Empirical Treatment for Infective Balanitis

ü  Balanitis is the inflammation of glans penis, while posthitis is inflammation of prepuce (foreskin). Since both areas are often affected, the term balanoposthitis is then used.

ü  Factors that can cause balanitis are listed in the table below:

Infectious	Dermatoses	Miscellaneous
Candida albicans	Lichen sclerosus (balanitis xerotica obliterans)	Trauma
Trichonomas vaginalis	Zoon’s balanitis	Irritant
Streptococci (Group A and B)	Psoriasis	Poor hygiene
Anaerobes	Circinate balanitis	Pre-malignant conditions: · Bowen’s disease · Bowenoid papulosis · Erythroplasia of Queyrat
Gardnerella vaginalis	Lichen planus
Staphylococcus aureus	Immuno-bullous disorders
Mycobacteria	Contact allergy
Entamoeba histolytica	Fixed drug eruption
Syphilis	Stevens-Johnson syndrome
Herpes simplex virus
Human papillomavirus

ü  Empirical treatment for balanitis:

	Candidal	Anaerobic	Aerobic
Clinical Presentations	§  Rash, with soreness and/or itch §  Blotchy erythema with small papules (may be eroded, or dry dull red areas with glazed appearance)	§  Foul smelling discharge, swelling and inflamed glands §  Preputial oedema, superficial erosions, inguinal adenitis	§  Non specific balanitis
First choice antibiotic	Clotrimazole 1% cream topically BD until symptoms settle	Metronidazole 400mg PO BD for 7 days	As per sensitivities
Second choice antibiotic	For severe symptoms: Fluconazole 150mg PO stat	Augmentin 375mg PO TDS for 7 days

References:
1. 2008 UK National Guideline on the Management of Balanoposthitis. http://www.bashh.org/documents/2062.pdf
2. NHS Grampian Medicines Management. Hospital empirical antibiotic therapy for adults. Infective balanitis. http://www.nhsgrampian.org/nhsgrampian/GJF_general_new.jsp?pContentID=5779&p_applic=CCC&pElementID=871&pMenuID=464&p_service=Content.show&

Pharmacological Management of Refractory Seizure

ü Defined as patients with epilepsy whose seizures do not successfully respond to two tolerated, appropriately chosen and administered antiepileptic drug (AED) therapy, either as monotherapy or in combination.

ü Review whether:

- Diagnosis of epilepsy is correct

- Patient is compliant to their AED.

- Past AED trials are appropriate to individual’s seizure-type:

Seizure type	AED
Broad spectrum: all seizure types (generalized from onset and focal onset seizures)	Clobazam, felbamate, lamotrigine, levetiracetam, rufinamide, topiramate, valproate, zonisamide
Narrow spectrum: focal with or without alteration in consciousness or awareness and focal evolving to bilateral convulsive seizure	Carbamazepine, eslicarbazepine, ezogabine, gabapentin, lacosamide, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, tiagabine, vigabatrin
Absence seizure (a type of generalized seizure)	Ethosuximide

ü Firstly, optimize AED monotherapy based on evidence for seizure type or syndrome-specific efficacy.

ü If failed, prescribe an alternative AED and optimize dosage.

ü If two monotherapy failed, consider AED combination. Choice of combination should be guided by side effect profile and drug interactions

ü Choosing AEDs with different mechanism of action may enhance effectiveness, such as lamotrigine with sodium valproate:

References:

1. UpToDate. Evaluation and management of drug-resistant epilepsy. http://www.uptodate.com/contents/evaluation-and-management-of-drug-resistant-epilepsy#H16

2. SIGN. Diagnosis and Management of Epilepsy in Adults. http://www.sign.ac.uk/guidelines/fulltext/70/section3.html

3. Mitchell JW, Seri S, Cavanna AE. Pharmacotherapeutic and Non-Pharmacological Options for Refractory and Difficult-to-Treat Seizures. J Cent Nerv Syst Dis. 2012; 4: 105-115. 

Peritoneal Dialysis-Related Infection

Exit-site and tunnel infections

ü Defined as presence of purulent drainage with or without erythema of skin at catheter-epidermal interface.

ü Oral antibiotic therapy is generally recommended, except MRSA

ü Pseudomonas aeruginosa exit-site infections required two antibiotics: Oral fluoroquinolones and either IP aminoglycoside, ceftazidime, cefepime, piperacillin, imipenem cilastatin or meropenem.

ü Continue antibiotic therapy until exit site appears entirely normal, minimum length of treatment time is 2 weeks. Infections caused by P. aeruginosa may need 3 weeks, and earlier catheter removal should be considered.

Peritonitis

ü  Peritoneal dialysis patients presenting with cloudy effluent should be presumed to have peritonitis. This is confirmed by obtaining effluent cell count, differential, and culture.

ü Important to initiate empiric antibiotic therapy for PD-associated peritonitis as soon as possible to prevent serious consequences such as relapse, catheter removal, permanent transfer to hemodialysis,   and death.

ü Bacteremia is uncommon in peritoneal dialysis-associated peritonitis. Infection is usually localized in the peritoneum and few cell layers lining the peritoneal cavity and intra-abominal viscera.

ü Empiric antibiotics must cover both gram-positive and gram-negative organisms.

ü IP administration is superior to IV dosing for treating peritonitis; intermittent and continuous dosing of antibiotics are equally efficacious.

Indications for catheter removal:

• Relapsing peritonitis
• Refractory peritonitis
• Refractory catheter infections
• Fungal or mycobacterial peritonitis
• Peritonitis occurring in association with intra-abdominal pathology

References:

1. ISPD Guidelines / Recommendations. Peritoneal Dialysis-Related Infections Recommendatins: 2010 Update.

2. UpToDate. Microbiology and therapy of peritonitis in continuous peritoneal dialysis. http://www.uptodate.com

Breastfeeding recommendations for Daflon

Manufacturers recommendations:

• In the absence of data concerning the diffusion into breast milk,breastfeeding is not recommended during treatment

Factors to Consider during Dosing: 

• Expression into breastmilk (in rats):
• passage into breast milk was assessed as 1% of the dose administered to the mother
• Volume of distribution is 60L. 
• the higher volume distribution means the lesser tendency to stay in the blood and will distribute to other body fluid
• Half life: 26-43hours. 
• Thus it takes about 1-2 days to achieve 50% of drug level in blood. 
• Some recommendations is to wait about 7-10 days (6-7 half life) before starting to breastfeed.
• Monitoring parameter: 
• based on pregnancy information in rat/mice, no teratogenicity was seen. 
• Thus no information of factors to monitor

References:

1. daflon 500mg.  http://www.mims.com/Malaysia/drug/info/Daflon%20500%20mg/?type=full
2. Safety and security of Daflon 500 mg in venous insufficiency and in hemorrhoidal disease. http://www.ncbi.nlm.nih.gov/pubmed/8203791
3. Diosvein. http://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-rpt0325-04-Tab-C-vol257.pdf
4. Daflon 500. http://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-rpt0358-02-Submission-for-Diosmin-vol280.pdf

Comparison between Midazolam and Propofol for Sedation

	Midazolam	Propofol
USE	·         sedation, amnesia, ·         anxiolysis; ·         no analgesia ·         useful for many types of procedures; can combine with an analgesic	·         sedation ·         mild antiemetic effect ·         use for intubation, brief procedures (may redose for longer procedures)
ADVANTAGES	·         short duration ·         [onset: 5-15 min (20 with PR)] ·         minimal cardiovascular effects	·         very rapid return to baseline after discontinuing use
DISADVANTAGES	·         respiratory depression ·         (rate-dependent; give IV slowly), ·         duration may be prolonged with oral doses > 0.5 mg/kg	·         limited experience in children, use with caution ·         cost
	·         Both agents are comparable in terms of EFFICACY and SIDE EFFECT

REFERENCES:

1. Conscious sedation in interventional radiology: A comparison of Propofol versus Midazolam http://www.sedationconsulting.com/about/principals/143-propofol-vs-midazolam-article
2. UNIVERSITY OF VIRGINIA CHILDREN'S HOSPITAL PEDIATRIC SEDATION FOR DIAGNOSTIC AND THERAPEUTIC PROCEDURES

Use of Topical Heparin

EVIDENCES

• A total of 1055 patients participated in a total of 20 studies that compared topical heparin formulations in the treatment of superficial thrombophlebitis or venous insufficiency.
• Heparin gel 1000 IU/g (Lioton) 1000 gel, Menaven) 1000 gel) was more effective than placebo in reducing the signs and symptoms of superficial thrombophlebitis.
• Liposomal heparin gel 2400 IU/g (LipoHep Forte) was as effective as subcutaneous low-molecular-weight heparin at relieving local symptoms of superficial venous thrombosis.
• all preparations appeared effective but heparin gel 1000 IU/g was superior to a heparinoid mucopolysaccharide cream (Hirudoid) in patients with vascular disorders in terms of resolving spontaneous pain, induced pain, oedema and heaviness in the limb
• All treatments were generally well tolerated, with a relatively low incidence of local skin events.
• current comparative study demonstrates that heparin significantly decreases the requirement of analgesics and the time required to prepare a burn wound for grafting. Besides as compared to silver sulfadiazine dressings, heparin appears to be cost-effective

CONCLUSION

• May be useful for relieving the signs and symptoms of vascular disorders while improving microcirculation.
• There is some evidence to suggest that heparin gel 1000 IU/g may be more effective than other topical preparations in treating these conditions, possibly because of the relatively high heparin levels in this formulation. This remains to be tested in well controlled, adequately powered clinical trials.

FURTHER INFORMATION:

• Three main local actions of heparin on the skin can be defined:
• anticoagulant action
• microcirculatory-modulatory action determining important control of the microcirculation in case of excessive vasoconstriction or vasodilatation
• 'facilitatory action' on skin permeability allowing other drugs to diffuse better and faster into the skin (producing a therapeutic effect)

REFERENCES

1. Topically applied heparins for the treatment of vascular disorders : a comprehensive review http://www.ncbi.nlm.nih.gov/pubmed/18783299
2. Topical heparin versus conventional treatment in acute burns: A comparative study http://www.ijburns.com/article.asp?issn=0971-653X;year=2014;volume=22;issue=1;spage=43;epage=50;aulast=Masoud

Safety of Azithromycin in patients with Cardiovascular Risks

• Not contraindicated/ but as Warning and Precaution
• azithromycin (Zithromax or Zmax) can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm.
• a clinical QT study which showed that azithromycin can prolong the QTc interval
• Patients at particular risk for developing this condition include

- existing QT interval prolongation
- low blood levels of potassium or magnesium
- a slower than normal heart rate
- use of certain drugs used to treat abnormal heart rhythms, or arrhythmias
- Elderly patients and those at high risk for cardiovascular disease were also considered to be more susceptible to the adverse effects of azithromycin

• Alternative drugs in the macrolide class, or non-macrolides such as the fluoroquinolones, also have the potential for QT prolongation or other significant side effects that should be considered when choosing an antibacterial drug.
• The study reported an increase in cardiovascular deaths, and in the risk of death from any cause, in persons treated with a 5-day course of azithromycin (Zithromax) compared to persons treated with amoxicillin, ciprofloxacin, or no drug. The risks of cardiovascular death associated with levofloxacin treatment were similar to those associated with azithromycin treatment.

Modifiable and Non-Modifiable Risk Factors for QT-Prolongation and Torsades de Pointes

 

References

1. Cardiac Risks With Antibiotics Azithromycin, Levofloxacin Supported by VA Data http://www.medscape.com/viewarticle/821697
2. FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms http://www.fda.gov/Drugs/DrugSafety/ucm341822.htm
3. Zithromax. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050710s039,050711s036,050784s023lbl.pdf

Dose of cephalexin for Urinary tract infection in prenancy

Causative agent: 
Most common: Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae
Less common: Staphylococcus saprophyticus, enterococci,Gardnerella vaginalis and Ureaplasma ureolyticum

Treatment:

Duration:
A 7-10-days course of antibiotic treatment is usually sufficient to eradicate the infecting organisms. 


References:
1. American Family Physician, 2000.
http://www.aafp.org/afp/2000/0201/p713.html

Use of Octreotide for healing of pancreaticoenteric anastomosis

RATIONALE:

• by decreasing the volume of pancreatic secretion, the pancreatic fistula rate would be decreased because of which the pancreaticoenteric anastomosis would heal better.
• Treatment with octreotide is proposed to decrease nutrient and electrolyte losses and promote fistula closure. Benefits of these actions would include decreased hospital stays, complication rates, and decreased overall cost of treatment

EVIDENCES

• Five RCTs from Europe and 1 RCT from Asia showed the benefit of perioperative use of somatostatin analogues to decrease the postoperative complication rate.
• On the other hand, 2 recent RCTs from Europe and 3 RCTs from USA tates failed to show benefit
• 10 studies and showed that somatostatin and its analogues reduced rate of biochemical fistula but not the incidence of clinical anastomotic disruption
• In another report involving seven studies, the perioperative octreotide administration was associated with significant reduction of pancreatic fistula rate after pancreatic surgery
• However the risk reduction was not associated with a significant difference in postoperative mortality.

RECOMMENDATION

• prophylactic use of perioperative somatostatin and its analogues to prevent pancreas-related complications after pancreatic surgery remains controversial.
• It does not result in a reduction of mortality.
• However the efficacy of prophylactic octreotide is reported to be improved, by selective administration in the setting of high risk glands, including patients with either soft glands or small pancreatic duct, in those harbouring ampullary, duodenal cystic or islet lesions, or in case where intraoperative blood loss is excessive
• Prophylactic octreotide did not influence clinically relevant fistula rates among low-risk glands. Thus the usage may incur high treatment cost without any significant additional benefit
• In addition, surgeons experience has been shown to correlate with pancreatic anastomotic leakage rate and in some reported cases the prophylactic use of somatostatin

DOSING:

• SC 0.1mg (up to 0.25mg in some references) TDS for 7 days (5-8 days)
• If clinical significant reduction in fistula output is  not evident within 5-8 days, octreotide therapy should be discontinued

REFERENCES:

1. Pancreatic Fistula after Pancreatectomy: Definitions, Risk Factors, Preventive Measures, and Management Review http://www.hindawi.com/journals/ijso/2012/602478/

2. Use of Octreotide for the prevention of pancreatic fistula after elective pancreatic surgery: a systemic review and meta analysis

3. OCTREOTIDE IN THE PREVENTION AND TREATMENT OF GASTROINTESTINAL AND PANCREATIC FISTULAS. Department of Surgical Education, Orlando Regional Medical Center (2005)

4. Therapeutic applications of octreotide in pediatric patients http://www.saudijgastro.com/text.asp?2012/18/2/87/93807

5. Does Prophylactic Octreotide Decrease the Rates of Pancreatic Fistula and Other Complications After Pancreaticoduodenectomy?http://www.cinj.org/sites/cinj/files/documents/ProphylacticOctreotide.pdf

Benefits of Tranexamic Acid mouthwash

• Tranexamic acid is an antifibrinolytic agent that inhibits the breakdown of fibrin clots. Its primary action is to block the binding of plasminogen and plasmin to fibrin therefore preventing fibrinolysis.
•  It has been used in anticoagulated dental patients as a local haemostatic agent in the form of a mouthwash

SUMMARY OF EVIDENCE

• When used alone with no local haemostatic dressing, tranexamic acid mouthwash reduces postoperative bleeding compared to placebo mouthwash.
• When used in combination with local haemostatic measures and suturing, tranexamic acid mouthwash provides little additional reduction in postoperative bleeding.

PRACTICAL ISSUES

• No tranexamic acid mouthwash available commercially
• The agents used in the study are either 4.8% tranexamic acid mouthwash or a tranexamic acid 500mg in a mouthwash
• No specific guides or recommendations on the administration. Based on practice and papers:
• 4.8% tranexamic acid mouthwash: rinse with 10ml for 2 minutes and expectorate, four times a day for 7 days
• Tranexamic acid 500mg in a mouthwash: used for 2 minutes, four times a day

MANUFACTURING

• The mouthwash is commonly made based on formula using IV tranexamic acid
• However, some practice do recommend the administration of oral 500mg Tranexamic acid dispersed into 10-15ml of water.

REFERENCES:

1. SURGICAL MANAGEMENT OF THE PRIMARY CARE DENTAL PATIENT ON WARFARIN. http://www.app.dundee.ac.uk/tuith/Static/info/warfarin.pdf
2. Preparing tranexamic acid 4.8% mouthwash. http://www.australianprescriber.com/magazine/26/4/75/7
3. Management of patients taking warfarin who require minor oral surgery. https://www.tg.org.au/etg_demo/phone/etg_dtg2_warfarin-and-minor-surgery.pdf