Blood culture

• Anticipate to control blood cultures, to exclude a possible contamination in case of coagulase negative staphylococcus in culture
• Explore for possibly underlying endocarditis: risks factors, intravascular device, heart murmur, purpura, arthritis
• Check any cutaneous or nosocomial origin of infection: catheter, prosthesis, surgical scar, intravascular device
• Plan to monitor blood cultures, ideally after 48 hours of antibiotics, to ensure that they become negative

Start an intravenous anti-staphylococcal antibiotherapy

• (Cl)oxacillin 150mg/kg/day divided into 4 doses (maximum 12g/day)

If allergy to penicillin:

• Cefazolin 100mg/kg/d in 3 doses

Children

• Cefazolin 100-150 mg/kg/day in 3-4 doses

If argument for MRSA or nosocomial

• Vancomycin (alone or with Cefazoline if severity)

Adults

• Vancomycin 15 mg/kg/j en 1 h, bid (max. 4 g/j)

Children

• Vancomycin 30 mg/kg/day i.v. in 2-3 equally divided doses

If septic-shock or intravascular device infection

• Vancomycin 40 mg/kg/day IV continuous infusion after a loading dose of 30 mg/kg IV bolus over 2 hours (max: 4g/d) in a dedicated central venous catheter (venotoxicity)
• Monitor serum concentration at H48 and adjust to renal function
• Target residual levels between 15-20 mg/L 

Or

• If available: Daptomycin 10mg/kg/d (30-minutes infusion once a day)

• Explore for possibly underlying endocarditis for high-risk bacteria, like oral Streptococcus, Streptococcus gallolyticus or Enterococcus spp: risks factors, intravascular device, heart murmur, purpura, arthritis
• Check for origin of infection
• Plan to control blood cultures, ideally after 48 hours of antibiotics, to ensure that they become negative

First line of antibiotic treatment for this species is Amoxicillin

Adults

• Amoxicillin/Ampicillin 100-200 mg/kg depending on the situation (highest dose for endocarditis) i.v. in 4–6 doses, maximum 12g/d

Children

• First week of life (7 days or less): 50 mg/kg/dose 8 hourly
• 8 days of age & older: 50 mg/kg/ dose 6 hourly

Non-severe allergy

• 3GC as Ceftriaxone, 2g/d in one dose OR Cefotaxime 6g/d in 3 doses

Severe allergy

Adult

• Vancomycin 15 mg/kg/j in 1 hour, bid, max.4 g/j

Children

• Vancomycin 30 mg/kg/day i.v. in 2–3 equally divided doses OR Daptomycin 10mg/kg/d, 30-minutes infusion once a day

Community acquired

• 3GC as Ceftriaxone, 2g/d in one dose OR Cefotaxime 6g/d in 3 doses

Add

• Amikacin 30mg/kg/d in 1 dose if severity or in case of ESBL risk factors until antibiogram

View ESBL risk factors

If gram-negative diplococci

• 3GC as ceftriaxone 1g immediately
• check for meningitis, purpura fulminans, arthritis (Neisseria meningitidis) OR arthritis, sexually transmitted disease (N.gonorrhoeae)

View Actions in case of critical results

If nosocomial or if non-fermenting bacteria is suspected

• Piperacillin-tazobactam 16g/d in 4 doses OR 4GC as cefepime 6-8g/d in 3 doses OR 3GC as ceftazidime 6g/d in 3 doses

Add

Amikacin 30mg/kg/d in 1 dose if severity OR ESBL risk factors until antibiogram

View ESBL risk factors

If septic shock and ESBL risk factors

• Imipenem 1g/8h OR meropenem 2g/8h AND amikacin 30mg/kg/d in 1 dose

Reevaluate at 48h with antibiogram to decrease spectrum and stop amikacin

View Paediatric antibiotic dosage & route

This result raises the question of:

• Catheter infection: prescribe paired blood culture and urgent catheter removal in case of sepsis or septic shock
• Control negativation of blood culture under antifungal therapy, total duration treatment : 14 days after the first negative blood culture (if no endocarditis neither thrombophlebitis)
• Performing a venous Doppler ultrasound at the central line site to investigate septic thrombophlebitis 
• Endocarditis: perform a transthoracic echocardiography before the end of the treatment, ideally after 5-7 days after first positive blood culture

First-line treatment

• Fluconazole 12m/kg/d first day (maximal dose of 1200mg/d) and then 6mg/kg/d from day 2 oral or i.v.

If septic shock, and/or prior fluconazole treatment, in order of preference

• Caspofungine 70mg/d first day and 50mg/d from day 2, i.v. (keep Caspofungin dose of 70mg every day if weight >80kg)
• Liposomal Amphotericin B 3 mg/kg/d i.v. in 1 dose
• Amphotericin B Deoxycholate 1 mg/kg/day i.v. 2 hours infusion

• Metronidazole i.v. or oral 500mg/8h (consider adding ceftriaxone or cefotaxime in case or intra-abdominal infection)

If nosocomial:

• Piperacillin-Tazobactam 4g every 6-8 hours

If methicillin-sensible (MSSA):

• (cl)oxacillin 14 days

If methicillin-resistant (MRSA):

• Vancomycin OR Daptomycin (+/- consider adding aminoglycoside or Cefazolin in severe patient) 14 days

Switch to Per Os at day 7 if: 

• Negative blood culture
• Not immunocompromised
• No endocarditis at day 7 transthoracic echocardiography
• Optimal control of source infection
• No secondary foci

Available treatment for PO switch – oral biotherapy

• Clindamycin if Erythromycine sensitive
• Trimethoprim/Sulfamethoxazole
• Linezolide 
• Doxycycline
• Levofloxacine

Streptococcus spp, Enterococcus faecalis

• Amoxicillin 7 days

Enterococcus faecium

• Amoxicillin if sensitive, otherwise Vancomycin OR Linezolid for 7 days

Severe infections Imipenem or Meropenem then with antibiogram

• Piperacillin-tazobactam if MIC ≤ 8 mg/L

It is not recommended to use cefepime even if sensitive

Non-severe infections: avoid 3GC or 4GC for example Cefepime

Biliary infections after source control and antibiogram:

• Piperacillin-Tazobactam 16g/d if the MIC is ≤ 8 mg/L
• Levofloxacin and Metronidazole OR Ciprofloxacin AND Metronidazole
• Amoxicillin-Clavulanic acid

During 7 days

Urinary infections (including bacteremia) after source control and antibiogram:

• Piperacillin-Tazobactam 16g/d if the MIC is ≤ 8 mg/L
• Levofloxacin OR Ciprofloxacin
• Trimethoprim AND Sulfamethoxazole
• Temocillin
• Cefoxitin (if ESBL-producing E. coli)
• Aminoglycoside

Duration depending on infection site (7 to 14 days)

Other infections than biliary and urinary Imipenem or Meropenem then with antibiogram:

• Piperacillin-Tazobactam if MIC ≤ 8 mg/L for 7 days

It is not recommended to use Cefepime even if sensitive

View Actions in case of critical results

Severe infections

OXA 48 AND OXA 48 like:

• Ceftazidime-Avibactam (C/A)

KPC:

• Ceftazidime-Avibactam (C/A)
• Meropenem-Vaborbactam (M/V)
• Imipenem-Relebactam (I/R)

Metallo-BL type NDM: 

• Aztreonam + Ceftazidime-avibactam (Az/C/A)

• Cefiderocol (Cef) – specialist advice required

If carbapenemase identification is not available consider using Aztreonam + Ceftazidime-avibactam (Az/C/A)

For duration cf to infection type (no need for longer treatment duration even if carbapenemase)

Non-severe infections

Urinary tract infections

• Aminoglycoside (including Plazomicin when available)
• Potentially Tigecycline

Other infections

Use older antibiotics if feasible (specialist advice required)

Pseudomonas aeruginosa and Acinetobacter baumanii

• Ceftazidime
• Cefepime
• Piperacillin-tazobactam 16g/d

Consider combination therapy with Aminoglycoside (Amikacin) if severe at least until patient improvement

Multi-drug-resistant Pseudomonas aeruginosa

Expert advice is needed to discuss carbapenems or new beta-lactam association (like Ceftolozane-tazobactam)

Stenotrophomonas maltophilia

Non severe infection or sepsis

• Trimethoprim + sulfamethoxazole 8-12mg/kg/d of TMP content and Minocyclin 200mgx2/d

Septic shock or severe infection

• Aztreonam + Ceftazidime-avibactam (Az/C/A)

• Amoxicillin 200mg/kg/d in 4-6 doses if sensitive to Amoxicillin

If amoxicillin resistant: 

• Linezolid
• Daptomycin + Amoxicillin (even if Amoxicillin resistant)