Appendices

Overview of Common Antibiotics

Β-LACTAMS

Penicillins, cephalosporins, monobactams and carbapenems have a β-lactam ring in their molecular structure. These bactericidal antibiotics act primarily on the bacterial cell wall. Although some bacteria produce β-lactamases and therefore have developed resistance, these drugs on the whole remain useful in treating many different types of infections.

Penicillins

Penicillin is active against Streptococci spp., Neisseria, Spirochaetes, some anaerobes including Clostridia and a few other organisms. Most Staphylococcus aureus isolates are intrinsically resistant to penicillin and there is growing resistance to cloxacillin. The prevalence of penicillinase-producing Neisseria gonorrhoeae is on the increase. There are reports of decreased susceptibility of pneumococci and streptococci to penicillin from other parts of the world. The only serious disadvantage of penicillins is the potential for hypersensitivity reaction.

A. Penicillins

Benzylpenicillin (also known as crystalline penicillin or penicillin G)
- For intravenous (IV) use and needs to be given frequently (4-6 hourly).
Procaine Penicillin
- Intramuscular (IM) preparation with a longer duration of action. Needs to be administered less frequently i.e. daily.
Benzathine Penicillin
- Intramuscular preparation, providing low levels of penicillin in the circulation for 3-4 weeks.
Phenoxymethyl Penicillin (also known as penicillin V)
- An oral preparation, intrinsically less active than Benzylpenicillin.

Penicillin is the drug of choice for the treatment of the following infections:

Streptococcal infections e.g. tonsillopharyngitis
Infections due to Streptococcus pneumoniae
Meningococcal infections e.g. meningitis, septicaemia
Syphilis
Clostridial infections, Diphtheria
Leptospirosis

B. Aminopenicillins

Ampicillin and amoxicillin are destroyed by staphylococcal β-lactamases but have a slightly broader spectrum than penicillins because of their activity against some Gram-negative bacilli such as E. coli, Salmonella spp. and Shigella spp. They also have better activity against H. influenzae and enterococci compared with penicillin.

Although previously sensitive, resistance to these drugs among E. coli is now widespread. Many strains of H. influenzae also produce β-lactamases, which can destroy these drugs.

Amoxicillin is better absorbed than ampicillin and has a longer half-life and hence is preferred for oral therapy. These drugs are used in the empirical treatment of respiratory infections and in the treatment of susceptible urinary tract infections. They may also be used for typhoid fever.

C. Anti–Staphylococcal Penicillins

These are narrow spectrum penicillins, resistant to Staphylococcal β-lactamases. Methicillin, oxacillin, and cloxacillins fall into this category. Of these, only cloxacillin, flucloxacillin and dicloxacillin are clinically useful and are to be used only for proven or suspected staphylococcal infections.

Cloxacillin, suitable for oral administration, can cause cholestatic jaundice in some patients.

Some Staphylococci have developed resistance to this group, by mechanisms other than β-lactamase. These methicillin-resistant Staphylococcus aureus (MRSA) will be resistant to all other β-lactams (i.e. all penicillin, ceph- alosporins, monobactams and carbapenems).

D. Anti–Pseudomonal Penicillins

These are newer penicillins with a high grade of activity against Gram-negative bacteria including pseudomonas, e.g. piperacillin, ticarcillin

E. β-lactam and β-lactamase inhibitor combinations

Examples of β lactamase inhibitors include clavulanic acid and sulbactam.

Amoxicillin can be combined with clavulanic acid, which itself has minimal antibacterial activity but inhibits β-lactamase effectively so that amoxicillin can still be used against β-lactamase-producing bacteria. Amoxicillin/clavulanic acid combination can cause cholestasis. Combinations utilising sulbactam are more expensive and so should be used only while treating infections with known β-lactamase producers.

Note: Hypersensitivity to any penicillin implies the potential for hypersensitivity to all penicillins. See Beta-lactam Allergy below.

Cephalosporins

The cephalosporins have been traditionally divided into “generations” based on their spectrum of activity. In general, cephalosporins are less prone to hypersensitivity reactions, are more stable to staphylococcal penicillinases and have a broader spectrum than penicillins. However, they have very little action against enterococci. None of the cephalosporins available in Timor-Leste have action against MRSA. Cephalosporins also have been shown to select out MRSA, vancomycin-resistant enterococci, and ceftriaxone-resistant Gram-negative bacilli. Therefore, indications for their use should be limited.

First generation cephalosporins include cephalexin (oral), cephalothin and cephazolin (parenteral). The spectrum of activity is similar for each, being effective against penicillinase-producing Staphylococci and other Gram-positive cocci (except MRSA and enterococci) and a few Gram-negative enteric bacilli. There is no special advantage for any one first generation cephalosporins over another. They are not usually the first choice for any infection, although are the first choice for most surgical prophylaxis. They may be used in some patients with penicillin hypersensitivity, see Beta-lactam Allergy below.
Second generation cephalosporins include (among others) cefuroxime and cefaclor (oral). These are more stable to some Gram-negative β-lactamases. Their activity against Gram-positive organisms is similar to, or less than, that of the first generation cephalosporins and they have varying degrees of activity against anaerobes. These drugs have a limited role in therapy and are more expensive than the first generation cephalosporins.
The major activity of the third generation cephalosporins (e.g. ceftriaxone, ceftazidime, cefotaxime) is against Gram-negative bacilli. They have some activity against Gram-positive cocci and their activity against anaerobes varies. A major advantage of these agents is their ability to reach the central nervous system. Ceftazidime has the additional benefit of specific anti-pseudomonal activity. Ceftriaxone and cefotaxime are useful in hospital-acquired and any other Gram-negative septicaemia and meningitis.

Monobactams (e.g. Aztreonam) and Carbapenems (e.g. Meropenem)

Aztreonam is active against Gram-negative bacteria including pseudomonas and β-lactamase-producing Enterobacteriaceae.
Carbapenems have a much broader spectrum, including Gram-positive, Gram-negative and some anaerobic bacteria. They are the agents of choice for ESBL (extended spectrum β-lactamase-producing organisms).

Aminoglycosides

This group of antibiotics (including gentamicin, tobramycin, amikacin, and streptomycin) act by inhibiting protein synthesis in bacteria. They have good activity against aerobic Gram-negative bacilli, including Brucella. When given together with penicillins, they have good activity against Enterococci. Streptomycin in combination is also useful against mycobacteria. Aminoglycosides are not absorbed when given orally and should be administered parenterally for systemic effects. Aminoglycosides are ototoxic and nephrotoxic. The therapeutic index is low and blood levels need to be monitored if used for either directed or empirical therapy for longer than 3 days (see Aminoglycoside dosing below). Despite this disadvantage, they are used widely for their action on Gram-negative bacilli. Gentamicin is the least expensive and is the aminoglycoside of choice for empirical treatment of Gram-negative infection including nosocomial infections. Due to high gentamicin resistance levels in Timor-Leste amikacin is the preferred aminoglycoside in septic shock.

The primary indication for aminoglycosides is as short-term empirical therapy pending the outcome of investigations. Their value as empirical drugs relates to their rapid bactericidal activity and the comparatively low levels of resistance in many community and healthcare-associated Gram-negative pathogens. When used empirically, no further doses should be given beyond 72 hours and if ongoing empirical IV therapy is required (i.e. an organism is not grown) therapy should be changed to an alternative, less toxic drug such as ceftriaxone.

Aminoglycosides are indicated for directed therapy in only a few circumstances. These include, but are not restricted to:

Infections when resistance to other safer antimicrobials has been shown
Low doses as synergistic treatment for streptococcal and enterococcal endocarditis.

Monitoring plasma concentrations of aminoglycosides is recommended in these patients and should commence on the first dose of directed therapy. See Aminoglycoside dosing below.

Fluoroquinolones

These antibiotics (e.g. ciprofloxacin, norfloxacin, levofloxacin) act by inhibiting DNA synthesis within bacteria. Their greatest activity is against aerobic Gram-negative bacilli including Pseudomonas spp., Haemophilus spp., and Gram-negative cocci such as Moraxella and Neisseria spp. Adverse effects include gastrointestinal side effects, hepatotoxicity, CNS toxicity, prolongation of the QT interval, tendonitis, and tendon rupture. Resistance occurs rapidly, so use should be restricted to where there is no alternative.

Gusmao dos Santos C, Francis J, Guterres J, Janson S, Lopes N, Marr I, et al. HNGV Antibiotic guidelines writing group. Antibiotic guidelines Hospital Nacional Guideo Valadares. Timor-Leste; 2016

Antibiotic Spectra of Activity

The Sanford Guide to Antimicrobial Therapy. Dallas Texas: Antimicrobial Therapy Inc.; 2022

Antibiotics During Pregnancy And Breastfeeding

Antibiotic use during breastfeeding

There are two important issues to consider when prescribing drugs such as antibiotics during breastfeeding; firstly the likely exposure of the drug to the infant and secondly the likely effect the drug may have on milk supply. A risk benefit analysis is warranted. Simple advice can be given such as to feed the infant just before the next dose or alternatively to take the medication just after breastfeeding thus avoiding likely peak milk concentrations.

Antibiotic use during pregnancy

The nature of adverse effects of drug use during pregnancy depends upon the time of exposure. Teratogenicity is a major risk with drug exposure during the 1st trimester, while in the 2nd and 3rd trimesters foetal growth and functional development may be affected.

Category A

Drugs which have been taken by a large number of pregnant women without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.

Category B1

Drugs which have only been taken by a limited number of pregnant women without an increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed. Studies in animals have not shown evidence of an increased risk of foetal harm.

Category B2

Drugs which have only been taken by a limited number of pregnant women without an increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of increased risk of foetal harm.

Category B3

Drugs which have only been taken by a limited number of pregnant women without an increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed. Studies in animals have shown evidence of an increased occurrence of foetal harm, the significance of which is considered uncertain in humans.

Category C

Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible.

Category D

Drugs which have caused, are suspected to have caused, or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects.

Category X

Drugs which have such a high risk of causing permanent damage to the foetus that they should not be used in pregnancy or when there is a possibility of pregnancy.

Antimicrobial	Breastfeeding	Pregnancy Class
Acyclovir	Safe to use	B3
Albendazole	Safe to use	D Teratogenic in several animal species. Human data unavailable.
Amikacin	Safe to use	D Foetal ototoxicity and nephrotoxicity have been reported with use of aminoglycosides, reserve for severe or life-threatening infections.
Amoxicillin	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant.	A
Amoxicillin/ Clavulanic acid	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant.	B1
Amoxicillin	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant.	A
Artemether / Lumefantrine	Safe to use in mothers of infants >5kg. Seek specialist advice in mothers of infants <5kg.	D Suspected to cause serious birth defects when administered during the first trimester.

Antimicrobial	Breastfeeding	Pregnancy Class
Azithromycin	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant. Unconfirmed epidemiologic evidence of increased infantile hypertrophic pyloric stenosis risk in infants during first 2 weeks of breastfeeding, with maternal use of macrolides.	B1
Cefazolin	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant.	B1
Ceftriaxone	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant.	B1
Cefuroxime	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant.	B1
Chloramphenicol	Use alternative antibiotic where possible. If chloramphenicol must be used, monitor infant for adverse events (GI disturbance, adequacy of nursing, cytopaenias).	A Ensure chloramphenicol is not circulating at the time of delivery.
Ciprofloxacin	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant. Avoid breastfeeding 3-4 hours after dose to decrease infant exposure.	B3

Antimicrobial	Breastfeeding	Pregnancy Class
Clarithromycin	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant. Unconfirmed epidemiologic evidence of increased infantile hypertrophic pyloric stenosis risk in infants during first 2 weeks of breastfeeding, with maternal use of macrolides.	B3
Clindamycin	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant. Unconfirmed epidemiologic evidence of increased infantile hypertrophic pyloric stenosis risk in infants during first 2 weeks of breastfeeding, with maternal use of macrolides.	A
Cloxacillin	Safe to use however if an alternative is available, use this to reduce risk of GI side effects in infant.	A
Co-trimoxazole	Safe to use in mothers of full-term, healthy infants. Use alternative antimicrobial in mothers of jaundiced, unwell, stressed, or premature infants to reduce the risk of haemoly- sis. Avoid in mothers of G6PD deficient infants.	C Sulphonamides may cause jaundice and haemolytic anaemia in the newborn.
Doxycycline	Possible risk of dental enamel staining or bone deposition of tetracycline. Avoid prolonged (>21 days) or repeat courses during nursing.	D Safe to use during the first 18 weeks of pregnancy. Use after this period causes tooth discolouration in infant.

Antimicrobial	Breastfeeding	Pregnancy Class
Erythromycin	Safe to use. May cause diarrhoea, candidiasis in infant. Unconfirmed epidemiologic evidence of increased infantile hypertrophic pyloric stenosis risk in infants during first 2 weeks of breastfeeding, with maternal use of macrolides.	A
Ethambutol	Safe to use.	A
Fluconazole	Safe to use.	D Reports of spontaneous abortion and congenital abnormalities in infants of mother treated with single or repeated doses of fluconazole in the first trimester.
Gentamicin	Safe to use.	D Foetal ototoxicity and nephrotoxicity have been reported with use of aminoglycosides, reserve for severe or life-threatening infections.
Isoniazid	Safe to use. Monitor infant for rare adverse effects such as jaundice.	A
Ivermectin	Safe to use.	B3

Antimicrobial	Breastfeeding	Pregnancy Class
Levofloxacin	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant. Avoid breastfeeding 4-6 hours after dose to decrease infant exposure.	C
Meropenem	Safe to use. May cause diarrhoea, candidiasis in infant.	B2
Metronidazole	Metronidazole and its active metabolite are present in detectable levels in breast milk. Consider alternative antibiotic if available or use lower doses of metronidazole if two options are given in guideline. If metronidazole is given as a single 2g dose, consider withholding breastfeeding for 12-24 hours after dose.	B2
Penicillin	Safe to use. May cause diarrhoea, vomiting, candidiasis in infant.	A
Pyrazinamide	Safe to use. Monitor infant for rare adverse effects such as jaundice, hepatitis, arthralgia.	B2
Quinine	Safe to use, except in mothers of infants with G6PD deficiency.	D In toxic doses quinine causes foetal damage including deafness. Its ability to induce uterine contractions increases risk of miscarriage.

Antimicrobial	Breastfeeding	Pregnancy Class
Rifampicin	Safe to use.	C Bleeding has been reported in newborn infants and in mothers after use of rifampicin during late pregnancy. If rifampicin is used in late pregnancy vitamin K should be given to the mother and newborn infant.
Tenofovir (TDF)	Safe to use.	B3
Vancomycin	Safe to use.	B2

Drugs and Lactation Database (LactMed) [internet]. Bethesda (MD): National Library of Medicine (US); 2006. https://www.ncbi.nlm.nih.gov/books/NBK501922/

Gusmao dos Santos C, Francis J, Guterres J, Janson S, Lopes N, Marr I, et al. HNGV Antibiotic guidelines writing group. Antibiotic guidelines Hospital Nacional Guideo Valadares. Timor-Leste; 2016

Therapeutic Goods Administration. Prescribing medicines in pregnancy database [internet]. Canberra: TGA; https://www.tga.gov.au/prescribing-medicines-pregnancy-database

Aminoglycoside Dosing

These guidelines recommend once daily dosing for all indications except endocarditis and some neonatal infections. The required dose depends on lean body weight and renal clearance. The first dose should be given irrespective of renal function.

For initial dosing refer to relevant section of the guidelines. Repeat dosing depends on creatinine clearance (see Creatinine-Clearance calculation below). All regimes below will provide gram negative cover for 72 hours. If empiric gram-negative cover is required beyond 72 hours switch to an alternative antibiotic such as ceftriaxone.

It is essential to obtain creatinine results within 24 hours of starting gentamicin or amikacin. If this is not possible treat patients as for normal renal function, unless they have chronic renal impairment, or a strong suspicion of chronic renal impairment (such as diabetes with complications), in which case treat as for moderate renal impairment.

Plasma concentration monitoring (gentamicin levels) is essential if therapy is expected to continue beyond 72 hours (e.g. treatment for endocarditis). Measure plasma concentration 2-3 times per week, or more frequently if kidney function is changing rapidly or substantially. To measure plasma gentamicin concentration, take blood immediately prior to gentamicin dose to obtain trough level. This should be detectable but less than 0.5-1mg/L; adjust dose frequency to maintain level in this range. Monitor for vestibular and ototoxicity, and monitor renal function.

In sepsis for adults with an estimated creatinine clearance of >60ml/minute use an initial high dose of Gentamicin 7mg/kg, or Amikacin 28mg/kg. After this change to Gentamicin 4-5mg/kg, or Amikacin 16-20mg/kg. In patients with an estimated creatinine clearance <60ml/minute use an initial dose of Gentamicin 4-5mg/kg, or Amikacin16-20mg/kg.

Gentamicin and Amikacin dosing intervals in renal impairment

Estimated Creatinine Clearance	Dosing Interval	Maximum number of doses
>60ml/minute	24 hourly	3 (0, 24, 48 hours)
40-60ml/minute	36 hourly	2 (0, 36 hours)
30-40ml/minute	48 hourly	2 (0, 48 hours)
<30ml/minute	Single dose only	1 (0 hours)

Vancomycin Dosing

The following applies to intravenous vancomycin only.
BID vancomycin dosing is recommended for all patients with normal renal function. Consider a loading dose of 25-30mg/kg in critically unwell adults.

Plasma concentration monitoring (vancomycin levels) should be performed in all patients treated with vancomycin for longer than 48 hours, where possible. For adults with creatine clearance >60ml/minute take blood immediately prior to the 4th vancomycin dose to obtain a trough level. For adults with impaired kidney function take blood immediately prior to the vancomycin dose given 48 hours after the first dose. For patients with creatinine clearance >20ml/minute it is not necessary to wait for the vancomycin level before giving the 48-hour dose. Monitor levels at least weekly in stable patients, and more frequently during dose optimization and if renal function changes. Monitor creatinine 2-3 times a week. For most conditions the target level is 15-20mg/L. When treating CNS infections, a trough of up to 25mg/L may be required. If the vancomycin plasma concentration is outside the target range once steady state has been reached (after 4 doses), adjust the dose. Dosage adjustments should be made in a linear manner; for example in a patient receiving 1g BID, if the level is two-thirds of the target concentration (e.g. 10), then the dose is two-thirds of what it should be, and the dose should be increased by 50%, to 1.5g BID.

In dialysis patients vancomycin should be given in the last 100 minutes of dialysis or after dialysis ends. If vancomycin is given during dialysis give 30-35mg/kg loading dose, and 7.5-15mg/kg subsequent doses (give higher end of range if using a dialyzer with high permeability). If vancomycin is given after dialysis give 25mg/kg loading dose, and 7.5-10mg/kg subsequent doses (give higher end of range if using a dialyzer with high permeability). If vancomycin levels are available blood should be taken immediately prior to haemodialysis. If the level is <15mg/L give dose, if the level is >15mg/L do not give dose but repeat level prior to next haemodialysis session.

To reduce the risk of red-man syndrome, doses should be infused at a rate ≤ 10mg/minute, and the total infusion time should not be less than 1 hour. If red-man syndrome occurs, the infusion should be given more slowly.

Vancomycin dosing for adults and children ≥ 12 years

Creatinine clearance	Dose for weight <40kg	Dose for weight 40- 49kg	Dose for weight 50- 64kg	Dose for weight >65kg
>60ml/minute	15-20mg/kg BID	750mg BID	1g BID	1.5g BID
20-60 ml/minute	15-20mg/kg OD	750mg OD	1g OD	1.5g OD
<20ml/minute	15-20mg/kg 48 hourly	750mg 48 hourly	1g 48 hourly	1.5g 48 hourly

Vancomycin dosing for children <12 years

Age	Dose
Neonate <36 weeks post conception	15mg/kg BID maximum. See Appendix H
Term neonates week 1 of life	15mg/kg BID
Term neonates weeks 2-4 of life	15mg/kg TID
Infants >1 month and children <12 years	15mg/kg (max 750mg) QID

Seek specialist advice for children <12 with impaired renal function.

eTG complete. Principles of vancomycin use. In: Therapeutic Guidelines [digital]. Melbourne: Therapeutic Guidelines Limited; 2019. http://www.tg.org.au

Hallam C, Whitbourn D. Trust Guideline for the use of parenteral vancomycin in adults. Britain: NHS Foundation Trust; 2021

Rybak M, Le J, Lodise T, Levine D, Bradyley J,Liu C et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health-Syst Pharm 2020; 77: 835-864. DOI 10.1093/ajhp/zxaa036

Creatinine Clearance Calculation (Cockcroft-Gault calculation)

Adult males: (140 – age) x ideal weight (kg)
0.814 x serum creatinine (micromole/L)

Adult females: Multiply above equation by 0.85

Renal Dose Adjustment Of Common Antimicrobials In Adults

eTG complete. Renal impairment and antimicrobial dosing. In: Therapeutic Guidelines [digital]. Melbourne: Therapeutic Guidelines Limited; 2019. http://www.tg.org.au

Neonatal Antimicrobial Dosing

eTG complete. Therapeutic Guidelines [digital]. Melbourne: Therapeutic Guidelines Limited; 2019. http://www.tg.org.au

McMullan B, Andresen D, Blyth C, Avent M, Bowen A, Britton P, et al. Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines. Lancet Infect Dis 2016; 16(8):e139-152. doi: 10.1016/S1473-3099(16)30024-X

Royal Hospital for Women. Australasian Neonatal Medicine Formulary [internet]. Sydney: SESLHD; https://www.seslhd.health.nsw.gov.au/royal-hospital-for-women/australasian-neonatal-medicines-formulary-anmf

The Sanford Guide to Antimicrobial Therapy. Dallas Texas: Antimicrobial Therapy Inc.; 2022

Beta-lactam Allergy

Clinical history is vital in determining a beta-lactam allergy. It is important to ascertain the timing of the reaction, as allergies may wane and patients with childhood allergies will often tolerate the drug as an adult. It is also important to ascertain the type of drug reaction the patient experienced, immediate versus delayed hypersensitivity, side effect versus true allergy. Something to consider is that childhood rashes are commonly caused by viruses, or drug-virus interactions.

History	Recommendation	Comments
Penicillin allergy Allergy to phenoxymethylpenicillin, benzylpenicillin, benzathine penicillin, amoxicillin, amoxicillin/ clavulanic acid, ampicillin, cloxacillin.	Penicillins: Avoid Cephalosporins: Cross reactivity 1-2% If mild allergy (e.g. rash, urticaria): Safe to give with some exceptions (see comments). If severe allergy (e.g. anaphylaxis, Stevens-Johnson, Toxic epidermal necrolysis): Avoid (see comments). Meropenem: Cross reactivity <1% If mild allergy (e.g. rash, urticaria): Safe to give. If severe allergy: Consider (see comments).	Do not give cefaclor or cephalexin to patients with allergies to ampicillin or amoxicillin, as these antibiotics share a side chain and have high rates of allergy cross-reactivity. In patients with immediate severe penicillin hypersensitivity (e.g. anaphylaxis) cephalosporins and meropenem can be considered in critical situations (e.g. sepsis, meningitis), after a risk-benefit analysis.

History	Recommendation	Comments
Cephalosporin allergy Allergy to cefazolin, ceftriaxone, cefuroxime, cefixime.	Penicillins: Cross reactivity 1-2% If mild allergy (e.g. rash, urticaria): Safe to give with some exceptions (see comments in Penicillin allergy). If severe allergy (e.g. anaphylaxis, Stevens-Johnson, Toxic epidermal necrolysis): Avoid (see comments in Penicillin allergy). Cephalosporins: Avoid with some exceptions (see comments). Meropenem: Cross reactivity <1% If mild allergy (e.g. rash, urticaria): Safe to give. If severe allergy: Consider (see comments in Penicillin allergy).	Cefazolin does not share side chains with any other available penicillins or cephalosporins, and so the risk of allergy cross-reactivity with this antibiotic is low. Cefazolin may be considered in patients with allergies to other cephalosporin or penicillins, and other cephalosporins or penicillins may be considered in patients who are allergic to cefazolin, after a risk-benefit analysis

Childhood Immunization Schedule

Vaccine	Age of Administration
BCG, HepB, OPV 0	At birth or as soon as possible after birth. OPV 0 should only be given within 2 weeks of birth. BCG may be given until 12 months.
OPV 1, DTP-HepB-Hib 1, Rotavirus 1	6 weeks
OPV 2, DTP-HepB-Hib 2, Rotavirus 2	10 weeks (or 4 weeks after OPV 1, DTP-HepB-Hib 1, Rotavirus 1)
OPV 3, DTP-HepB-Hib 3, IPV 3, Rotavirus 3	14 weeks (or 4 weeks after OPV 2, DTP-HepB-Hib 2, Rotavirus 2)
MR 1	9 months
OPV 4, DTP-HepB-Hib, MR2	18 months
DT	6 years or school entry