Infection Management Guideline: Empirical Antibiotic Therapy

INDICATIONS FOR IV ROUTE (see IVOST guidelines) SIMPLIFY, SWITCH, STOP and STATE Duration!

Guidance for initial hospital therapy in adults. Specialist units may have separate policies.

STOP AND THINK BEFORE YOU GIVE ANTIBIOTIC THERAPY! Antibiotics are overused particulary in the elderly, patients with urinary catheters or suspected UTIs and in patients with viral or non-infective exacerbations of COPD. Always
obtain cultures and consider delay in therapy unless there is a clear anatomical site of infection with high probability of bacterial aetiology, if sepsis syndrome is present or if there is clinical deterioration. Record indication and SIRS score in case notes.
1. IV antibiotic therapy (including gentamicin where indicated) should be administered within 1 hour of recognition of sepsis or severe infection in the clinical area where the diagnosis SIMPLIFY Use narrow spectrum agents whenever possible. has been made. SWITCH In the absence of +ve microbiology and specific situations (see indications for IV route) 2. Sepsis or severe sepsis or deteriorating clinical condition switch to oral therapy when signs of sepsis are resolving and oral route is not compromised. 3. Febrile with neutropenia/ immunosuppression STOP Observe indicated duration of therapy and stop if alternative non-infectious diagnosis is 4. Specific indications: endocarditis, deep abscess, bronchiestasis, meningitis, CNS infection, bone/joint infection, S.aureus bacteraemia, CF, made. intra-abdominal / biliary sepsis infection. RECORD INDICATION, SEPSIS CRITERIA AND DURATION FOR ANTIBIOTIC IN NOTES 5. Skin and soft tissue infection: IV therapy if sepsis or ≥ 2 of heat, erythema, induration/ swelling (usually IV for 48-96 hours) CRP- does not reflect the severity of infection and may remain elevated when the infection is resolving. 6. Oral route compromised: nil by mouth, reduced GI absorption, mechanical It cannot be used, in isolation, to assess the severity of infection and hence the need for IV therapy. swallowing disorder, unconscious, no oral formulation, vomiting

DEFINITION OF SEPSIS (Systemic Inflammatory Response Syndrome (SIRS)) - PLEASE RECORD IN CASE NOTES
Clinical symptoms of infection (sweats, chills, malaise, rigors etc) PLUS 2 or more of the following: • Temp <36° or >38°, HR >90bpm, RR >20/min and WCC <4 or >12 x109/L • Severe sepsis: Sepsis + Organ dysfunction/ hypoperfusion eg. oliguria or urine <40ml/hr, confusion, lactic acidosis or hypotension (eg. systolic BP <90mmHg or reduction of 40mmHg from baseline) NB. Signs of sepsis may be masked in immunosuppression, the elderly and in the presence of anti-inflammatory drugs or beta-blockers. Culture Blood Collect 2 or more (8-10mls each bottle) and appropriate area ie. Urine, sputum, CSF, wound or venous access site
Clostridium difficile infection is associated with prescribing of; Cephalosporins, Co-amoxiclav, Clindamycin, Quinolones (Ciprofloxacin, Levofloxacin, Moxifloxacin, Ofloxacin) and Piperacillin + Tazobactam. These agents must be restricted to reduce selection pressure Gastric acid suppression may predispose the patient to Clostridium difficile. Stop gastric acid suppressive therapy if possible.

Lower respiratory tract Pneumonia
CURB 65 score: Confusion (new onset), Urea >7mmol/L, RR≥30/min, BP diast ≤60 or syst BP<90, Age ≥65 yrs

Skin / soft tissue Mild soft tissue infection
Flucloxacillin 1g 6hrly or if true penicillin allergy Doxycycline 100mg 12hrly or *Clarithromycin 500mg 12hrly Duration 7 days

Gastro-intestinal Gastroenteritis

Urinary tract UTI Prophylaxis in women > 3 UTIs per year

Bone / joint infection
Septic arthritis / osteomyelitis Consider underlying metal work, recent surgery, risk factors for MRSA Consider orthopaedic referral Diabetic foot sepsis Assess ulcer, probes to bone, neuropathy, peripheral vascular disease, MRSA risk? For outpatient therapy consult diabetic clinic guidelines Obtain synovial fluid / deep tissue as appropriate when possible IV therapy usually Septic arthritis / osteomyelitisNative joint IV Flucloxacillin 2g 6hrly + IV Gentamicin** or if true penicillin allergy or IV Vancomycin** + IV Gentamicin** Prosthetic joint IV Vancomycin** + IV Gentamicin** + oral Rifampicin t ≤ 70kg 450mg 12 hrly ≤ 70kg 600mg 12 hrly ( oral sodium fusidate if Rifampicin not suitable) Diabetic foot osteomyelitis as above PLUS oral metronidozle 400mg 8hrly Total duration (IV/oral) dependent on surgical intervention. Usually 6 weeks.

CNS infection

Immunocompromised patient Urgent IV therapy

Severe systemic infection? source

EXAC of COPD / LRTI
Antibiotics if purulent sputum. Oral therapy usually. Dual therapy not recommended Amoxicillin 500mg 8hrly or Doxycyline 200mg stat then 100mg daily or *Clarithromycin 500mg 12hrly Duration 5 days

No antibiotic usually required
Clostridium difficile Infection (CDI): Treat before laboratory confirmation, if suspected CDI (loose stools plus recent antibiotics or hospitalisation). Discontinue if toxin negative Stop / simplify concomitant antibiotics and gastric acid suppressive therapy if possible. Severity markers; colonic dilatation >6cm, WCC >15 x109/L, Creatinine >1.5 x baseline, temp > 38.5°C or immunosuppresion 0-1 severity markers; oral Metronidazole 400mg 8hrly ≥ 2 Severity markers or no improvement after 5 days of metronidazole
oral Vancomycin 125mg 6 hrly (if ileus or hypotension add IV Metronidazole 500mg 8hrly and request surgical review. Continue IV Metronidazole until ileus resolves)

Non-severe communityacquired pneumonia (CAP)
CURB 65 score: 0-1 Amoxicillin 500mg 8hrly or if true penicillin allergy or atypical suspected Doxycycline 200mg stat then 100mg daily or *Clarithromycin 500mg 12hrly Duration 7 days CURB 65 score: 2 (and no sepsis) Amoxicillin 500mg 8hrly + *Clarithromycin 500mg 12hrly Duration 7 days

Mild human or animal infected bite or peri-anal infection
Co-amoxiclav 625mg 8hrly or if true penicillin allergy Doxycycline 100mg 12hrly + Metronidazole 400mg 8hrly Duration 7 days

Cranberry products can prevent recurrent infections in women. Consider a trial of cranberry then. Trimethoprim 100mg 24hrly or Nitrofurantion 50mg 24hrly Give at night Inform G.P. if prophylaxis commenced as inpatient. Long term nitrofurantion prophylaxis may be associated with pulmonary toxicity.

IV therapy to be administered URGENTLY on arrival at hospital and after blood cultures. CT scan before LP if age >60, seizures, reduced GCS, CNS signs or immunosuppression. Seek ID / microbiology advice.

Which patient?
Chemotherapy within 3 weeks, high dose steroids (prednisolone>15mg/day for >2 weeks), other immunosuppressive agents (e.g. anti-TNF, cyclophosphamide), neutrophil <0.5 or < 1.0 and falling AND temp > 38°C or < 36°C on 2 occasions 30mins apart. primary immunodeficiency, NB. For patients with HIV infection please discuss with the ID Brownlee Centre.

Review all anatomical systems Hospital vs community-acquired infection? E.coli, Staph aureus and Pneumococcus are commonest community blood culture isolates Consider MRSA infection – healthcare associated sepsis, recent hospital discharge, postoperative wound or line-related sepsis or sepsis in previous or current MRSA carrier. Consider severe Streptococcal sepsis – e.g. pharyngitis, erythroderma, hypotension.

Bacterial Meningitis
Always refer to senior staff IV Ceftriaxone 2g 12hrly + IV Dexamethasone* 10mg 6hrly (for 4 days) If age ≥ 50 years, immunosuppressed, pregnant or if listeria meningitis suspected add in IV Amoxicillin 2g 4hrly to above If penicillin resistant, pneumococcus suspected add IV Vancomycin** If true penicillin allergy IV Choramphenicol 1g 6hrly +Dexamethasone* then seek ID / microbiology advice. Duration 7 days (meningococcal), 14 days (pneumococcal), 21 days (listeria). Possible viral encephalitis
Aciclovir 10mg/kg 8hrly (see prescribing guidance for dosage alteration in renal impairment) Discuss management with ID. May require repeat LP or neuro-imaging to establish diagnosis. If HSV/VSV confirmed continue therapy for 14-21 days IV (no oral switch)

Lower UTI / cystitis in non pregnant women
Antibiotics if; urinary symptoms, frequency, dysuria. Obtain urine culture. Nitrofurantoin 50mg 6hrly or Trimethoprim 200mg 12hrly Duration 3 days

Sepsis syndrome

* Clarithromycin is known to have serious drug interactions and may prolong the QTc interval. Avoid in patients with other risk factors for QTc prolongation.See BNF (appendix 1) or contact pharmacy for details

No definable site of infection Patients on high dose steroids or severely immunocompromised may not have an increased temperature but present with low blood pressure, hypothermia and or rigors.

Neutropenic plus sepsis
IV Piperacillin + Tazobactam 4.5g 6hrly + IV Gentamicin**
Consider Staphylococcal infection (e.g. linerelated sepsis or soft tissue infection)

Source unknown
IV Benzylpenicillin 1.2g- 2.4g 6hrly + IV Flucloxacillin 2g 6hrly + IV Gentamicin** if true penicillin allergy
IV Vancomycin** + IV Gentamicin** if streptococcal infection suspected ADD IV Clindamycin 600mg 6hrly (up to 1200g 6hrly) + seek ID/ microbiol-

Lower UTI in men (without sepsis)
Send urine for culture Nitrofurantoin 50mg 6hrly or Trimethoprim 200mg 12hrly

ORAL THERAPY USUALLY RECOMMENDED
Severe / complicated infective EXAC of COPD
Use IV therapy if indication for IV route (see above) or ventilation required or sepsis. IV Amoxicillin 1g 8hrly or IV *Clarithromycin 500mg 12hrly Duration 7 days (IV/oral) NB. Doxycycline not available IV.

Total duration 10-14 days
Ensure adequate hydration

Severe CAP
CURB 65 score: ≥3 or CAP PLUS sepsis syndrome: IV or oral *Clarithromycin 500mg 12hrly and either IV Amoxicillin 1g 8hrly or IV Co-amoxiclav 1.2g 8hrly (if previous treatment in the community) or if true penicillin allergy IV *Clarithromycin 500mg 12hrly + IV Vancomycin
Total duration 7-10 days (IV/oral) or up to 14 days if atypical suspected or bacteraemia

Duration 7 days

Moderate to severe cellulitis / erysipelas
IV Flucloxacillin 1-2g 6hrly + / - IV Gentamicin** if severe or if true penicillin allergy IV Vancomycin** + / - IV Gentamicin** if severe Total duration 10 days (IV/oral)

Intra abdominal sepsis
IV Amoxicillin 1g 8hrly + IV Metronidazole 500mg 8hrly + IV Gentamicin** or if true penicillin allergy IV Vancomycin** + IV Metronidazole 500mg 8hrly + IV Gentamicin**
Billary tract infection as above; Metronidazole not required unless severe. Pancreatitis does not require antibiotic therapy unless complicated by gallstones Total duration 7 days (IV/oral), but dependent on clinical review

ADD IV Vancomycin** or if true penicillin allergy IV Vancomycin** + IV Gentamicin** + IV Ciprofloxacin 400mg 12hrly If haematology/oncology patient discuss with appropriate specialist and seek ID / microbiology advice. If stem cell / solid organ transplant or acute leukaemia and associated shock give IV Meropenm + IV Amikacin (see Neutropenic Sepsis in Cancer patients poster for details) Immunocompromised patients with fever and no neutropenia Manage as per infection management guidelines based on anatomical source

Upper UTI in non pregnant women and men (without sepsis) Trimethoprim 200mg 12hrly if resistant organisims suspected

ogy advice

Co-amoxiclav 625mg 8hrly Duration 14 days
or if true penicillin allergy Ciprofloxacin 500mg 12hrly Duration 7 days

Healthcare associated infection including possible MRSA infection IV Vancomycin** + IV Gentamicin**
Possible infective endocarditis
Consider if IVDU, line related sepsis, or recent dental extraction always seek senior specialist advice. Native valve IV Amoxicillin 2g 4hrly + IV Flucloxacillin 2g 4hrly + IV Gentamicin** (synergistic dosing) (if true penicillin allergy IV Vancomycin**) + IV Gentamicin** (synergistic dosing) Prosthetic valve IV Vancomycin** + IV Gentamicin** synergistic dosing + oral Rifampicin t ≤ 70kg 450 12hrly > 70kg 600g 12 hrly (oral sodium fusidate if nfampian not suitable)
NB discuss gentamicin dosing + duration with pharmacy and microbiology.

Gentamicin must not be continued beyond 3 or 4 days. Discuss alternative with mircobiology / ID.

Hospital-acquired pneumonia ≤ 4 days of admission
Treat as for CAP using CURB 65 / sepsis criteria

Aspiration pneumonia

Severe human or animal infected bite or peri-anal infection
IV Co-amoxiclav 1.2g 8hrly or if true penicillin allergy IV Metronidazole 500mg 8hrly + IV *Clarithromycin 500mg 12hrly + IV Gentamicin** Total duration 10 days (IV/oral)

Pyelonephritis with sepsis or oral route compromised
IV Amoxicillin 1g 8hrly + IV Gentamicin** or if true penicillin allergy

t Rifampicin is known to have serious drug interactions. see BNF (appendix1) or contact pharmacy for details.

Duration 7 days (IV/oral) ≥ 5 days admission Duration 7 days ≥ 5 days admission

IV Metronidazole 500mg 8hrly and either IV Amoxicillin 1g 8hrly or IV *Clarithromycin 500mg 12hrly Duration 7 days (IV/oral)

**Gentamicin/ Vancomycin**

Avoid Gentamicin in patients with decompesated liver disease, contact microbiology or ID for advice 7. If Creatinine not available give gentamicin as follows, Actual weight Gentamicin Dose < 40Kg 5mg / kg, 40-49kg 240mg, 50-59kg 280mg, 60-69kg 320mg, 70-79kg 360mg, ≥80kg 400mg. 8. If CKD5 give 2.5mg/kg (maximum 180mg) 9. For gentamicin take a sample 6 -14 hrs after the start of the first infusion and review frequency once creatinine and concentration are known.

Spontaneous bacterial peritonitis
Chronic liver disease with ascites and peritoneal white cell count > 500/mm3 or >250 neutrophils/mm3 IV Co- amoxiclav 1.2g 8hrly

IV Gentamicin**

Total duration 14 days (IV/oral)

monotherapy

CURB 65 score: ≤ 2 and no sepsis Oral Doxycycline 100mg 12 hrly

Catheter-related UTI

CURB 65 score: ≥ 3 or sepsis syndrome IV Co-amoxiclav 1.2g 8hrly + IV Gentamicin** if MRSA suspected add IV Vancomycin** or if true penicillin allergy IV Vancomycin** + IV Gentamicin**
Total duration 7 -10 days (IV/oral) or up to 14 days if atypical suspected or bacteraemia

Suspected necrotising fasciitis or severe or rapidly progressive infection
IV Flucloxacillin 2 g 6 hrly + IV Gentamicin** + IV Clindamycin 600mg 6hrly IV (up to 1200mg 6hrly) AND CONSIDER EARLY DEBRIDEMENT/ EXPLORATION / SURGICAL REFERAL If IVDU or diabetic or wound involving abdomen / perineum add in IV Metronidazole 500mg 8hrly. If hospital acquired consider MRSA and ADD IV Vancomycin** Discuss with microbiology / ID before changing to oral

if true penicillin allergy IV or Oral Ciprofloxacin 12hrly + IV Vancomycin**
Total duration 7 -10days (IV/oral), but dependent on clinical review

Remove / replace catheter and culture urine. Give single dose of IV Gentamicin** Further antibiotic treatment may not be required. However: - If sepsis or deterioration treat as for pyelonephritis. Total duration 7 days (IV/oral)

1. To access dose calculator click on clinical info on staff intranet page and go to antimicrobial guidelines. 2. Check creatinine / renal function daily. 3. Record accurate times of dose administration and concentration measurement. 4. Contact pharmacy if advice required. 5. Do not use Gentamicin beyond 3 or 4 days unless on advice of mircobiology or ID. 6. Ototoxicity is associated with prolonged use of gentamicin. If the patient reports tinnitus, dizziness, poor balance, hearing loss, seeing objects oscillating, stop Gentamicin and contact Micro / ID.

NB. Nitrofurantoin; avoid if CrCl <20ml/min or G6PD deficient

SEVERE INFECTIONS or INFECTIONS WHERE IV THERAPY IS USUALLY RECOMMENDED

Review Antibiotic therapy DAILY: Stop? Simplify? Switch?

RATIONALISE ANTIBIOTIC THERAPY when microbiology results become available or clinical condition changes. Review IV therapy daily and remember IV-ORAL SWITCH NB. Recomended doses are based on normal renal / liver function, see BNF for dose adjustments in renal / liver impairment.

FURTHER ADVICE Can be obtained from the Duty Microbiologist or Clinical Pharmacist or the ID Unit (Brownlee Centre), Gartnavel General Hospital, or your local Respiratory Unit (for pneumonia) or Therapeutics handbook. Infection Control advice may be given by the duty microbiologist.
Greater Glasgow & Cyde Antimicrobial Utilisation Committee, ADTC. August 2012 expires Aug 2014. Review updates on .www.ggcformulary.scot.nhs.uk/Guidelines MIS 165760/a.

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