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Side effects of penicillin

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The side effects of penicillin are bodily responses to penicillin and closely related antibiotics that do not relate directly to its effect on bacteria. A side effect is an effect that is not intended with normal dosing.[1] Some of these reactions are visible and some occur in the body's organs or blood. Penicillins are a widely used group of medications that are effective for the treatment of a wide variety of bacterial infections in human adults and children as well as other species. Some side effects are predictable, of which some are common but not serious, some are uncommon and serious and others are rare.[2] The route of administration of penicillin can have an effect on the development of side effects. An example of this is irritation and inflammation that develops at a peripheral infusion site when penicillin is administered intravenously. In addition, penicillin is available in different forms. There are different penicillin medications (penicillin G benzathine, penicillin G potassium, Penicillin G sodium, penicillin G procaine, and penicillin V)[3] as well as a number of β-lactam antibiotics derived from penicillin (e.g. amoxicillin).

Side effects may only last for a short time and then go away. Side effects can be relieved in some cases with non pharmacological treatment.[4] Some side effects require treatment to correct potentially serious and sometimes fatal reactions to penicillin. Penicillin has not been found to cause birth defects.[5]

Allergies and cross sensitivities

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Many people have indicated that they have a side effect related to an allergic reaction to penicillin. It has been proposed that as many as 90% of those claiming to have an allergy to penicillin are able to take it and do not have a true allergy. Research has suggested that having penicillin allergy incorrectly noted in the medical records can have negative consequences.[6][7]

Identifying an allergy to penicillin requires a hypersensitivity skin test, which diagnoses IgE-mediated immune responses caused by penicillin. This test is typically performed by an allergist who uses a skin-prick and intradermal injection of penicilloyl-polylysine, a negative control (normal saline), and a positive control (histamine).[8]

A small proportion of people who are allergic to penicillins also have similar cross sensitivities to other antibiotics such as cephalosporins. If someone has developed side effects when taking penicillin, these side effects may develop with a new medication even though the person has not taken the new medication before. Those medications that may cause a cross sensitivity reaction are: carbapenems, ampicillin, cefazolin, cephalosporins and cloxacillin.[9][8][10]

Risk assessment and "de-labelling"

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Of patients with documented penicillin allergy, approximately 95% will return a negative penicillin skin-prick test[11] but patients carrying a penicillin allergy label are significantly more likely to experience worse outcomes.[12] As such, it is important for clinicians to verify the nature of reported penicillin allergy at admission and de-label when appropriate.

For this purpose, clinical risk assessment tools have been developed such as "PEN-FAST":

Patients scoring 4 or greater have a high (50%) probability of testing positive for penicillin allergy.[13]

Side effects in adults

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Common adverse drug reactions (≥ 1% of people) associated with use of the penicillins include diarrhea, hypersensitivity, nausea, rash, neurotoxicity, urticaria (hives), and superinfection (including candidiasis). Infrequent adverse effects (0.1–1% of people) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in people with epilepsy), and pseudomembranous colitis.[14][needs update]

Very common (>10% incidence)

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Common (1-10% incidence)

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Uncommon (<1%)

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Life threatening

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Rare (<0.1%)

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High doses

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When penicillin is used at high doses hypokalemia, metabolic acidosis, and hyperkalemia can occur.[17] Developing hypernatremia after administering high doses of penicillin can be a serious side effect.[10]

Side effects from other medications

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The side effects of penicillin can be altered by taking other medications at the same time. Taking oral contraceptives along with penicillin may lower the effects of the contraceptive. When probenecid is used concurrently with penicillin, kidney excretion of probenecid is decreased resulting in higher blood levels of penicillin in the circulation. In some instances, this would be an intended therapeutic effect. In other instances, this is an unintended side effect. Neomycin can lower the absorption of penicillin from the gastrointestinal tract resulting in lower than expected levels of penicillin in the circulation. This side effect may result in an ineffective therapeutic effect of penicillin. When methotrexate is administered with penicillin, toxicity may occur related to methotrexate.[10]

In animals

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Animals are often treated with antibiotics for infections they have developed. There are side effects of penicillin when it is used in animals. MRSA may develop in pets as a consequence of treatment.[18][19] Nutritional deficiencies can develop in pets as a side effect.[20] Destruction of the normal protective flora of beneficial bacteria can occur in dogs and horses.[21][22] Dogs may have side effects that include: joint pain, loss of appetite, vomiting, flatulence (intestinal gas), fungal infections and digestive problems.[23] Like humans, dogs can have a similar side effect related to developing a serious allergy. A serious and possibly fatal anaphylactic can occur. Side effects that are concurrent with anaphylaxis include: breathing problems and shock.[citation needed]

Cats and dogs have had adverse reactions to intravenous penicillin that include: hypothermia, pruritus, hypotension, tremors, seizures, blindness, vocalization, agitation, cardiac arrest and transient loss of vision.[24]

Other side effects

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Penicillin is known to become less effective as strains of bacteria become resistant.[25]

References

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  1. ^ "Definitions" (PDF). The World health organization. Retrieved May 20, 2017.
  2. ^ Vallerand 2017, pp. 3–4.
  3. ^ Karch 2017, p. 115.
  4. ^ a b c d "Penicillin (Oral Route, Injection Route, Intravenous Route, Intramuscular Route) Side Effects - Mayo Clinic". www.mayoclinic.org. Retrieved 18 May 2017.
  5. ^ "Penicillin use during pregnancy not linked to birth defects". 16 December 2009. Retrieved 19 May 2017.
  6. ^ "Are you sure you are allergic to penicillin?". NIHR Evidence. 2022-01-20. doi:10.3310/alert_48839. S2CID 246149945. Retrieved 2022-06-24.
  7. ^ Wanat, Marta; Anthierens, Sibyl; Butler, Christopher C.; Savic, Louise; Savic, Sinisa; Pavitt, Sue H.; Sandoe, Jonathan A. T.; Tonkin-Crine, Sarah (2021-06-11). "Management of penicillin allergy in primary care: a qualitative study with patients and primary care physicians". BMC Family Practice. 22 (1): 112. doi:10.1186/s12875-021-01465-1. ISSN 1471-2296. PMC 8194168. PMID 34116641.
  8. ^ a b Gonzalez-Estrada, A.; Radojicic, C. (2015). "Penicillin allergy: A practical guide for clinicians". Cleveland Clinic Journal of Medicine. 82 (5): 295–300. doi:10.3949/ccjm.82a.14111. ISSN 0891-1150. PMID 25973877. S2CID 6717270.
  9. ^ "Pharmaceutical Sciences CSU Parenteral Antibiotic Allergy cross-sensitivity chart" (PDF). Vancouver Acute Pharmaceutical Sciences, Vancouver Hospital & Health Sciences Centre. 2016. Archived from the original (PDF) on April 17, 2016. Retrieved May 19, 2017.
  10. ^ a b c d e f Vallerand 2017, pp. 989–994.
  11. ^ Sacco, K. A.; Bates, A.; Brigham, T. J.; Imam, J. S.; Burton, M. C. (September 2017). "Clinical outcomes following inpatient penicillin allergy testing: A systematic review and meta-analysis". Allergy. 72 (9): 1288–1296. doi:10.1111/all.13168. ISSN 1398-9995. PMID 28370003. S2CID 13757804.
  12. ^ Blumenthal, Kimberly G.; Ryan, Erin E.; Li, Yu; Lee, Hang; Kuhlen, James L.; Shenoy, Erica S. (2018-01-18). "The Impact of a Reported Penicillin Allergy on Surgical Site Infection Risk". Clinical Infectious Diseases. 66 (3): 329–336. doi:10.1093/cid/cix794. ISSN 1537-6591. PMC 5850334. PMID 29361015.
  13. ^ Trubiano, Jason A.; Vogrin, Sara; Chua, Kyra Y. L.; Bourke, Jack; Yun, James; Douglas, Abby; Stone, Cosby A.; Yu, Roger; Groenendijk, Lauren; Holmes, Natasha E.; Phillips, Elizabeth J. (May 2020). "Development and Validation of a Penicillin Allergy Clinical Decision Rule". JAMA Internal Medicine. 180 (5): 745–752. doi:10.1001/jamainternmed.2020.0403. ISSN 2168-6106. PMC 7076536. PMID 32176248.
  14. ^ Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 978-0-9757919-2-9. (subscription required)
  15. ^ Ohlsson, Arne; Shah, Vibhuti S; Ohlsson, Arne (2014). "Intrapartum antibiotics for known maternal Group B streptococcal colonization". Cochrane Database of Systematic Reviews. 2016 (6): CD007467. doi:10.1002/14651858.CD007467.pub4. PMID 24915629. S2CID 205189572.
  16. ^ Cooper, Chuck (9 January 2015). "Bioterrorism and Drug Preparedness - Safety of Long Term Therapy with Penicillin and Penicillin Derivatives". www.fda.gov. Center for Drug Evaluation. Retrieved 19 May 2017.
  17. ^ Potter 2013, p. 897.
  18. ^ Harrison, E. M.; Weinert, L. A.; Holden, M. T. G.; Welch, J. J.; Wilson, K.; Morgan, F. J. E.; Harris, S. R.; Loeffler, A.; Boag, A. K.; Peacock, S. J.; Paterson, G. K.; Waller, A. S.; Parkhill, J.; Holmes, M. A. (2014). "A Shared Population of Epidemic Methicillin-Resistant Staphylococcus aureus 15 Circulates in Humans and Companion Animals". mBio. 5 (3): e00985–13–e00985–13. doi:10.1128/mBio.00985-13. ISSN 2150-7511. PMC 4030480. PMID 24825010.
  19. ^ Briggs, Helen (22 May 2014). "MRSA: Hospital superbug 'shared with pets'". The British Broadcasting Company. Retrieved 20 May 2017 – via www.bbc.com.
  20. ^ "Three Things Every Dog Owner Should Know About Antibiotics - Dogs Naturally Magazine". 27 May 2013. Retrieved 19 May 2017.
  21. ^ "The Dangers of Antibiotic Misuse and Your Dog - Whole Dog Journal". www.whole-dog-journal.com. 29 January 2004. Retrieved 19 May 2017.
  22. ^ Costa, Marcio C; Stämpfli, Henry R; Arroyo, Luis G; Allen-Vercoe, Emma; Gomes, Roberta G; Weese, J (2015). "Changes in the equine fecal microbiota associated with the use of systemic antimicrobial drugs". BMC Veterinary Research. 11 (1): 19. doi:10.1186/s12917-015-0335-7. ISSN 1746-6148. PMC 4323147. PMID 25644524.
  23. ^ "What is the correct dosage of penicillin for dogs?". 4 August 2015. Retrieved 19 May 2017.
  24. ^ Kaplan, Megan I.; Lee, Justine A.; Hovda, Lynn R.; Brutlag, Ahna (2011). "Adverse effects associated with inadvertent intravenous penicillin G procaine-penicillin G benzathine administration in two dogs and a cat". Journal of the American Veterinary Medical Association. 238 (4): 507–510. doi:10.2460/javma.238.4.507. ISSN 0003-1488. PMID 21320022.
  25. ^ Li, Shunming; Huang, Jingya; Chen, Zhiyao; Guo, Dan; Yao, Zhenjiang; Ye, Xiaohua (2017). "Antibiotic Prevention for Maternal Group B Streptococcal Colonization on Neonatal GBS-Related Adverse Outcomes: A Meta-Analysis". Frontiers in Microbiology. 8: 374. doi:10.3389/fmicb.2017.00374. ISSN 1664-302X. PMC 5355432. PMID 28367139.

Bibliography

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  • Henry, Norma (2016). RN nursing care of children : review module. Stilwell, KS: Assessment Technologies Institute. ISBN 9781565335714.
  • Karch, Amy (2017). Focus on nursing pharmacology. Philadelphia: Wolters Kluwer. ISBN 9781496318213.
  • Potter, Patricia (2013). Fundamentals of nursing. St. Louis, Mo: Mosby Elsevier. ISBN 9780323079334.
  • Vallerand, April (2017). Davis's drug guide for nurses. Philadelphia: F.A. Davis Company. ISBN 9780803657052.
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