05 Bloodstream infections

unideb2025

What is bacteraemia?

1. Microbiological diagnosis

2. Presence of bacteria in the blood

Does bacteremia necessarily mean illness?

No

Does bactere,ia necessarily mean a need for treatment (e.g.

CNS)?

No

possible reason for non-pathologic bacteremia result

contamination of blood culture (e.g., skin, bottle, procedure)

What is sepsis?

1. a life-threatening organ dysfunction resulting from dysregulated host responses to infection

2. clinical diagnosis, hemoculture not always positive

3. a serious disease – high mortality rate

Outcome of sepsis is determined by?

1. early identification

2. appropriate management

Tools that help identification of septic patients:

1. SIRS criteria

2. qSOFA

3. lactate

4. (PCT?)

none is a validated screening tool

Is sepsis a medical emergency?

Yes, treatment and resuscitation should start immediately

When should we take hemocultures in sepsis patients?

immediately

What is septic shock?

1. a subset of sepsis

2. underlying circulatory, cellular, and metabolic abnormalities are profound enough to substantially increase the risk of mortality

3. despite adequate fluid resuscitation, patients have hypotension requiring vasopressors to maintain a mean arterial blood pressure above 65 mmHg and have an elevated serum lactate concentration of more than 2 mmol/L³

typical signs of sepsis

1. Fever or hypothermia

2. Tachycardia

3. Tachypnoe (30 breathes/min)

4. Changes in mental state.

What other signs can be seen in sepsis?

1. Hypotension (absence doesn't rule out sepsis)

2. ventilatory failure (even in the absence of infectionin the lungs)

3. Oliguria

4. Skin is usually mottled

5. CRT increased

Can organ dysfunction develop even with normotension?

yes

What can sepsis lead to?

1. organ failure

2. acidosis

3. death

typical lab signs of sepsis

1. Elevated lactate

2. WBC ↑↓

3. Elevated CRP and PCT

4. Worsening kidney function

5. Elevatedliver liver enzymes and bilirubin

6. Coagulation disorders

treatment of sepsis

1. Immediate fluid resuscitation:

2. Considering infection as a cause continuously (searching for alternative diagnosis)

3. Source control as soon as possible.

Immediate fluid resuscitationin sepsis

1. 30ml/kg crystaloid bolus within the first 3 hours

2. Goal: MAP 65 mmHg &decreasing lactate

When should we administer AB in sepsis treatment?

1. In case of shock: administration of AB within 1 hour

2. In the absence ofshock: within 3 hours

Don't wait for PCT

choice of antibiotics in sepsis treatment

Anti-Gram-negative:

1. High risk of MDR infection: 2 agents

2. Low risk of MDR infection: 1 agent

Anti-Gram-positive:

1. High risk risk of MRSA infection: needs coverage

2. Low risk of MRSA infection:nocoverage

Anti-fungal: if there is a high risk of fungal infection, cover it

administration of AB in sepsis treatment

According to Pk/PD+TDM (therapeutic drug monitoring)

1. Beta-lactams (T>MIC): loading bolus + prolonged infusion (at least half of the dosing interval time) → lower mortality

2. Vancomycin (AUC/MIC): 1 g loading dose, then according to kidneyfunction

3. Colistin (AUC/MIC): 9 MU loading dose, then according to kidneyfunction

4. FQ (AUC/MIC,Cmax/MIC): cipro 3x400mg- mg—kidney function!

5. AG (Cmax/MIC): once daily - body weight, kidney function

6. Azoles (AUC/MIC): (Flu: firstday: loadingdose)

How soon should we eliminate the source of infection in sepsis?

is soon as possible (whithin 6-12 h) → lower mortality

How do we eliminate the source of infection in sepsis?

1. Drainage (abscess)

2. Debridement (necrotictissue)

3. Removal of potentially infected device (CVC,PVC,ARC, prosthesis, etc.)

4. Removal of infected organ (appendectomy, cholecystectomy, limbamputation, heart valve etc.)

Can patients stabilize or improve with only rapid resuscitation and appropriate antibiotics?

No, there is a need for adequate source control.

de-escalation in sepsis

1. Consider daily if possible

2. Replace empirical broad-spectrum antimicrobial treatment by using a narrower antimicrobial therapy according to culture results

3. Stop all antimicrobials, if a non-infectious cause is diagnosed

4. Shorter-duration therapies

5. PCT can be helpful in stopping antibiotics

How will PCT change in sepsis patients if AB is appropriate?

PCT halves everyday

What are exceptions for shorter duration therapies in de-escalation in sepsis?

1. endocarditis

2. osteomyelitis—spondylodiscitis

3. brain abscess

4. non-drainable

5. encapsulated infections—e.g. small abscesses,prostatitis, S. aureus bacteremia, candidaemia etc.

S. aureus

Gram-positive facultative anaerobic coccus

Pyogenic pathogen

Resistant strains of S, aureus

1. MSSA

2. MRSA

3. hVISA

4. VRSA

What can S. areus cause?

1. skin & soft tissue infection

2. bone & joint infection

3. abscesses anywhere (brain, abdomen, retroperitoneum, etc.)

4. endocarditis

mortality rate of S. aureus bacteraemia

20-40%

treatment failure of S. aureus bacteraemia

1. death within 30 days following treatment

2. persistent bacteremia >10 days after initiation of appropriate therapy

3. recurrence of bacteremia within 60 days of discontinuing therapy

4. particularly in the setting of infection due to MRSA

potential portals of entry of S. aureus bacteraemia

1. skin & soft tissue infection—careful anamnesis and

   physical examination (diabetic foot, slow-healing

   wound, folliculitis, etc.)

2. presence of indwelling prosthetic devices (including

   intravascular catheters, orthopedic hardware, and

   cardiac devices).

How do we deal with S. aureus bacteraemia?

1. all cases must be treated

2. even one hemoculture

complications of S. aureus bacteraemia

Seek for metastatic infection (can occur in up to 30% of cases)

1. bone or joint pain (particularly back pain, suggesting vertebral osteomyelitis, discitis, and/or epidural abscess)

2. protracted fever and/or sweats (suggestive of endocarditis)

3. abdominal pain (particularly left upper quadrant pain, which may reflect splenic infarction)

4. costovertebral angle tenderness (which may reflect renal infarction or psoas abscess)

5. headache (which may reflect septic emboli/brain abscess)

physical examination of S. aureus bacteraemia

1. careful cardiac examination for signs of new regurgitant murmurs or heart failure

2. clinical stigmata of endocarditis, including evidence of small and large emboli with special attention to the fundi, conjunctivae, skin, and digits

3. neurological evaluation

4. Pain (back, abdominal, head, Osler’s nodes, etc.)

What are advantages of bedside infectious disease consultation in S. aureus bacteraemia?

1. lower 90-day mortality rate

2. fewer deaths

3. fewer relapses

4. lower readmission rates

What does one positive hemoculture indicate?

a clinically significant finding that should prompt clinical evaluation and initiation of empiric therapy

When is obligatory echocardiograohy most sensitive?

when performed five to seven days after the onset of bacteremia

examples of imaging techniques tailored to findings on history and physical examination in bacteremia

1. back pain: vertebral MRI

2. Abdominal symptoms: abdominal CT

3. headache: brain MRI

How do we document clearance of bacteremia?

repeated follow-up blood cultures

risk factors of infective endocarditis that indicates the importance of TEE

1. Persistent S. aureus bacteremia despite appropriate antimicrobial therapy

2. Unknown duration of bacteremia (i.e., community-acquired infection)

3. Presence of cardiac prosthetic material

4. Presence of predisposing valvular abnormality

5. Absence of evident removable source of bacteremia

6. Hemodialysis dependency

7. Evidence of infection involving the back (osteomyelitis, discitis, and/or epidural abscess)

8. Presence of peripheral stigmata for IE

9. Intravenous drug use

empiric treatment of S, aureus bacteremia

1. vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose);

2. daptomycin (6 mg/kg intravenously once daily)

antibiotic treatment targeted for MSSA

1. nafcillin (2 g IV every four hours), oxacillin (2 g IV every four hours), or flucloxacillin (2 g IV every six hours)

2. cefazolin (2 g IV every eight hours)

What treatment, along with definitive treatment, has a significantly better outcome in S. aureus bacteremia?

a beta-lactam from day 4 to 14 of treatment

treatment duration for uncomplicated S. aureus bacteremia

14 days of intravenous therapy from the first negative blood culture

treatment duration for complicated S. aureus bacteremia

1. 4-12 weeks

2. depending on the site of metastatic infection—e.g.endocarditis, osteomyelitis, septic arthritis, prosthetic joint infection, etc.

uncomplicated bacteremia

1. Infective endocarditis has been excluded via echocardiography.

2. No indwelling devices (such as prosthetic heart valves or vascular grafts) are present.

3. Follow-up blood cultures negative drawn two to four days after initiating intravenous antistaphylococcal therapy and removing the presumed focus of infection (if present) is done

4. The patient defervesced within 48 to 72 hours after initiating intravenous antistaphylococcal therapy and removal of the presumed focus of infection (such as debridement of soft tissue infection or intravascular catheter removal).

5. There is no evidence of metastatic staphylococcal infection on physical examination.

How much mortality rate does candidemia increase?

in the range of 20–49%

What has a major impact on hospital mortality?

Timing of antifungal therapy

diagnostic blood culture in candidemia

1. 3 pairs daily

2. sensitivity: 50-75%

3. one single HC positive for any Candida species should prompt treatment—2-5 days to give result

Mannan-antimannan test in candidemia

1. sensitivity: 80%

2. specificity: 85%

3. NPV > 85%

4. very useful for ruling out infection

5. Serial testing needed (twice a week)

6. Positive 6 days on average prior blood cultures

β-1,3-D-glucan detection (BDG)

1. panfungal marker (not specific for Candida)

2. NPV > 85%

3. very useful for ruling out infection

4. Serial determinations (twice a week) are recommended.

treatment timing of candidemia

1. Prophylaxis: giving antifungal therapy to patients who don’t yet have invasive fungal infection to avoid it.

2. Empiric treatment (fever-driven)

3. Pre-emptive (diagnosis-driven)

4. Targeted: based on a positive hemoculture

prophylaxis treatment of candidemia

1. Fluconazole

2. against invasive candidiasis

3. recommended in patients who recently underwent abdominal surgery and had recurrent gastrointestinal perforations or anastomotic leakage

Empiric treatment (fever-driven) of candidemia

Treating of a patient at risk for invasive candidiasis who is persistently febrile with no microbiological

evidence of infection.

Pre-emptive treatment (diagnosis-driven) of candidemia

1. Microbiological evidence of candidiasis without proof of invasive fungal infection.

2. β-D-glucan detection in serum or plasma prompting antifungal treatment is marginally supported.

Targeted treatment of candidemia

• Indication: Candida isolated from a single peripheral blood culture or a single central-line blood culture defines candidaemia and should promt treatment.

• Drug of choice:

1. Echinocandin (anidula-, caspo- or micafungin) (AI)

2. Amphotericin B liposomal 3 mg/kg (BI)

3. Voriconazole 6/3 mg/kg/day (BI)

duration of treatment of candidemia

1. For uncomplicated candidaemia, treatment duration of 14 days after the end of candidaemia is recommended.

2. Switching to oral treatment can be considered after 10 days of intravenous therapy is the patient is stable and the strain is susceptible.

other possible measures for candidemia

1. Removal of indwelling intravascular catheters (When catheter removal is not possible, lipid-based amphotericin B formulation or an echinocandin is preferable.

2. TEE

3. Fundoscopy (chorioretinitis or endophthalmitis)→Emp. Th.: liposomal amphotericin B either alone or combined with flucytosine; Targ.Th.: in susceptible isolates fluconazole or voriconazole.

candida-positive cultures: respiratory interpretation

No treatment indicated (to be considered only as colonisation)

candida-positive cultures: urinary interpretation

1. Asymptomatic candiduria: should not be treated (but: removal of catheter is useful)

2. Symptomatic cystitis: fluconazole

3. Pyelonephritis: fluconazole or a lipid-based amphotericin

4. Treat only when signes and symptomes + pyuria are present, not simple candiduria!

candida-positive cultures: ocular interpretation

• Usually causes pain and disturbed vision

• Chorioretinitis or endophthalmitis

• Treatment:

1. Liposomal amphotericin B either alone or combined with flucytosine

2. In susceptible isolates, fluconazole or voriconazole are the drugs of choice

3. In the case of vitreal involvement, vitrectomy and intravitreal injection of amphotericin B

candida-positive cultures: meningitis

1. Very rare—few data only, no strong recommendation

2. Treatment: liposomal amphotericin B combined with flucytosine or with fluconazole if isolate is susceptible

3. Treat for 2-10 weeks

candida-positive cultures: endocarditis

Native valve:

• Patients should undergo surgery within the first week

• liposomal amphotericin B or caspofungin, either one has been combined with flucytosine

Prosthetic valve:

• valve replacement surgery needs be performed as soon as possible

Other intracardial devices:

• Removal is mandatory

Bone and joint candidiasis treatment

1. liposomal or lipid complex amphotericin B to be followed by fluconazole, or—if isolate is susceptible—fluconazole monotherapy may be used from the beginning

2. Removal of prosthesis

3. If joint prosthesis cannot be removed, lifelong fluconazole suppressive therapy is indicated

epidemiology of infective endocarditis

1. older patients

2. result of health care-associated procedures, either in patients with no previously known valve disease or in patients with prosthetic valves

3. male:female ratio is 2:1

Streptococci pathogen of endocarditis

1. Oral: S. sanguis, S. mitis, S. salivarius, S. mutans, Gemella morbillorum almost always susceptible to Penicillin G.

2. S. sanginosus, S. intermedius, S. constellatus: tend to form abscesses and cause haematogenously disseminated infection

3. Group D streptococci form the ‘Streptococcus bovis/Streptococcus equinus’ complex, including commensal species of the human intestinal tract. They are usually sensitive to penicillin G, like oral streptococci

Enterococci pathogen of endocarditis

• E. faecalis, E. faecium, (E. durans)

• AB sensitivity:

1. Ampicillin/amoxicillin ± beta-lactamase inhibitor

2. Vancomycin / teicoplanin

3. Gentamycin

4. Tigecyclin

5. Linezolid / tedizolid

Staphylococci pathogen of endocarditis

1. S. aureus

2. CNS – S. lugdunensis

reasons for culture-negative endocarditis

prior AB treatment

• causative organisms are most often oral streptococci or CNS

Fastidious organisms:

• nutritionally variant streptococci,

• fastidious Gram-negative bacilli of the HACEK group (Haemophilus arainfluenzae,H. aphrophilus, H. paraphrophilus, H. influenzae, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae, and K. denitrificans),

• Brucella

• fungi

Intracellular bacteria: 5 % of all IE. Diagnosis in such cases relies on serological testing, cell culture

or gene amplification.

• Coxiella burnetii (Q-fever)

• Bartonella

• Chlamydia

• Tropheryma whipplei

endothelium-related pathomechanism in endocarditis

• mechanical disruption of the endothelium

• non-bacterial thrombotic endocarditis (NBTE) facilitates bacterial adherence and infection

• Endothelial damage may result from:

1. mechanical lesions provoked by turbulent blood flow

2. electrodes or catheters

3. inflammation (rheumatic carditis)

4. degenerative changes in elderly individuals.

bacteremia-related pathomechanism in endocarditis

1. magnitude of bacteraemia

2. ability of the pathogen to attach to damaged valves

3. after invasive procedures

4. chewing and tooth brushing

bacteria-related pathomechanism in endocarditis

Classical IE pathogens (S. aureus, Streptococcus spp., and Enterococcus spp.) share the ability to

• adhere to damaged valves

• trigger local procoagulant activity

• nurture infected vegetations

Following colonization, adherent bacteria must escape host defences:

• escaping PMP-induced killing

What are PMPs?

1. platelet microbicidal proteins

2. produced by activated platelets

3. kill microbes by disturbing their plasma membrane

What is the most important thing in endocarditis diagnosis?

Suspition