Needle Stick Injury: HIV Prophylaxis

Risk of seroconversion

• Deep injury (odds ratio [OR] 15)
• A device visibly contaminated with the patient's blood (OR 6.2)
• Needle placement in a vein or artery (OR 4.3)
• Terminal illness in the source patient (OR 5.6)
• The majority of cases were injured by a hollow bore as opposed to a solid needle

Initial actions following exposure

• immediate cleansing of the exposed site.
• Small wounds and punctures may be cleansed with an antiseptic such as an alcohol-based hand hygiene agent, since alcohol is virucidal to HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV).
• Other antiseptics such as iodophors, chloroxylenol (PCMX) and chlorhexidine (CHG) also inactivate HIV

Testing for HIV 

• Baseline and follow-up serologic testing for HIV should be performed in all HCP exposed to HIV to see if seroconversion occurred.
• The majority of individuals who seroconvert will do so within the first three months.
• Testing should be performed even among those who receive PEP

Post Exposure Prophylaxis

• offer post-exposure prophylaxis (PEP) using a three-drug regimen to healthcare personnel (HCP) with a percutaneous, mucous membrane, or nonintact skin exposure to body fluids of concern (eg, blood or blood tinged fluids) if the source patient is, or is suspected to be, HIV-infected
• PEP should be discontinued if testing shows that the source patient is HIV-negative, unless there is concern that the source is acutely infected with HIV
• If the HIV status of the source patient is unknown, offer PEP while awaiting HIV testing if the source has risk factors for HIV infection (eg, injection drug users, men who have sex with men) or symptoms suggesting HIV infection.
• If the source patient is unknown, do not administer PEP unless the exposure occurred in a setting where exposure to HIV is likely (eg, a needlestick from a sharps container in an HIV clinic

Timing 

• PEP should be initiated as soon as possible.
• The goal is to start within one to two hours (or earlier) after exposure, often using a "starter pack" with appropriate drugs that are immediately available.
•  It is likely that a delay in initiating PEP can reduce efficacy
• For most HCP, we do not initiate PEP if more than 72 hours have elapsed after the initial exposure; PEP is likely to be less effective when administered after that period of time.
•  However, we offer three-drug PEP after a longer interval to patients with a very high-risk exposure (eg, sharps injuries from a needle that was in an artery or vein of an HIV-infected source patient).
• For such HCP, The United States Public Health Services suggests that PEP can be offered up to one week after the exposure

Selection of antiretroviral therapy

• Tenofovir-emtricitabine (300/200 mg once daily) plus raltegravir (400 mg twice daily)
• Tenofovir-emtricitabine (300/200 mg once daily) plus dolutegravir (50 mg once daily)

PEP during pregnancy

•  For pregnant HCP who have an occupational exposure to HIV and choose to initiate post-exposure prophylaxis (PEP), we typically use the same regimen as noted above, namely tenofovir-emtricitabine (available as Truvada) plus raltegravir

Duration of therapy 

• The recommended duration of PEP is four weeks because a course of zidovudine for this duration appeared protective in some studies; however, the optimal duration of PEP is unknown
• PEP should be discontinued if testing shows that the source patient is HIV-negative

Reference:

www.uptodate.com

Lactulose in Diabetes

Lactulose

• consists of the monosaccharides fructose and galactose
• In the colon, lactulose is broken down primarily to lactic acid, and also to small amounts of formic and acetic acids, by the action of via evolved-beta galactosidase from colonic bacteria, which results in an increase in osmotic pressure and slight acidification of the colonic contents.
• This in turn causes an increase in stool water content and softens the stool.
• In treating heptic diseases (hepatic encephalopathy) it is thought that lactulose draws out ammonia from the body in the same way that it draws out water into the colon.

Affect on Sugar level

• The interaction of lactulose and diabetes is categorised as ‘moderate’
• Product information states that there is a possibility of affected glycaemic control
• Lactulose may contain more than 5 g lactose/galactose/epilactose depending upon the dose taken. This should be taken into account in patients with diabetes mellitus. [15 ml of Lactulose contain 42.7 KJ (10.2 kcals) = 0.21 BU]

Glycaemic Index

• In terms of glycaemic Index, comparatively lactose (45) and galactose (25) has lower index compared to glucose (100).
• However do keep in mind that GI value represents the type of carbohydrate in a food but says nothing about the amount of carbohydrate typically eaten. Thus, a higher consumption of lower index food is still able to increase the sugar level

Studies: Galactose

• Following galactose ingestion, there was a modest transient increase in peripheral glucose and insulin concentrations. This was associated with a modest increase in the glucose Ra (rate of glucose appearance)
• conversion of galactose to glucose in the liver may have been greater than suggested by the increase in glucose appearance in the circulation due to substitution for other gluconeogenic substrates
• Oral galactose is a relatively potent insulin secretagogue, and the insulin response is also additive to that following glucose ingestion

Studies: Lactose

• decrease in the glucagon area response observed with 25 g galactose + 25 g glucose or 50 g lactose was less than that with ingestion of 25 g glucose alone. The latter suggests inhibition of the glucagon response to glucose by the added galactose

Studies : Lactulose

• In a study to test the effects of a preparation containing fibre and lactulose in the form of biscuits on glucose and insulin levels in obesity, they found a contradicting trend that glucose and insulin in response to breakfast and to lunch were blunted by dietary fibre and lactulose, without any trend towards post-meal hypoglycaemia
• However, there is also a single case report that reported a case of a patient with diet-controlled diabetes and cirrhosis who experienced a marked deterioration in glycemic control, requiring insulin use, when he began using a different brand of lactulose syrup. The hyperglycemia resolved and insulin was discontinued after use of the original brand of lactulose syrup was resumed

Recommendations

• Most references suggest of being cautious to the addition of lactulose. However this is not a contraindication
• While may affect the sugar level, most likely it will not affect levels significantly to the extent of impacting diabetes control
• Based on guidelines and data from published literature, food and dietary change with exercise and lifestyle change should be the first step in management. For patients recalcitrant to these changes, laxatives should be the next step of treatment. Treatment should begin with bulking agents such as psyllium, bran or methylcellulose followed by osmotic laxatives if response is poor

References:

1. https://www.drugs.com/disease-interactions/lactulose.html
2. https://www.ncbi.nlm.nih.gov/pubmed/11172481
3. http://www.metabolismjournal.com/article/0026-0495(93)90151-D/pdf
4. https://www.medicines.org.uk/emc/medicine/25597
5. https://beta.nhs.uk/medicines/lactulose/
6. https://www.ncbi.nlm.nih.gov/pubmed/9145450
7. https://www.ncbi.nlm.nih.gov/pubmed/7716610
8. https://www.ncbi.nlm.nih.gov/pubmed/27987136
   

Comparison of oral antifungals

Availability in Hospital Keningau

• Cap Fluconazole 50mg & 200mg
• Tab Griseofulvin 125mg
• Cap Itraconazole 100mg
• Tab Ketoconazole 200mg 
• Suspension Nystatin 100 000 units/ml

Comparison of Oral Antifungals

Antifungal	Indication (FUKKM)	Pharmacokinetics
Ketoconazole 200mg (B)	Pityriasis Versicolor Systemic Mycoses (other skin mycosis) Nail infection	Absorption can be increased by administration with a cola beverage (requires acidic condition) Half life elimination is biphasic (initial 2 hours and terminal 8 hours)
Fluconazole 50mg Fluconazole 100mg (A)	Oropharyngeal candidiasis, atrophic oral candidiasis Tinea Pedis, corporis, cruris, versicolor and dermal candidiasis Invasive candida & cryptocococcal infections (includes meningitis) Prevention of relapse cryptococcal meningitis in AIDS after completion of primary therapy Prevention of fungal infections in immunocompromised patients	Oral bioavailability > 90% The long serum half-life (approximately 24 hours) allows once-daily dosing Good penetration into CSF Absorption is not affected by the presence of food or gastric pH.
Itraconazole 100mg (A/KK)	Dermatomycosis including pityriasis versicolor Oral candidiasis Palmar tinea manus and plantar tinea pedis Fingernail onychomycosis Toenail onychomycosis Vulvovaginal candidiasis	Capsule bioavailability of approximately 55% Relatively long half-life, approaching 25 to 50 hours thus allows OD dosing Absorption increased by concurrent ingestion of cola or cranberry juice
Voriconazole 200mg Voriconazole 50mg (A*)	Treatment of immunocompromised patients with progressive, possibly life-threatening infections such as invasive aspergillosis, fluconazole-resistant serious invasive candidiasis, candidiasis of the oesophagus, serious fungal infections caused by Scedosporium species and Fusarium species Prevention of breakthrough fungal infections in febrile high risk neutropenic patients	Oral biovailability >90% in adult and may vary with <12 year old Ability to penetrate CSF
Syr. Nystatin 500 000 (B)	Prevention and treatment of candidiasis of the skin and mucous membranes Protection against candidas overgrowth during antimicrobial /corticosteroid therapy and as selective decontamination regimens	Poorly absorbed Excreted unchanged at feces  Should be swished about the mouth and retained in the mouth for as long as possible (several minutes) before swallowing.
Griseofulvin (B)	Dermatophyte infection of the skin, scalp, hair and nails, where topical therapy has failed or inappropriate	Absorption is almost complete (ultramicrosize) Half life elimination is 9-24 hours
Flucytosine 500mg (A*)	Only for the treatment of fungal meningitis	Ability to penetrate CSF Bioavailability 78%-89% (decreased in neonates

Spectrum of activity

Imidazole (Ketoconazole)

• Ketoconazole causes more gastrointestinal disturbances compared to other azoles.
• Has been largely replaced by other triazoles due to favourable pharmacokinetic and safety profile
• Should not be used as first-line treatment for any fungal infection.
• It should be used for the treatment of endemic mycoses (eg, histoplasmosis, blastomycosis) only when alternative antifungal therapies are not available or tolerated.
• Contraindicated in acute or chronic liver disease.

Triazole (Itraconazole, Fluconazole, Voriconazole)

• The drugs in this class offer activity against many fungal pathogens without the serious nephrotoxic effects observed with amphotericin B 
• Due to its inotropic effects, itraconazole’s labeling includes a black box warning in patients with heart failure, particularly in patients receiving a total daily oral dose of 400 mg

Pyrimidine (Flucytosine)

• Flucytosine has limited clinical indication and is used primarily in combination with Amphotericin B as combination therapy for cryptococcal meningitis and selected life threatening Candida syndromes                 

References

• Uptodate
• https://mycology.adelaide.edu.au/docs/antifungals.pdf 
• https://www.uspharmacist.com/article/the-fungus-among-us-an-antifungal-review 
• Lexicomp 
• FUKKM