Interactive session: adapting to antibiogram Thong Phe Heng Vengchhun Felix Leclerc Erika Vlieghe
Case 1 63 y old woman Dx: urosepsis? After 2 d: intermediate result: Gram-negative bacilli Empiric antibiotic treatment: ceftriaxone +/- amikacin RISK FACTORS FOR ESBL+ E coli Older age History of UTI Presence of urinary catheter History of recent urological surgery Recent intake of antibiotics
Another 2 d later Blood culture: Escherichia coli Urine culture: Escherichia coli Antibiogram: Amoxicillin R Amoxicillin/clavulanic acid S Amikacin S Ceftriaxone S Ceftazidime S Cotrimoxazole R Ciprofloxacin S Gentamicin R Meropenem S
Which treatment will you give now? PO amoxycillin IV amoxycillin PO amoxycillin-clavulanic acid IV ciprofloxacin PO ciprofloxacin IV ceftriaxone IV ceftriaxone + amikacin IV meropenem
Another 2 d later Antibiogram: Amoxicillin R Amoxicillin/clavulanic acid S Amikacin S Ceftriaxone S Ceftazidime S Cotrimoxazole R Ciprofloxacin S Gentamicin R Meropenem S IV ceftriaxone 2 g qd or IV ciprofloxacin 500 mg q12 If no more fever 48 h: PO ciprofloxacin 500 mg q12 Total duration 7-10 days
But imagine another patient Another antibiogram: Amoxicillin R Amoxicillin/clavulanic acid S Amikacin S Ceftriaxone R Ceftazidime R Cotrimoxazole R Ciprofloxacin R Gentamicin R Meropenem S
Which treatment will you give now? PO amoxycillin IV amoxycillin PO amoxycillin-clavulanic acid IV ciprofloxacin PO ciprofloxacin IV ceftriaxone IV ceftriaxone + amikacin IV meropenem
Amoxicillin R Amoxicillin/clavulanic acid S Amikacin S Ceftriaxone R Ceftazidime R Cotrimoxazole R Ciprofloxacin R Gentamicin R Meropenem S Ceftriaxone R suggest presence of ESBL = resistance for all beta-lactam drugs (exc. Carbapenem, cefepime) =often co-resistance to ciprofloxacin, gentamicin, cotrimoxazole Here you need to use Meropenem 1 g q8 x 10 d
Case 3 15 year old female student 10 d high fever, abdominal pain BP 82/43 mmhg RR 24/, O2 Sat 97%, temp 39.3 C Hb 11.9 g/dl WBC 7200/µl sgot/sgpt 91/28 Malaria smear negative CXR negative
2 days later Persisting high fever and abdominal pain Blood cultures show Gram negative bacilli
Another 2 days later Blood cultures Salmonella Typhi Antibiogram Ampicillin R Amoxycillin-clavulanic acid I Cotrimoxazole R Chloramphenicol R Ciprofloxacin R Ceftriaxone S
Which treatment do you give? PO amoxycillin PO Augmentin PO ciprofloxacin IV ceftriaxone IV imipenem IV vancomycin
Which treatment do you give? PO amoxycillin PO Augmentin PO ciprofloxacin IV ceftriaxone IV imipenem IV vancomycin
But imagine another typhoid patient: Blood cultures Salmonella Typhi Antibiogram Ampicillin R Amoxycillin-clavulanic acid I Cotrimoxazole R Chloramphenicol R Nalidixic acid S Ciprofloxacin S Ceftriaxone S
Which treatment do you give? PO amoxycillin PO Augmentin PO ciprofloxacin IV ceftriaxone IV imipenem IV vancomycin
Which treatment do you give? PO amoxycillin PO Augmentin PO ciprofloxacin IV ceftriaxone IV imipenem IV vancomycin
Salmonella Typhi If possible, treat with ciprofloxacin If nalidixic acid R cipro R Then: IV ceftriaxone 2 g qd x 10 d Or PO azithromycin 1000 mg d1, then 500 mg/d x 7 d
Case 4 40 y/o man Prey Veng History DMII (3years) Malaria in 1980 Liver abscess (4 & 2 months ago) Medication: herbal medicine Amoxicillin Diamicron. No known allergy His wife and 3 children are healthy
Evolution amoxycillin (2 w) no improvement Ceftriaxone + metronidazole (5d) no improvement Blood cultures: Burkholderia pseudomallei
How to treat? Continue IV ceftriaxone + metronidazole Switch to IV Augmentin Switch to IV ceftazidime Switch to IV cotrimoxazole Switch to IV chloramphenicol + amikacin other
How to treat? Continue IV ceftriaxone + metronidazole Switch to IV Augmentin Switch to IV ceftazidime Switch to IV cotrimoxazole Switch to IV chloramphenicol + amikacin other
Melioidosis: intensive phase IV ceftazidime 50mg/kg up to 2g q6 x minimum 10 days IF NO CEFTAZIDIME: IV Augmentin 20/5 mg/kg q4 at least 10 days OR IV/PO cotrimoxazole (IV or PO 8/40mg/kg q12 up to 320/1600mg q12) +/- doxycycline 2.5 mg/kg up to 100mg q12 (dose) OR IV ceftriaxone (at larger doses than usual 50mg/kg up to 2g qd) at least 10 days + cotrimoxazole (IV or PO 8/40mg/kg q12 up to 320/1600mg q12)
Melioidosis: continuation phase Cotrimoxazole 8/40mg/kg up to 320/1600mg q12 x at least 3 months (= 12 weeks) OR For children and pregnant women: Augmentin 20/5mg/kg up to 1500/375mg q8 x at least 3 months (=12 weeks) may need treatment for 6 months
Evolution Clinical improvement, no more fever on 08/06/10. 14.06.10: switch to Cotrimoxazole with Doxycyclin and discharge home Ambulatory follow up for Melioidosis treatment and diabetes: he was ok at followup on 26/07/10.
Interpretation of antibiograms
Step by step 1. Look for the name of the bacteria 2. Look for the first choice antibiotic 3. If S prescribe this 4. If R second choice antibiotic 5. If possible, de-escalate
1. Look for the name of the bacteria Is this a true pathogen (causing the disease) e.g. Staphylococcus aureus Choose antibiotics! E coli and other Gram negative bacilli Or is this more likely a contaminant e.g. Coagulase negative Staphylococci Bacillus Corynebacterium No antibiotics needed!!
2. Look for the first choice antibiotic Each bacterium has first choice antibiotics Best activity, smallest spectrum, Should be written in treatment guideline Staphylococcus aureus cloxacillin Pneumococ penicillin G Salmonella species ciprofloxacin E. coli ciprofloxacin, ampicillin, Augmentin
3. If the first choice AB shows S Then you prescribe the first choice AB! According to your local guidelines & availability With the smallest spectrum possible Dose according to the disease severity e.g. S aureus causing skin infection» Cloxacillin PO 500 mg q6 S aureus causing blood stream infection/sepsis» Cloxacillin IV 1-2 g q4-6
4. If the first choice shows R Use the second choice antibiotic As listed in guidelines Or: with known good activity against this bacterium AND with the smallest spectrum possible
Example1: Staphylococcus aureus Cloxacillin R (MRSA) Serious infection use vancomycin if possible Mild infection use cotrimoxazole (or lincomycin) if S
Example 2: E. coli Ampicillin R use Augmentin or ciprofloxacin Ciprofloxacin R use Augmentin (if S) or Ceftriaxone Augmentin R check if also Ceftriaxone R (likely ESBL+) use ciprofloxacin, cotrimoxazole (if S) if all other AB R: use meropenem (if available) Ceftriaxone R serious infections: use meropenem (if available) mild infections: use cotrimoxazole, ciprofloxacin (if S) UTI: use nitrofurantoin (if S) Use only meropenem if serious and if you have no other possibility
Beta-lactamases
ESBL Extended spectrum beta-lactamase Treatment options: Severe disease: carbapenem( meropenem or imipenem) amikacin (use ALWAYS in combination) Moderate disease: Is treatment necessary, is I&D alone enough, Check if you can use cotrimoxazole or ciprofloxacin Only if no other option use carbapenem UTI: nitrofurantoin (if S )
4. If possible, de-escalate: Treatment simplification/narrowing of microbiological spectrum Narrowing the spectrum Kill the bacteria as selectively as possible Use the least toxic, easiest and most affordable drug BROAD SPECTRUM ANTIBIOTIC NARROW SPECTRUM ANTIBIOTIC
Broad spectrum AB Ceftriaxone Amoxyclavulanate Piperacillin-tazobactam Meropenem Examples Narrow spectrum AB Cloxacillin (for Staphylococci) Ampicillin, penicillin (for Streptococci) Temocillin (for E. coli)
Examples of de-escalation Staphylococcus aureus, methicillin sensitive (MSSA) IV/PO flucloxacilline (Floxapen ) Streptococcus pneumoniae, penicillin susceptible S) IV Penicilline/amoxycilline Salmonella Typhi, ciprofloxacin sensitive ciprofloxacin, (azithromycin) E. coli: more difficult. Depends on antibiogram IV temocillin, PO ciprofloxacine, (IV/PO amoxyclavulanate)
Usual duration of treatment Bacteremia (blood stream infection): 10-14 days Typhoid fever: 7-10 days Community acquired pneumonia: 7 days UTI: 3-5 days 7 d if nitrofurantoin used Skin and soft tissue infection: 7 days Meningitis: 10-14 days 21 d if Streptococcus suis, S. aureus, Listeria, Pseudomonas) Osteomyelitis/septic arthritis: 4-6 weeks
Usual doses (1) Ampicillin For (suspected) endocarditis: 1-2 g q4-6 IV For mild/local infections: 1 g q8 PO Augmentin For respiratory tract: 1 g q8 PO For urinary/abdominal: 500 mg q6-8 PO For melioidosis: 1 g q4-6 IV Azithromycin For typhoid fever 500-1000 mg qd PO Cloxacillin For bacteremia/endocarditis: 1-2 g q4-6 IV For skin/soft tissue infection: 500 mg q6 PO
Usual doses (2) Ciprofloxacin: 500 mg q12 Cotrimoxazole For MRSA and Gram-negative infections: 5/25 mg/kg q12 For melioidosis: 8/40 mg/kg q12 Ceftriaxone For meningitis 2 g q12 For other indications 2 g qd Ceftazidime For melioidosis: 1 g q8 Meropenem: 1 g q8 (ONLY FOR SEVERE INFECTIONS) Nitrofurantoin: 100 mg q8 x 7 days (UTI ONLY)