye)
  • Nasal ulcer with black eschar
  • Extension from the paranasal sinus across bony barriers, including into the orbit
Central nervous system infection

1 of the following 2 signs:
- Focal lesions on imaging
- Meningeal enhancement on magnetic resonance imaging or CT

Mycology evidences

  • Any mold, for example, Aspergillus, Fusarium, Scedosporium species or Mucorales recovered by culture from sputum, BAL, bronchial brush, or aspirate
  • Microscopical detection of fungal elements in sputum, BAL, bronchial brush, or aspirate indicating a mold
Tracheobronchitis
  • Aspergillus recovered by culture of BAL or bronchial brush
  • Microscopic detection of fungal elements in BAL or bronchial brush indicating a mold
CAPA: At least one of the following
  • Microscopic detection of fungal elements in bronchoalveolar lavage, indicating a mold
  • Positive bronchoalveolar lavage (BAL) culture or PCR 2
  • Serum galactomannan index >0.5 or serum LFA index >0.5
  • BAL galactomannan index ≥1.0 or BAL LFA index ≥1.0
Sino-nasal diseases
  • Mold recovered by culture of sinus aspirate samples
  • Microscopic detection of fungal elements in sinus aspirate samples indicating a mold
Aspergillosis only
  • Galactomannan antigen detected in plasma, serum, BAL, or CSF
    • Any 1 of the following:
      • Single serum or plasma: ≥1.0 (0.5 for ICU or COVID patients) [@Bassett2021EORTCMSGERC] [@Koehler2021Definingmanaging]
      • BAL fluid: ≥1.0 (0.8 for ICU patients)
      • Single serum or plasma: ≥0.7 and BAL fluid ≥0.8
      • CSF: ≥1.0
  • Aspergillus PCR
    • Any 1 of the following:
      • Plasma, serum, or whole blood 2 or more consecutive PCR tests positive 2
      • BAL fluid 2 or more duplicate PCR tests positive (or single with Ct < 36) 2
      • At least 1 PCR test positive in plasma, serum, or whole blood and 1 PCR test positive in BAL fluid
  • Aspergillus species recovered by culture from sputum, BAL, bronchial brush, or aspirate (+ cytology or direct microscopy for ICU patients)
Pulmonary CAPA: At least one of the following
  • Microscopic detection of fungal elements in bronchoalveolar lavage, indicating a mold
  • Positive bronchoalveolar lavage (BAL) culture 2
  • Serum galactomannan index >0.5 or serum LFA index >0.5
  • BAL galactomannan index ≥1.0 or BAL LFA index ≥1.0
  • ≥2 positive aspergillus PCR tests in plasma, serum, or whole blood 2
  • 1 positive aspergillus PCR in BAL (Ct <36) 2
  • 1 positive aspergillus PCR in plasma, serum, or whole blood + 1 positive in BAL (any threshold cycle) 2

Possible

Immunocompromised patients

  • Host factors + clinical features

CAPA

Clinical
  • Pulmonary infiltrate (chest CT) or cavitating infiltrate (not attributed to another cause)
Mycological: At least one of the following
  • Microscopic detection of fungal elements in non-bronchoscopic lavage indicating a mold
  • Positive non-bronchoscopic lavage culture 2
  • Single non-bronchoscopic lavage GM index >4.5
  • ≥2 Non-bronchoscopic lavage GM index >1.2
  • Non-bronchoscopic lavage GM index >1.2 + another non-bronchoscopic lavage mycology test positive (non-bronchoscopic lavage PCR or LFA)

References

  • Bassetti, M., Azoulay, E., Kullberg, B.-J., Ruhnke, M., Shoham, S., Vazquez, J., Giacobbe, D.R. & Calandra, T. (2021) EORTC/MSGERC Definitions of Invasive Fungal Diseases: Summary of Activities of the Intensive Care Unit Working Group. Clinical Infectious Diseases. 72, S121–S127. doi:10.1093/cid/ciaa1751.
  • Donnelly, J.P., Chen, S.C., Kauffman, C.A., Steinbach, W.J., Baddley, J.W., et al. (2020) Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clinical Infectious Diseases. 71 (6), 1367–1376. doi:10.1093/cid/ciz1008.
  • Koehler, P., Bassetti, M., Chakrabarti, A., Chen, S.C.A., Colombo, A.L., et al. (2021) Defining and managing COVID-19-associated pulmonary aspergillosis: The 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. The Lancet Infectious Diseases. 21 (6), e149–e162. doi:10.1016/S1473-3099(20)30847-1.

  1. Hematologic malignancy refers to active malignancy, in receipt of treatment for this malignancy, and those in remission in the recent past. These patients would comprise largely acute leukemias and lymphomas, as well as multiple myeloma, whereas patients with aplastic anemia represent a more heterogeneous group of individuals and are not included. ↩↩↩

  2. In case of patients with chronic obstructive pulmonary disease or chronic respiratory disease, the PCR or culture results should be confirmed by galactomannan testing to rule out colonisation or chronic aspergillosis. ↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩↩

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內專考古題感染科試題

  1. 食媒性疾病，以下哪些配對最不正確？
    A. Listeriosis與乳酪
    B. Campylobacter jejuni與未煮熟雞肉
    C. Salmonella與生雞蛋
    D. Norovirus與生蠔或污染的水
    E. Q fever與生牛肉
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Fever

source: Harrison's Principles of Internal Medicine, 21e

正常體溫

  • 體溫由下視丘控制
  • 根據一項對35,000多名年齡≥18歲的個體進行的例行醫療訪問研究，平均口腔溫度為36.6°C（95%置信區間為35.7-37.3°C）。根據這項研究，健康個體99%百分位數的體溫定義為發燒，即超過37.7°C（99.9°F）
  • 體溫具有晝夜和季節變化，早上8點和夏季時最低，而下午4點和冬季時最高
  • 肛溫通常比口腔溫度高0.4°C（0.7°F）
  • 在育齡女性中，排卵前兩週的早晨體溫通常較低；排卵時體溫上升約0.6°C（1°F），並保持至月經來
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Infections in Immunocompromised Hosts

source: Pocket Medicine, 2022

  • Many Pts have ≥1 risk (eg, DM, ESRD, transplant, extremes of age)
  • Accurate dx of opportunistic infections and targeted Rx key in this population
  • The following is not an exhaustive list, but a delineation of common or classic etiologies

Tuberculosis

source: Pocket Medicine, 2022, 台灣肺結核診治指引第七版

Definitions

  • Primary: new Mycobacterium tuberculosis (TB) in a naïve host; symptomatic or asymptomatic; 90% of infected normal hosts will never develop clinically evident disease
  • Latent: well-controlled infection without clinical or radiographic evidence of active disease; can persist for years to decades
  • Reactivated: activation of latent; more likely in the setting of immunosuppression.
  • Milliary: disseminated lympho-hematogenous spread due to primary or reactivated TB
  • Multidrug-resistant (MDR): resistant to isoniazid (INH) & rifampin. Can occur as 1° infxn.
  • Extensively drug-resistant (XDR): resistant to INH, rifampin (RIF), fluoroquinolones (FQ), and at least one of amikacin, kanamycin, or capreomycin

CORONAVIRUS DISEASE 2019 (COVID-19) / SARS-COV-2 INFECTION

Source: Pocket Medicine, 2022; 台灣診治指引第二十八版

up:: 專師考試解題

微生物學與流行病學

  • 透過呼吸道顆粒在人與人之間傳播；無症狀與症狀前的傳播可能發生
  • 潛伏期：最長可達14天，從暴露到症狀出現的中位時間為4-5天
  • 確診病人發病==前2天==即可能具傳染力
  • 確診病人上呼吸道檢體可持續檢測SARS-CoV-2核酸陽性平均達==兩週==以上，且下呼吸道檢體檢出病毒的時間可能更久
  • 輕症個案在發病==10日後==即無法從上呼吸道檢體成功培養出病毒（部分重症個案或免疫不全者可能延長至20日），此時這些個案的病毒量均很低（ Realtime PCR Ct 值高），目前也沒有證據顯示此時這些個案能傳播疾病

HIV/AIDS

source: Pocket Medicine, 2022

Definition & Clinical Manifestations

  • Acute HIV: rash, lymphadenopathy, fever, oral ulcers, pharyngitis, myalgias, diarrhea
    • Presents ˜2-6 wk after exposure; not all HIV infections result in symptoms of acute HIV
  • AIDS: HIV + CD4 <200/mm3 or AIDS-defining opportunistic infection (OI) or malignancy

HIV/AIDS

source: Pocket Medicine, 2022

Definition & Clinical Manifestations

  • Acute HIV: rash, lymphadenopathy, fever, oral ulcers, pharyngitis, myalgias, diarrhea
    • Presents ˜2-6 wk after exposure; not all HIV infections result in symptoms of acute HIV
  • AIDS: HIV + CD4 <200/mm3 or AIDS-defining opportunistic infection (OI) or malignancy

Skin and soft tissue infections

Definitions

  • Cellulitis: infection of dermis and subcutaneous tissue characterized by erythema, warmth, tenderness, and swelling; often occurs as a result of skin breaches (JAMA 2016;315:3)
  • Skin abscess: subcutaneous collection of pus
  • Staph toxic shock syndrome: rapid onset fever, rash, hypotension, and multiorgan injury. Staph aureus culture are not necessary for diagnosis. Often associated with packing (tampon, nasal packing). Management may require surgical debridement + antibiotics

敗血症與休克

source: Pocket Medicine, 2022

休克

  • 組織缺氧，因為組織灌流降低，進而降低組織氧氣供應和/或增加氧氣消耗或氧氣利用不當
  • 典型的體徵包括低血壓（收縮壓 <90 mmHg 或收縮壓下降 >40 mmHg）、心搏過速、少尿（尿量 <0.5 cc/kg/h）、意識變化、代謝性酸中毒 ± 乳酸增加
  • 診斷困難，因為全身性血管阻力（SVR）增加可能維持收縮壓，但組織灌流差；休克指數（心率/收縮壓）>0.9 和脈壓[(收縮壓 - 舒張壓)/收縮壓] <25% 是顯著休克的線索

Latent tuberculosis infection

source: Pocket Medicine, 2022; 台灣肺結核診治指引

Whom to screen

  • 一個月內新生兒：都要治療
  • Open TB：都要檢查
  • Smear (-), culture (+)：<13歲、免疫力低下接觸者和同住家人要檢查
  • Culture(-)：照CXR即可
  • 肺外結核、指標個案<5歲：≥5歲接觸者照CXR
  • 1個月至未滿2歲：TST x 2 (一個月內、暴露滿八週後且與前次間隔八週）
    • 判讀標準：已打BCG ≥ 10mm，未打BCG, HIV, 接受anti-lymphokines 或其他免疫抑制治療者 ≥ 5mm為陽性
    • 治療期滿後TST < 5mm再補打BCG
  • 2歲以上：暴露滿八週後IGRA

HIV長效針劑

CDC申請條件

  • 18歲以上成人。
  • 近6個月內HIV病毒量<50 copies/mL。
  • 每日口服藥物有困難者，並請敘明理由，如：
    • 吞嚥藥物有困難。
    • 有生理或心理等疾病，不適合每日服藥。
    • 口服藥物產生副作用（如：暈眩、嘔吐等）。
    • 其他
  • 同意配合進行2個月一次的注射。
  • 未感染B型肝炎病毒。
  • 過去無病毒抑制失敗、未對CAB或RPV具有已知或疑似抗藥性。
  • 未使用會與CAB或RPV有明顯藥物交互作用之藥物。
  • 女性未懷孕或未有備孕計畫。
  • 潛伏結核感染（LTBI）檢驗為陰性，或已完成TB/LTBI治療。

DAA

Glecaprevir/pibrentasvir (Maviret)

  • 3# QD WM，Child-Pugh B/C不可使用，腎功能不佳可使用
  • 限使用於 HCV RNA 為陽性及無肝功能代償不全之病毒基因型第 1 型、第 2 型、第 3 型、第 4 型、第 5 型或第 6 型 12 歲（含）以上病患
  • 給付療程如下，醫師每次開藥以 4 週為限
    1. 未曾接受治療之患者，給付 8 週
    2. 曾接受含 (peg)interferon 及 ribavirin 及合併或不合併 sofosbuvir 治療組合之患者
      1. 基因型第 1 、 2 、 4 、 5 或 6 型：
        1. 無肝硬化者，給付 8 週
        2. 具代償性肝硬化 (Child Pugh score A) 者，給付 12 週
      2. 基因型第 3 型，且無肝硬化或具代償性肝硬化 (Child Pugh score A) 者，給付16 週
    3. 曾接受含 NS5A 抑制劑或 NS3/4A 蛋白酶抑制劑治療之基因型第 1 型患者：
      1. 若曾接受 NS3/4A 蛋白酶抑制劑治療，但未曾接受 NS5A 抑制劑治療者，給付12 週
      2. 若曾接受 NS5A 抑制劑治療，但未曾接受 NS3/4A 蛋白酶抑制劑治療者，給付16 週