- Antibiotics are indicated to prolong latency and reduce the risk of
early onset neonatal group B streptococcal (GBS) infection, as well as
for treatment of overt intraamniotic infection, if present.
- The regimen
of prophylactic antibiotics is given for seven days to patients at
<34 weeks of gestation at the time of membrane rupture
Prophylaxis
- Infection may lead to spontaneous
preterm labor or may be the indication for medically-indicated preterm
delivery.
- The goal of antibiotic therapy is to reduce the frequency of
maternal and fetal infection and thereby delay the onset of preterm
labor (ie, prolong latency) and the need for preterm delivery
Rationale
- Ampicillin specifically targets group B streptococcus, many aerobic
gram-negative bacilli, and some anaerobes.
- Azithromycin specifically
targets Ureaplasmas, which can be important causes of chorioamnionitis in this setting.
- Azithromycin also provides coverage of Chlamydia trachomatis, which is an important cause of neonatal conjunctivitis and pneumonitis
References:
- NAG 2014
- www.uptodate.com
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964356/
- http://www.aafp.org/afp/2011/0501/p1106.html
- https://www.rcog.org.uk/en/guidelines-research-services/guidelines/preterm-prom-in-a-group-b-strep-positive-woman---query-bank/
Availability:
- Ipratropium Bromide 0.5mg & salbutamol 2.5mg
- Dosage (adults & > 12 years)
- 1 respule 3-4 times daily
- One unit dose (respule) provides prompt relief in most cases.
- In severe cases, if an attack has not been relieved by one respule, two respules may be required
Administration
- respules should be used undiluted.
Pharmacokinetic
- For inhaled ipratropium is minimal, maximal responses usually develop over 30 to 90 minutes, lasting for four to six hours.
- The elimination half-life of ipratropium is approximately 3 to 4 hours after inhalation.
For Salbutamol significant bronchodilation occurs within minutes of inhalation of a therapeutic dose, persisting for three to four hours.
- The elimination half-life of salbutamol is estimated to range from 4 to 6 hours.
Reference:
- Duolin Respule Product Information Leaflet
Availability
- Ipratropium Bromide 500mcg/2ml
Administration
- dose of nebuliser solution may need to be diluted ato obtain a final volume suitable
for the particular nebuliser being used (usually 2 – 4 ml)
- if dilution
is necessary use only sterile sodium chloride 0.9% solution
Dose
Adults (including the elderly) and children over 12 years of age:
- 250 - 500 micrograms 3 to 4 times daily.
- For treatment of acute bronchospasm, 500 micrograms.
- Repeated
doses can be administered until the patient is stable. The time
interval between the doses may be determined by the physician.
- advisable not to exceed the recommended daily dose during
acute or maintenance treatment.
- Daily doses exceeding 2 mg should only be given under medical
supervision.
Children 6 - 12 years of age:
- 250 micrograms up to a total daily dose of 1mg (4 vials).
- The time interval between doses may be determined by the physician.
Children 0 – 5 years of age (for treatment of acute asthma only):
- 125 – 250 micrograms up to a total daily dose of 1 mg (4 vials).
- should be administered no more frequently than 6 hourly in children under 5 years of age.
- For acute bronchospasm, repeated doses may be administered until the patient is stable
Maximal Dose
- Inhalation of 0.04mg of ipratropium from a metered dose aerosol causes
bronchodilation, the maximal effect is seen after 30 - 60 minutes, with a
duration of 4 hours.
- This is a dose related effect and use of a
nebuliser produces greater bronchodilation, a dose of 0.5mg producing
maximal bronchodilation
- The half-life of elimination of the drug and metabolites is 3.6 hours.
The half-life of the terminal elimination phase is about 1.6 hours
Overdose:
- Palpitation and increases in heart rate have been produced with
inhaled doses of 5 mg.
- Side effects have not been caused by single
inhaled doses of 2 mg in adults and 1 mg in children. Single oral doses
of 30 mg of ipratropium bromide caused anticholinergic side effects,
but these did not require treatment.
- Severe overdose is
characterized by atropine-like symptoms like tachycardia, tachypnea,
high fever and central effects like restlessness, confusion and
hallucinations
References:
- http://www.medicines.org.uk/emc/medicine/27927
- https://www.ncbi.nlm.nih.gov/pubmed/1837931
Effectiveness
- Cloxacillin, Dicloxacillin and Flucloxacillin are considered comparable and have similar dose recommendations
- Oxacillin and Nafcillin are comparable in effectiveness and indication, however differs in dosing regimen
- example for MSSA
- Cloxacillin or flucloxacillin or dicloxacillin 25mg/kg up to 1g q6h
- Nafcillin or oxacillin 50mg/kg up to 2g q4h
Side Effects
- Flucloxacillin is reported to have higher, though rare, incidence of severe hepatic adverse effects than dicloxacillin, but a lower incidence of renal adverse effect
Pharmacokinetic
- flucloxacillin had a significantly longer serum elimination half-life
- extent of binding of flucloxacillin to the protein of human serum was
similar to that of oxacillin and cloxacillin and less than that of
dicloxacillin
Reference:
- Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006
- www.antimicrobe.org
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820086/
- https://www.nps.org.au/australian-prescriber/articles/what-to-use-instead-of-flucloxacillin
Availability : Injection 1mg/ml (Pharmaniaga)
Indication & Dosages (FUKKM)
- Prophylaxis of anaemia associated with Vitamin B12 deficiency
- 250-1000 mcg IM everymonth
- Uncomplicated pernicious anaemia or Vitamin B12 malabsorption
- Initial 100 mcg daily for 5-10 days followed by 100-200 mcg monthly until complete remission is achieved.
- Maintenance: up to 1000 mcg monthly. CHILD 30-50 mcg daily for 2 or more
weeks (to a total dose of 1- 5mg). OR AS PRESCRIBED.
Alternative dosing (BMJ)
- Patients with megaloblastic anaemia and pancytopenia require hospital admission
- An acute regimen of 1000 micrograms cyanocobalamin parenterally is given
daily for between 1 and 2 week
- then 1000 micrograms parenterally
once a week for up to 1 month, until significant reticulocytosis is seen
in the marrow.
- Folic acid supplementation may help reverse the
haematological abnormalities
- Acute and maintenance treatment of patients with mild to moderate
symptoms of vitamin B12 deficiency (haematological: mild anaemia;
neurological: dysaesthesia/paraesthesias, polyneuropathy, depression) is
with once-daily oral cyanocobalamin or once-monthly parenteral
cyanocobalamin
- In patients treated with oral cyanocobalamin, a response should be seen
within 2 months.
- If serum vitamin B12 does not rise significantly after 2
months of daily oral cyanocobalamin, clinicians should switch to
intramuscular vitamin B12 or consider other causes
Comparison with Oral route
- Parenteral therapy using the IM or SC route is by far the most reliable and most familiar treatment for vitamin B12 deficiency
- oral vitamin B12 in the form of cyanocobalamin in high doses could be
absorbed even in patients with pernicious anaemia or significant
terminal ileum resection
- Oral cyanocobalamin has been shown in meta-analysis to be as effective,
if not more effective, in patients with vitamin B12 deficiency.
- Although absorption occurs at dosages <1000
micrograms/day, there appears to be variable absorption and less than
maximal clinical and laboratory response.
- Absorption can be maximised by administering on an empty stomach
References:
- MIMS Gateway
- http://bestpractice.bmj.com/best-practice/monograph/822/treatment/step-by-step.html
Rationale:
- Budesonide and beclometasone dipropionate are considered
equivalent on a microgram for microgram basis (1:1 dose ratio).
- However, the type of hydrofluoroalkane (HFA)-propelled
beclometasone dipropionate (pMDI) (Qvar, IVAX) (available in Hospital Keningau)
delivers beclometasone dipropionate in extra fine particles so that more is
deposited in the lungs, leading to a 2:1 dose ratio with the CFC
budesonide/beclometasone dipropionate devices
- Half the dose of fluticasone propionate, mometasone furoate
or ciclesonide in micrograms is equivalent to a given dose of budesonide/beclometasone
dipropionate (2:1 dose ratio).
References:
- GINA 2017
- Drug Information Leaflet
- https://www.nice.org.uk/guidance/ta138/chapter/3-the-technologies
- http://www.bpac.org.nz/2017/ics.aspx
Pharmacokinetic
- time dependent activity
- tend to have higher volume of distribution and clearance, which may cause lower meropenam levels
- however, meropenem pharmacokinetics are similar between obese and non-obese
patients, so same dosages provide comparable pharmacodynamic exposures
for susceptible organisms between obese and non-obese patients
Effectiveness
- routine dose escalation not recommended as standard dosing regimen able to achieve adequate PD exposure for susceptible pathogen (MIC <2mg/ml)
- only the dosing 2g TDS and 1g QID was able to achieve MIC > 4mg/ml
- prolonging the infusion time to 3h enhanced the dosage regimen
Alternative Dosings
- similar clinical outcomes seen between traditional (1g TDS) and alternative
meropenem dosing (500mg QID) strategies in previous studies may extend to obese
patients
Conclusion
- dose escalation not recommended as standard dosing regimen able to achieve adequate PD exposure
- however doses can be increased if higher MIC is required, exm multi resistant p.aeruginosa.
References:
- http://formularyjournal.modernmedicine.com/formulary-journal/content/tags/antibiotics/underdosing-obesity-epidemic-focus-antibiotics
- Drug Dosing in Obesity: Volume I: Antimicrobials.
- https://idsa.confex.com/idsa/2015/webprogram/Paper51176.html
- http://docs.lib.purdue.edu/dissertations/AAI3719044/
- http://pusware.com/testpus/drug_Obesity_dosing.html
- UKCPA: Drug Dosing in Extremes of Body Weight in critically ill patients. 1st Edition (v1.0)September 2013
