ANTIBIOTIC GUIDELINES FOR THE EMPIRICAL TREATMENT OF SEPSIS IN IMMUNOCOMPETENT ADULTS Contents: Page 1-2
General guidance/ Current trends in Antibiotic Resistance
Page 3-6
Guidance on initial Antibiotic therapy by body site: Abdominal Infection Biliary Sepsis Bone and Joint Cellulitis IV Cannula Sepsis Endocarditis (sub acute) Urosepsis NB Meningitis and Pneumonia (see separate guidelines)
Page 7
Algorithm for the Empirical treatment of suspected severe infection, where MRSA is a possibility.
Page 8-10
Vancomycin and Gentamicin dosing / monitoring and calculation of GFR.
These guidelines detail the empirical antibiotic treatment of sepsis in immunocompetent adults. Please see separate guidelines for the treatment of neutropenic sepsis. In cases of sepsis in immunocompetent adults in whom the diagnosis is unknown, empirical therapy based upon the likeliest of sources of bacteraemia is necessary. If source of sepsis is unknown; please refer to the algorithm on page 8. Appropriate microbiological specimens should always be taken before starting antibiotics. This should include two sets (four bottles) of blood cultures taken from separate sites (20ml/set). Recent microbiology results (where available) should be reviewed to identify if the patient is at risk of sepsis with a more resistant organism, which may not respond to standard first line therapy.
Nottingham Antibiotic Guidelines Committee -1 -
Oct 2004
Review Oct 2006
Current trends in Antibiotic Resistance MRSA and Serious Infection At present in Nottingham up to 40% of Staphylococcus aureus bacteraemias /septicaemias in adult patients are due to MRSA, which will not be sensitive to the agents frequently used for S aureus sepsis ie flucloxacillin and cefuroxime. MRSA infection is more likely in current inpatients, but patients admitted from the community are at risk of MRSA infection if they have any of the risk factors listed below:
Recent treatment as an inpatient in the last 6/12 or outpatient with an indwelling line Previous MRSA infection / colonisation Long-term urinary catheter Resident of a nursing or residential home with breaks in their skin e.g. leg ulcers
Initial antibiotic treatment of sepsis of unknown aetiology or severe staphylococcal infections should therefore be altered to cover the possibility of MRSA in a patient who has any of these risk factors for MRSA infection (see algorithm page 7). Further therapy should be adjusted in light of the microbiological culture and sensitivity results. NB. Currently Gentamicin and Vancomycin are active against the MRSA strains circulating in Nottingham. Multiresistant Gram negative bacilli Recent local, national and international surveillance has identified a worrying increase in multiple resistance to antibiotics in Gram-negative bacilli; particularly gentamicin, quinolone and cephalosporin resistant E. coli. This is of concern as E coli is the most common cause of community and hospital acquired Gram-negative sepsis. Local surveillance has identified the following risk factors for multi- resistant E coli sepsis : Recurrent urinary or biliary tract sepsis particularly where multi-resistant isolates have been previously identified from clinical specimens. Recent treatment with a quinolone antibiotic eg ciprofloxacin. To enable effective management of these patients, it is therefore important that appropriate specimens (including blood cultures) are taken and their previous microbiology reviewed. Where a multiresistant isolate has been identified previously eg gentamicin resistant coliform in urine, first line therapy must be discussed with a medical microbiologist, as the following first line guidance may not be appropriate.
Nottingham Antibiotic Guidelines Committee -2 -
Oct 2004
Review Oct 2006
Guidance on Initial Antibiotic Therapy by Body Site
ABDOMINAL INFECTION (see note regarding multi-resistant Gram negative bacilli on page 2 above) eg perforation of abdominal / gynaecological viscus – which is usually polymicrobial. Cefuroxime IV 1.5g tds (not to be used in serious penicillin allergy –e.g. anaphylaxis) + Metronidazole IV 500mg tds or PR 1g tds for 3 days then bd plus if in septic shock: single dose Gentamicin IV 5 mg/kg (max 500mg) [See dosing advice and renal impairment page 9-10] OR if C. difficile is a problem in the patient or an endemic problem in the ward/ hospital e.g. medical wards at CHN and the patient is not penicillin allergic: Ampicillin IV 1g qds + Metronidazole IV 500mg tds or PR 1g tds for 3 days then bd + single dose Gentamicin IV 5 mg/kg (max 500mg) [See dosing advice and renal impairment page 9-10]
BILIARY SEPSIS (see note regarding multi-resistant Gram negative bacilli on page 2 above) Cefuroxime IV 1.5g tds (not to be used in serious penicillin allergy –e.g. anaphylaxis) + Metronidazole IV 500mg tds or PR 1g tds for 3 days then bd plus if in septic shock: single dose Gentamicin IV 5 mg/kg (max 500mg) [See dosing advice and renal impairment page 9-10] OR if severe: Ciprofloxacin IV 400 mg bd after discussion with a medical microbiologist + Metronidazole IV 500 mg tds or PR 1g tds for 3 days then bd plus if in septic shock: single dose Gentamicin IV 5 mg/kg (max 500mg) [See dosing advice and renal impairment page 9-10]
Nottingham Antibiotic Guidelines Committee -3 -
Oct 2004
Review Oct 2006
Guidance on Initial Antibiotic Therapy by Body Site BONE AND JOINT Joint aspiration/specimen of pus for Gram stain and culture (prior to treatment if possible) is mandatory to establish the diagnosis and further management. If unable to obtain a specimen contact the on-call rheumatologist/orthopaedic surgeon. Flucloxacillin IV 2g qds (covers both sensitive S. aureus and streptococcal infections) OR
Cefuroxime IV 1.5g tds if suspected/proven Gram negative infection, elderly patients and/or immunocompromised. (not to be used in serious penicillin allergy –e.g. anaphylaxis)
If MRSA infection is a possibility (see page 2) discuss with the duty medical microbiologist. If flucloxacillin-sensitive S aureus infection: Flucloxacillin IV 2g qds + Sodium Fusidate PO 500mg tds (do NOT use alone) If suspected/proven gonococcal infection: Ceftriaxone IV 1g od until sensitivities known (increasing resistance locally to penicillin and quinolones). Penicillin-allergy: Clindamycin IV 600mg qds
IV CANNULA SEPSIS Usually due to Staphylococcus aureus sepsis, 40% of which are resistant to flucloxacillin (MRSA). Vancomycin IV 1g bd (If mild renal impairment or age >65 years, reduce frequency to 1g od - see page 8) Change to Flucloxacillin if a S. aureus sensitive to flucloxacillin is isolated (MSSA). Cont….
Nottingham Antibiotic Guidelines Committee -4 -
Oct 2004
Review Oct 2006
Guidance on Initial Antibiotic Therapy by Body Site …Cont
If pus at site of an old venflon site but no signs of sepsis: Doxycycline PO 100 mg bd for one day then 100mg od for 6 days which is active against nearly all MRSA and sensitive S.aureus isolates. Monitor line site closely to check response to treatment, and send blood cultures and swab of pus prior to initiating treatment. (Change to Flucloxacillin if S.aureus sensitive to flucloxacillin is isolated (MSSA)).
CELLULITIS Therapy is usually directed at Streptococcus pyogenes (group A -haemolytic streptococcus) and S aureus When mild: Flucloxacillin PO 500mg qds (for penicillin allergy: Erythromycin PO 500mg qds). When severe: Community acquired Flucloxacillin IV 2g qds (covers both S aureus and S pyogenes). Hospital acquired / Re-admission/Known MRSA colonisation Vancomycin IV 1g bd (If mild renal impairment or age >65 years, reduce frequency to 1g od - see page 8) Penicillin allergy: Clindamycin IV 600mg qds OR if possibility of MRSA: Vancomycin IV 1g bd (renal dose – see above) Unresponsive infection If rapidly progressive cellulitis with shock, please discuss with a medical microbiologist as the addition of clindamycin may be warranted and the possibility of deeper infection, particularly necrotising fasciitis should be considered, which is a surgical emergency. Unresponsive infection may be due to another diagnosis eg varicose eczema, when a dermatology opinion may be appropriate.
Nottingham Antibiotic Guidelines Committee -5 -
Oct 2004
Review Oct 2006
Guidance on Initial Antibiotic Therapy by Body Site INFECTIVE ENDOCARDITIS It is essential to collect three sets of blood cultures, from separate sites (20ml per set) before treatment. NOTE: All therapy and investigation should be discussed with Microbiology/Infectious Diseases. Therapy is determined by positive microbiology results or the likely causative organism and is advised by microbiology – please see separate guidance available on the antibiotic websites: QMC: http://intranet/antibiotics CHN: http://citynet/antibiotics MENINGITIS
See separate guidelines.
PNEUMONIA
See separate guidelines.
UROSEPSIS (but see note regarding multi-resistant gram negative bacilli on page 2) Pyelonephritis is usually due to Gram negative bacilli Cefuroxime IV 1.5g tds (not to be used in serious penicillin allergy –e.g. anaphylaxis) plus if in septic shock: single dose Gentamicin IV 5 mg/kg (max 500mg) [See dosing advice and renal impairment page 9-10] OR
if C. difficile is a problem in the patient or an endemic problem in the ward/hospital e.g. medical wards at CHN and not penicillin allergic: Ampicillin IV 1g qds + single dose Gentamicin IV 5 mg/kg (max 500mg) [See dosing advice and renal impairment page 9-10]
OR if patient is penicillin allergic: and C difficile is a problem in the patient or an endemic problem in the ward/ hospital eg medical wards at CHN Ciprofloxacin PO 500mg bd or if vomiting: IV 400mg bd after discussion with duty medical microbiologist plus if in septic shock: single dose Gentamicin IV 5 mg/kg (max 500mg) [See dosing advice and renal impairment page 9-10] Nottingham Antibiotic Guidelines Committee -6 -
Oct 2004
Review Oct 2006
Guidelines for Empirical Treatment of Suspected Severe Infection where MRSA is a Possibility
Previous MRSA infection / colonisation Inpatient > 48 hours Recent treatment as an inpatient in the last 6/12 or outpatient with an indwelling line Patient with long term urinary catheter Nursing / residential home patient with breaks in skin
YES
NO
Likely S.aureus Sepsis? e.g. Line infection Osteomyelitis Septic arthritis Skin sepsis
YES Vancomycin IV 1g bd † * Re-evaluate after 48 hrs. If not MRSA change to flucloxacillin
If in doubt discuss with a medical microbiologist/ on-call infectious disease consultant
Likely S. aureus Sepsis? e.g. Osteomyelitis Septic arthritis Skin sepsis
YES
NO
Flucloxacillin IV 1-2g qds*
Cefuroxime IV 1.5g tds + Gentamicin IV 5mg / kg (up to a maximum of 500mg) as a single dose (see dosing advice and renal impairment pages 9-10) with microbiological review prior to further doses being given.
When blood cultures are taken two pairs of bottles each from two venepuncture sites should be sent to microbiology. In hours, the samples should be sent straight to microbiology. Out of hours, the two sets should be taken to the incubator on A-floor at QMC or the incubator at pathology reception or medical admissions at CHN. Blood cultures must not be sent by the airtube system. Nottingham Antibiotic Guidelines Committee -7 -
NO
Oct 2004
Cefuroxime IV 1.5g tds *
* Add Gentamicin 5mg / kg (max. 500mg )as a single dose if in septic shock, (see dosing advice and renal impairment pages 9-10) with further microbiological review prior to further doses being given. † Vancomycin 1g od if> 65 years or with mild renal impairment (see page 8).
Review Oct 2006
VANCOMYCIN DOSING AND MONITORING Vancomycin is used parenterally for the treatment of resistant Gram-positive infections. Serum monitoring of pre-dose levels is essential to ensure therapeutic levels are achieved without renal toxicity. The normal dose is 1g bd infused over 2 hours. If mild renal impairment or age >65 years, frequency reduced to 1g od. For moderate or severe renal impairment please see separate guidance “Antibiotic doses for adults with renal impairment” Monitoring of levels
A pre-dose sample should be taken before the third or fourth dose aiming for a level of 5-12mg /L. (red topped sample sent to microbiology)
Give time of last dose and time sample taken, details of dose and latest creatinine on the sample request form (without which the result cannot be interpreted)
The dose can be given after the pre-dose level is taken if the serum creatinine is normal with good urine output
It is not necessary to do a post dose level
Try and time the dose so it is convenient for levels
Results will be available on the results reporting system on the day that the sample is received.
Nottingham Antibiotic Guidelines Committee -8 -
Oct 2004
Review Oct 2006
ONCE DAILY GENTAMICIN DOSING AND MONITORING Gentamicin is an effective antibiotic for treating many infections, especially those arising from the gastrointestinal and urinary tract or hospital-acquired pneumonia. Recent studies have shown that gentamicin can be given as a single dose rather than in divided doses. This is easier for the ward staff, requires fewer levels to be taken, and appears to be less nephrotoxic. (The effect on ototoxicity is still unclear.) This regimen is ideal for short courses e.g. 5 days. Longer courses will need conventional dosing. NB It is not appropriate for some patient groups either because of lack of published data, or risk of accumulation and toxicity. Not to be used in:
Children, (Neonates follow separate cross-town NNU guidelines) Cystic fibrosis patients Profound sustained neutropenia (i.e. 5 days) Pregnancy Endocarditis Ascites Major burns (>20% surface area)
Dosage:
Use 5mg/kg/dose (up to a maximum of 500mg except when the dose is advised by pharmacy) Round the dose up or down to the nearest 40mg increment e.g. 320mg or 360mg Give as an infusion over 20-30 minutes (in 100ml NaCl 0.9% or Dex 5%). In patients with established renal impairment (ie GFR