Algorithms and Appendices
Start Smart, Then Focus Care Bundle
Start Smart, Then Focus Care Bundle
Gentamicin Dosing Schedule
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Gentamicin
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General Information |
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Adverse Effects |
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Cautions and Contraindications |
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Endocarditis: 3mg/kg once daily Multiple daily dosing may be warranted in certain instances – please consider consulting Microbiology/Infectious Diseases.
Pregnancy: 3-5mg/kg once daily Please discuss with the microbiology team if needed and see the algorithm Dose Calculations Step 1: Weigh patient (kg) to determine Actual Body Weight. Record height. Step 2: Calculate the Body Mass Index and/or Ideal Body Weight to determine if the patient is obese. (Please see formula for weight calculation) Step 3 : Obese Dosing Weight/Adjusted Body Weight should be used in CrCl and dose calculations if BMI >30 kg/m 2 or Actual Body Weight is 20% more than Ideal Body Weight. (Please see formula for weight calculation) Step 4: Calculate Creatinine clearance using Cockcroft-Gault equation using either Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight as indicated above. The Cockcroft Gault formula is less reliable in children, acute renal failure, oedematous states, muscle wasting, amputees, and malnourished patients. (Please see MdCalc Creatinine Clearance Calculator) Step 5: Calculate the gentamicin dose to be administered based on CrCl AND weight (Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight) as per the table below.
Monitoring and Dose Adjustment
References
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Gentamicin Dosing Algorithm
Gentamicin Dosing Algorithm
Step 1: Select Patient Appropriately
For empiric therapy (pathogen not known), use Amikacin instead of Gentamicin in patients with:
- A history of gentamicin resistant gram negative pathogens (review previous microbiology test results).
- Sepsis requiring ICU review/admission, or septic shock.
- Sepsis when using concomitant ciprofloxacin in patients with IgE-mediated/anaphylaxis/severe penicillin allergy (due to risk of co-resistance)
Cautions : Age ≥65, renal impairment (CrCl <80ml/min), obesity (use obese dosing weight), concomitant nephrotoxins, volume depletion, auditory and vestibular disorders.
Contraindications: Myasthenia gravis
Step 2: Prescribe Dose
Max Gentamicin Daily Dose = 480mg
Obese Dosing Weight should be used in CrCl and dose calculations if BMI >30kg/m 2 or Actual Body Weight is 20% more than Ideal Body Weight.
In oliguria (urine output <500 mL/day), dose as per CrCl <10mL/min.
(Please see formulae for BMI and weight calculations )
(Please see MdCalc Creatinine Clearance Calculator)
Step 3. Order Trough Level
- Order trough level 16-24 hours after first dose
- Ensure request form and serum sample are labelled with date and time of the last dose AND date and time level was taken
- Monitor renal function
Step 4. Check and Interpret Trough Level
Amikacin Dosing Schedule
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Amikacin
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General Information |
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Adverse Effects |
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Cautions and Contraindications |
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Dose Calculations |
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Step 1: Weigh patient (kg) to determine Actual Body Weight and record height. Step 2: Calculate the Body Mass Index and/or Ideal Body Weight to determine if the patient is obese. (Please see formulae for weight calculation) Step 3 : Obese Dosing Weight/Adjusted Body Weight should be used in CrCl and dose calculations if BMI >30 kg/m 2 or if ABW is 20% more than Ideal Body Weight. (Please see formula for weight calculation) Step 4: Calculate Creatinine clearance using Cockcroft-Gault equation using either Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight as indicated above. Use of Cockcroft Gault formula is less reliable in children, acute renal failure, oedematous states, muscle wasting, amputees, and malnourished patients. ( Please see MdCalc Creatinine Clearance Calculator) Step 5: Calculate the amikacin dose to be administered based on CrCl and weight (use Obese Dosing Weight/Adjusted Body Weight if obese) as per the table below.
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Monitoring and Levels |
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References |
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Tobramycin Dosing Schedule
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Tobramycin |
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General Information |
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Tobramycin is an aminoglycoside antibiotic with a narrow therapeutic index. Effective use is complex and should be discussed with Microbiology or Infectious Diseases. Weight-based dosing and therapeutic drug monitoring (TDM) are essential to ensure therapeutic efficacy and to minimise the risk of adverse effects such as nephrotoxicity, vestibular and ototoxicity. Note: risk is increased in renal impairment, in prolonged therapy, in patients receiving higher doses or for those on concomitant nephrotoxic medications. Tobramycin is a restricted antimicrobial which should only be prescribed when it is in line with the recommendations of local antimicrobial guidelines or following discussion with Clinical Microbiology/Infectious Diseases. Once daily dosing of Tobramycin is recommended for most patients. Discuss patients with renal impairment (creatinine clearance <30ml/minute) with Pharmacy/Clinical Microbiology/Infectious Diseases. Use dose calculations as outlined below however do not delay 1 st doses in patients requiring urgent therapy if renal function information is not available. Do NOT hold dose while waiting for level to be reported in a patient <65 years with good renal function (creatinine clearance >80ml/minute) and good urine output, unless specifically advised to do so. However, in a patient >65 years, or with abnormal renal function (creatinine clearance <80ml/minute), it is preferable to await the result of the first tobramycin level (i.e. before the second dose) before giving the next dose. If the level is <1mg/L and renal function is stable it is not necessary to routinely hold subsequent doses pending levels. Review need for ongoing treatment with tobramycin on a daily basis - courses should not usually exceed 3 days, except in cystic fibrosis. Please discuss patients on extended treatment courses of tobramycin with Clinical Microbiology/Infectious Diseases. **** Note: These recommendations do not apply to the use of tobramycin in cystic fibrosis patients - these patients must be discussed with a specialist. **** |
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Adverse Effects |
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Vestibular and ototoxicity can occur independently of serum tobramycin levels and duration of treatment, however the risk increases significantly with higher cumulative doses and courses of longer durations. Nephrotoxicity : Consider renal function, volume status, and the use of concomitant nephrotoxic agents such as NSAIDs, ACE inhibitors, and diuretics, when prescribing aminoglycosides. |
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Cautions and Contraindications |
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Caution is advised in patients with auditory and vestibular disorders, and conditions characterised by muscular weakness. Aminoglycosides (Gentamicin, Amikacin, Tobramycin) are contraindicated in patients with myasthenia gravis as they may impair neuromuscular transmission in these patients. |
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Dose Calculations |
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Step 1: Weigh patient (kg) to determine Actual Body Weight. Record height. Step 2: Calculate the Body Mass Index and/or Ideal Body Weight (IBW) to determine if the patient is obese. ( Please see formula for weight calculation ) Step 3 : Obese Dosing Weight/Adjusted Body Weight should be used in CrCl and dose calculations if BMI >30 kg/m 2 or Actual Body Weight is 20% more than Ideal Body Weight (IBW). ( Please see formula for weight calculation ) Step 4: Calculate Creatinine clearance using Cockcroft-Gault equation using either Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight as indicated above . The Cockcroft Gault formula is less reliable in children, acute renal failure, oedematous states, muscle wasting, amputees, and malnourished patients. ( Please see MdCalc Creatinine Clearance Calculator ) Step 5: Calculate the Tobramycin dose to be administered based on CrCl AND weight (Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight) as per the table below.
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Monitoring and Dose Adjustment |
References
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Teicoplanin Dosing Schedule
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Teicoplanin |
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General Information |
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Cautions and Contraindications |
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Adverse Effects |
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Dosing and Monitoring |
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Dosing is based on weight, clinical indication and renal function (CrCl calculated using Cockcroft & Gault). (Please see MdCalc Creatinine Clearance Calculator) Higher doses are used for deep-seated infections and may also be indicated in severe infections or critical illness. Actual body weight is always used for dose calculations (including where BMI ≤18 and ≥30kg/m 2 ). Dose adjustments in renal impairment do not need to be made until after the 4 th day.
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Vancomycin Dosing Schedule
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Vancomycin |
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Refer to dosing algorithm below |
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Levels |
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Collect predose level before 4th dose of vancomycin. Give the dose. Any adjustments necessary can be made to the 5th dose onwards. Predose level should be between 10- 15μg/ml. (In severe/complicated infection 15-20 μg/ml). If continuing vancomycin and renal function is stable, repeat level twice weekly. Daily levels may be required if renal function is unstable. Note: 1-hour post dose levels are not necessary. Clearly state dose, time of dose and time of blood sample collection on the request form. |
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Comments |
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Must be administered slowly IV at a maximum rate of 10mg/min to avoid reaction such as red man syndrome. In severe/complicated infections a loading dose of 25 mg/kg can be used to facilitate rapid attainment of target trough serum vancomycin concentration. Complicated Infections:
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IV to PO Switch
Many patients are commenced on intravenous (IV) antimicrobials when admitted to hospital. With clinical improvement and when the extent and site of infection become evident, it may be appropriate to DE-ESCALATE e.g. targeted therapy with narrow spectrum agent or SWITCH to an oral route or STOP antimicrobials if infection has resolved or been outruled.
A Start Smart, Then Focus approach is recommended and review antimicrobials at 24-48 hours with culture results. Review patients regularly for suitability for oral switch and apply the criteria below (Table 1).
Antimicrobials with excellent oral bioavailability
Some antimicrobials have excellent oral bioavailability such as:
- Ciprofloxacin
- Clarithromycin
- Clindamycin
- Fluconazole
- Levofloxacin
- Linezolid
If use of these antimicrobials is required, consider the oral route from start of therapy if clinically suitable:
*Higher oral doses may be required in complex/severe infections. Please consult Clinical Microbiologist.
** Please read the HPRA Drug Safety Alert issued in 2018 and the HPRA Drug Safety Newsletter issued in 2023 highlighting restrictions on use of fluoroquinolones (eg. ciprofloxacin, levofloxacin) due to the risk of disabling, long-lasting and potentially irreversible side effects (including tendon damage, QT prolongation, neuropathies and neuro psychiatric disorder). Use of fluoroquinolones in older patients, those with renal impairment, solid organ transplantation or on systemic corticosteroids increases the risk of tendon damage.
Advantages of IV to oral switch include: Reduction of treatment cost, reduction of duration of hospital stay, reduction of the risk of intravascular catheter-associated infections, improved patient comfort, enabling mobility and reduction of nursing and medical time required to administer therapy.
Positive Blood Cultures - Tips on Clinical Assessment of Patients Following Notification of Positive Blood Culture and Gram Stain
Please note that this guide is not comprehensive of all potential pathogens and scenarios for positive blood cultures. It is a simply a guide to aid the attending doctor when assessing the clinical significance and need for urgent action on receipt of a new blood culture gram stain result (verbal / electronic). All empiric therapy should be modified according to definitive identification and sensitivity testing, clinical response and senior consultation.
Each individual case should be taken on its own merits and the clinical assessment of the patient and actions, including prescribing of empiric antimicrobial therapy for newly positive blood cultures remains the responsibility of the attending clinician.
Gram Positive Cocci (GPC)
Gram Positive Cocci (GPC)
Gram Positive Cocci (GPC) - Perhaps the most common gram stain result phoned during the working day or after hours.
Potential GPC organisms (most common):
Staphylococci: ( Staphylococcus aureus (MSSA or MRSA) or Coagulase Negative Staphylococci) Staphylococci often have an appearance of cells in groups or clusters on gram.
Streptococci: (including Group A streptococci or other haemolytic streptococci e.g. Group B/C/G, Streptococcus pneumoniae (pneumococcus), Streptococcus viridans ). Streptococci often have an appearance of cells in pairs or chains on gram stain.
Enterococci: (including Enterococcus faecalis / Enterococcus faecium / VRE if either resistant to vancomycin). Enterococci often have an appearance of cells in chains on gram stain.
Risk assessment
The key is to review the patient carefully for signs and symptoms of sepsis / bacteraemia. Carry out a NEWS score and follow the Sepsis Six protocol if clinically indicated. Bear in mind that the gram stain result may reflect a causative organism of life threatening sepsis ( e.g. MSSA, MRSA, Group A Strep, Streptococcus pneumoniae , Enterococcus spp) or a skin contaminant (e.g. Coag Neg Staph / Strep viridans ), therefore careful clinical risk assessment is paramount. Note it is important not to dismiss potential skin contaminants such as Coagulase Neg Staph / Strep viridans if endocarditis / intravascular catheter or prosthetic device infection suspected.
Empiric Antibiotic Cover
This should be guided by the Gram stain appearance and likely significance / pathogen based on the clinical risk assessment. Consult the current empiric antimicrobial guideline document for advice on empiric cover in the relevant section.
Check previous microbiology results and for a history of MRSA colonisation / infection. If the potential pathogen appears likely from the likely source of sepsis, ensure patient is on appropriate antimicrobial therapy for that source and pathogen (e.g. Group A Strep in severe soft tissue infection / Strep pneumoniae in CAP).
If systemic sepsis suspected, and source and potential pathogen unclear - glycopeptides cover most Gram positive organisms and a loading dose of vancomycin is a reasonable option to cover the patient pending the culture result of ID and sensitivity. It is critically important however that this step is taken only if clinical indication of sepsis or significant infection and that the antimicrobial treatment is later reviewed with the culture identification and sensitivity and assessed regarding the need to continue / stop / change therapy. If the patient is clinically well following a thorough clinical review and contamination is suspected – a watch-and-observe approach is reasonable pending identification and sensitivity on culture. Ensure there is a trigger for a repeat review and initiation of empiric antimicrobial therapy if the patient develops new signs/symptoms.
Gram Negative Bacilli (GNB)
Gram Negative Bacilli (GNB)
Gram Negative Bacilli (GNB) GNB on Gram of blood culture represents presumptive Gram negative septicaemia and the need for urgent review and prompt antibiotic treatment pending confirmation of identification.
Potential GNB organisms (most common):
Enterobacterales including E coli , Klebsiella spp, Enterobacter spp, Pseudomonas spp, Acinetobacter spp, Gram negative anaerobes including Bacteroides (less common) Note that MDRO (Multi-Drug Resistant Organism) including ESBL E coli / Klebsiella , CPE E coli / Klebsiella , MDR Pseudomonas / Acinetobacter are included in this category.
Risk assessment
The key is to review the patient carefully for signs and symptoms of sepsis / bacteraemia. Carry out a NEWS score and follow the Sepsis Six protocol if clinically indicated.
Bear in mind that the Gram stain result of GNB may reflect a causative organism of life threatening sepsis and may harbour antibiotic resistance mechanisms.
Ensure Sepsis Protocols are followed as clinically appropriate. In a very small number of cases GNB on blood culture may turn out to be contaminants (e.g some Acinetobacter / environmental GNBs) but the vast majority are clinically significant and often pathogens of life-threatening sepsis, warranting immediate appropriate antibiotic therapy and source control.
Empiric Antibiotic Cover
Gram negative sepsis requires urgent review and appropriate empiric antibiotic therapy. Consult this document for advice on empiric cover in the relevant section. If the potential pathogen appears likely from the likely source of sepsis ensure patient is on appropriate antimicrobial therapy for that source and pathogen. If source unclear – see Sepsis - Undetermined Origin Section.
Gram Negative Cocci (GNC)
Gram Negative Cocci (GNC)
Gram negative cocci on gram of blood culture represents presumptive Meningococcal Septicaemia and is a medical emergency warranting urgent senior clinical review, supportive therapy and rapid administration of appropriate empiric antimicrobials pending confirmation of identification. Notify Public Health.
The key is to review the patient urgently for signs and symptoms of meningococcal sepsis. The patient may already be on appropriate empiric therapy following the initial clinical assessment if meningococcal sepsis was suspected. Carry out a NEWS score and follow the Sepsis Six protocol if clinically indicated. Ensure Meningococcal Sepsis Protocols are followed and that the patient is on the appropriate antimicrobials and doses. See relevant section in this guideline.
Gram Positive Bacilli (GPB)
Gram Positive Bacilli (GPB)
Potential GPB organisms later confirmed by culture:
“Diphtheroid” bacilli or Coryneforms, Proprionibacteria, Bacillus species, Listeria monocytogenes /spp Anaerobic GPB including Clostridium perfringens , and other Clostridia species
Risk assessment
The key is to review the patient carefully for signs and symptoms of sepsis / bacteraemia.
Carry out a NEWS score and follow the Sepsis Six protocol if clinically indicated. Bear in mind that the gram stain result may reflect a causative organism of life threatening sepsis ( e,g Listeria / Clostridia species ) or more frequently, a skin contaminant (e.g. Diphtheroid bacilli or Bacillus species), therefore careful clinical risk assessment is paramount.
It is important not to dismiss potential skin contaminants such as Diphtheroid bacilli / Bacillus species if endocarditis / intravascular catheter or prosthetic device infection suspected, or if the more uncommon conditions such as Diphtheria / Bacillus anthracis / Bacillus cereus infection suspected on clinical grounds.
Empiric Antibiotic Cover
This should be guided by the gram stain appearance and likely significance / pathogen based on the clinical risk assessment. If Listeria bacteraemia / sepsis suspected – Amoxicillin +/- Gentamicin (in penicillin allergy discuss with microbiology team). If Clostridial bacteraemia / sepsis suspected (e.g in setting of faecal peritonitis / severe wound infection etc) – a broad – spectrum penicillin such as co-amoxiclav / piperacillin – tazobactam (in penicillin allergy discuss with microbiology team). If systemic sepsis is suspected, and source unclear - glycopeptides cover most gram positive organisms and a reasonable option to cover the patient pending identification and sensitivity and follow up with culture and review of antimicrobial therapy.
However if the patient is clinically well following a thorough clinical review and contamination is suspected, – a watch-and-observe approach is reasonable pending ID and sensitivity on culture. Bear in mind that the patient may already be on appropriate antibiotic regimen for their condition. Ensure there is a trigger for a repeat review and initiation of empiric antimicrobial therapy if the patient develops new signs/symptoms.
Yeasts on Gram Stain
Yeasts on Gram Stain
Yeasts on blood culture Gram stain should be always be considered as significant and suggestive of candidaemia (Candida blood stream infection) pending full clinical review and subsequent species identification. Assess the patient for signs and symptoms of candidaemia, carry out a NEWS score and review previous microbiology results for history of candida colonisation.
Review with regards to potential source(s) including intravenous catheters and intra-abdominal infections.
Repeat blood cultures, consider removal of central lines if implicated and organise echocardiogram.
Other life threatening fungaemia such as cryptococcaemia in immunocompromised hosts e.g. HIV should be considered, It is important to note that Cryptococcus appears as a yeast on Gram stain also and clinical correlation is paramount in these settings.
Empiric antifungal cover
Start an echinocandin such as Anidulafungin 200mg stat IV on Day 1 followed by 100mg OD IV on Day 2 and thereafter pending subsequent identification of the presumed Candida species and antifungal sensitivity testing. Where there is suspicion of cryptococcaemia or other fungaemia, please discuss with clinical microbiology for alternative empiric antifungal therapy.
Liaise with clinical microbiology team regarding follow up and assessment for potential de-escalation as part of the clinical review the following day, and for advice on ongoing management such as source control and optimisation of antifungal therapy based on antifungal sensitivity testing and clinical response.
Guidelines for Consultation with the Clinical Microbiology Advisory Team (C-MAT) UHW
The On-Duty Clinical Microbiology Advisory Team (CMAT) can be contacted on the contact numbers provided (9.30 - 17.30 Monday to Friday). A consultant out-of-hours-service is available for urgent clinical advice outside of these hours.
Prior to contacting the team please have the following 3 actions completed:
- Review the Guidelines for Empiric Use of Antimicrobials in Adults – many queries including empiric therapy by condition, treatment algorithms and therapeutic drug monitoring can be answered here.
- Ensure the patients’ previous microbiology results have been reviewed and summarised and available for the consultation.
- Provide the CMAT team member with an ISBAR summary – please see below
C-MAT Consultation Modified ISBAR
Identify
1. Yourself, 2. Patient, Name, MRN, DOB, Ward
Situation
Summarise main issues related to sepsis / infection Include other relevant key issues in presenting complaint
Background
LOS in hospital lead up to this point – course in hospital, procedures done and dates, relevant test results, current antimicrobial therapy
Assessment
Outline relevant details of your clinical assessment– general impression, signs and symptoms, temperature, BP, NEWS score etc.; Laboratory findings – e.g. WCC, CRP, Lactate, RFTs, LFTs; Other such as relevant imaging results (Echo, CT, MRI, Bone Scan, Other)
Results of other relevant investigations available / pending
Recommendations
Based on this consultation, accurately document the further recommendations from the C-MAT team which may include for example:
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Further tests
- Micro (blood cultures, swabs, fluids, tissue, stool, sputum, urine, serology, CSF, other)
- Lab (WCC ,CRP, Lactate, U/E, LFTs, antibiotic drug levels, Other)
- New / Further Imaging (Echo, CT, MRI, Bone Scan, Other)
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Antimicrobial therapy
- Recommendations on antimicrobial therapy, choice of agent(s), dose optimisation, proposed length of treatment.
Other Relevant Guidelines and Documents
1 . South East Regional Orthopaedic Service Antibiotic Prophylaxis Guidelines for Open Fractures
2. Local/National guidelines for treatment of diabetic foot infections including diabetic foot osteomyelitis
3. British National Formulary
4. Summary of Product Characteristics (SPCs) for guidance on dosing, renal and hepatic impairment, adverse drug reactions and interactions.
Penicillin Allergy
* It is important to document exactly what symptoms occurred before deciding if a patient is truly penicillin allergic. Check with Patient / Relatives / GP / Community Pharmacy to clarify the nature of allergic reaction:
- Many patients are misdiagnosed as being Penicillin allergic
- An incorrect diagnosis of penicillin allergy leads to unnecessary avoidance of this relatively non-toxic class of drugs, exposes the patient to potentially more toxic drugs, increases health care costs and contributes to the development of antibiotic resistance.
- Patients are often labelled as having a hypersensitivity reaction when in fact a patient may be experiencing a side effect of penicillin, such as gastrointestinal upset (e.g. nausea, diarrhoea) or headache.
- Other concomitant medicines can also be responsible for triggering a hypersensitivity reaction. Therefore, it is important to consider the timeframe over which the hypersensivity reaction has developed relative to the initiation of different medications.
- Patients who have previously presented with a less severe penicillin allergy (e.g. rash - NB: i.e. Non-severe reaction e.g. mild-moderate rash not on the EM/SJS/TEN spectrum of rash and not requiring hospitalisation ) may be considered to be prescribed cephalosporins/carbapenems if the benefits outweigh the risks of cross reactivity. This is a clinical risk assessment. The potential for an allergic reaction should be monitored and resuscitation equipment available if required.
- Patients who are documented as having experienced a severe reaction (e.g. anaphylaxis) from a penicillin should not be prescribed cephalosporins, carbapenems and other betalactam containing antibiotics where acceptable alternatives available. A risk-benefit assessment may be needed in certain circumstances. Discuss individual case with senior clinician and clinical microbiology team if needed.
- Please see HSE guidelines for Antibiotic Allergy with a special reference to Penicillin and Beta Lactam Allergy for further information: https://www.hse.ie/eng/services/list/2/gp/antibiotic-prescribing/drug-interactions/guidelines-for-antibiotic-allergy-with-special-reference-to-penicillin-and-beta-lactam-allergy.html
Formulae for Ideal Body Weight, Adjusted Body Weight Body Mass Index, and Body Surface Area
Formulae for Ideal Body Weight, Adjusted Body Weight Body Mass Index, and Body Surface Area
Ideal Body Weight and Adjusted Body Weight Calculator
Body Mass Index (BMI) and Body Surface Area (BSA) Calculator
Creatinine Clearance Calculator (Cockcroft-Gault Equation)
Creatinine Clearance Calculator (Cockcroft-Gault Equation)
Creatinine Clearance (Cockcroft-Gault Equation) Calculator