Side effects of penicillin

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.{{Cite journal |date=2022-01-20 |title=Are you sure you are allergic to penicillin? |url=https://evidence.nihr.ac.uk/alert/are-you-sure-you-are-allergic-to-penicillin/ |access-date=2022-06-24 |website=NIHR Evidence |doi=10.3310/alert_48839 |s2cid=246149945 |language=en-GB}}{{Cite journal |last1=Wanat |first1=Marta |last2=Anthierens |first2=Sibyl |last3=Butler |first3=Christopher C. |last4=Savic |first4=Louise |last5=Savic |first5=Sinisa |last6=Pavitt |first6=Sue H. |last7=Sandoe |first7=Jonathan A. T. |last8=Tonkin-Crine |first8=Sarah |date=2021-06-11 |title=Management of penicillin allergy in primary care: a qualitative study with patients and primary care physicians |journal=BMC Family Practice |volume=22 |issue=1 |pages=112 |doi=10.1186/s12875-021-01465-1 |issn=1471-2296 |pmc=8194168 |pmid=34116641 |doi-access=free }}

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).{{cite journal|last1=Gonzalez-Estrada|first1=A.|last2=Radojicic|first2=C.|title=Penicillin allergy: A practical guide for clinicians|journal=Cleveland Clinic Journal of Medicine|volume=82|issue=5|year=2015|pages=295–300|issn=0891-1150|doi=10.3949/ccjm.82a.14111|pmid=25973877|s2cid=6717270|doi-access=free}}

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.{{cite web |publisher =Vancouver Acute Pharmaceutical Sciences, Vancouver Hospital & Health Sciences Centre |date =2016 |access-date =May 19, 2017 |url =http://www.vhpharmsci.com/vhformulary/Tools/ANTIBIOTIC%20CROSS-SENSITIVITY%20CHART.pdf |title =Pharmaceutical Sciences CSU Parenteral Antibiotic Allergy cross-sensitivity chart |archive-date =April 17, 2016 |archive-url =https://web.archive.org/web/20160417213010/http://www.vhpharmsci.com/VHFormulary/Tools/ANTIBIOTIC%20CROSS-SENSITIVITY%20CHART.pdf |url-status =dead }}{{sfn|Vallerand|2017|pages=989–994}}

Of patients with documented penicillin allergy, approximately 95% will return a negative penicillin skin-prick test{{Cite journal |last1=Sacco |first1=K. A. |last2=Bates |first2=A. |last3=Brigham |first3=T. J. |last4=Imam |first4=J. S. |last5=Burton |first5=M. C. |date=September 2017 |title=Clinical outcomes following inpatient penicillin allergy testing: A systematic review and meta-analysis |journal=Allergy |volume=72 |issue=9 |pages=1288–1296 |doi=10.1111/all.13168 |issn=1398-9995 |pmid=28370003|s2cid=13757804 |doi-access=free }} but patients carrying a penicillin allergy label are significantly more likely to experience worse outcomes.{{Cite journal |last1=Blumenthal |first1=Kimberly G. |last2=Ryan |first2=Erin E. |last3=Li |first3=Yu |last4=Lee |first4=Hang |last5=Kuhlen |first5=James L. |last6=Shenoy |first6=Erica S. |date=2018-01-18 |title=The Impact of a Reported Penicillin Allergy on Surgical Site Infection Risk |journal=Clinical Infectious Diseases|volume=66 |issue=3 |pages=329–336 |doi=10.1093/cid/cix794 |issn=1537-6591 |pmc=5850334 |pmid=29361015}} 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":

• PENicillin allergy reported (start assessment)
• Five years ago or less (2 points)
• Anaphylaxis occurred (2 points)
• Severe cutaneous adverse reaction such as SJS occurred (2 points)
• Treatment was required (1 point)

Patients scoring 4 or greater have a high (50%) probability of testing positive for penicillin allergy.{{Cite journal |last1=Trubiano |first1=Jason A. |last2=Vogrin |first2=Sara |last3=Chua |first3=Kyra Y. L. |last4=Bourke |first4=Jack |last5=Yun |first5=James |last6=Douglas |first6=Abby |last7=Stone |first7=Cosby A. |last8=Yu |first8=Roger |last9=Groenendijk |first9=Lauren |last10=Holmes |first10=Natasha E. |last11=Phillips |first11=Elizabeth J. |date=May 2020 |title=Development and Validation of a Penicillin Allergy Clinical Decision Rule |journal=JAMA Internal Medicine |volume=180 |issue=5 |pages=745–752 |doi=10.1001/jamainternmed.2020.0403 |issn=2168-6106 |pmc=7076536 |pmid=32176248}}

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.{{cite book | editor=Rossi S | title=Australian Medicines Handbook | year=2006 | location=Adelaide | publisher=Australian Medicines Handbook | isbn=978-0-9757919-2-9| title-link=Australian Medicines Handbook }} {{subscription required}}{{update inline|date=August 2023}}

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• diarrhea
• epigastric distress
• nausea
• vomiting
• pseudomembranous colitis
• interstitial nephritis
• rash
• urticaria (hives)
• eosinophilia
• leukopenia (decrease in white blood cells)
• allergic reactions
• superinfection{{sfn|Vallerand|2017|pages=989–994}}

{{div col end}}

{{div col}}

• yeast infection
• lack of therapeutic effect{{cite journal|last1=Ohlsson|first1=Arne|last2=Shah|first2=Vibhuti S|last3=Ohlsson|first3=Arne|title=Intrapartum antibiotics for known maternal Group B streptococcal colonization|journal=Cochrane Database of Systematic Reviews|issue=6|pages=CD007467|year=2014|volume=2016 |doi=10.1002/14651858.CD007467.pub4|pmid=24915629|s2cid=205189572 }}
• vaginal itching
• vaginal discharge
• white patches in the mouth and tongue

{{div col end}}

{{div col|colwidth=22em}}

• wheezing{{sfn|Vallerand|2017|pages=989–994}}
• fever
• joint pain
• lightheadedness
• fainting
• facial edema (puffiness of the face)
• red, scaly skin
• shortness of breath
• skin rash, hives
• irregular breathing{{cite web|url=http://www.mayoclinic.org/drugs-supplements/penicillin-oral-route-injection-route-intravenous-route-intramuscular-route/side-effects/drg-20062334|title=Penicillin (Oral Route, Injection Route, Intravenous Route, Intramuscular Route) Side Effects - Mayo Clinic|website=www.mayoclinic.org|access-date=18 May 2017}}

{{div col end}}

• anaphylaxis
• serum sickness
• seizures
• laryngeal edema{{sfn|Vallerand|2017|pages=989–994}}

{{div col|colwidth=18em}}

• tooth discoloration
• erythema multiforme
• vertigo
• decreased platelet count
• tinnitus
• convulsions
• hypertonia
• cardiac arrest
• cyanosis
• palpitations
• chest pain
• macular rash{{cite web|url=https://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm072755.htm|title=Bioterrorism and Drug Preparedness - Safety of Long Term Therapy with Penicillin and Penicillin Derivatives|publisher=Center for Drug Evaluation |first =Chuck |last= Cooper|date = 9 January 2015|website=www.fda.gov|access-date=19 May 2017}}
• yellow eyes or skin
• stomach or abdominal cramps
• severe abdominal pain
• bloody diarrhea
• depression
• decreased urine excretion
• sore throat
• bleeding or bruising
• agitation
• combativeness
• anxiety
• confusion
• hallucinations

{{div col end}}

When penicillin is used at high doses hypokalemia, metabolic acidosis, and hyperkalemia can occur.{{sfn|Potter|2013|page=897}} Developing hypernatremia after administering high doses of penicillin can be a serious side effect.{{sfn|Vallerand|2017|pages=989–994}}

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.{{sfn|Vallerand|2017|pages=989–994}}

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.{{cite journal|last1=Harrison|first1=E. M.|last2=Weinert|first2=L. A.|last3=Holden|first3=M. T. G.|last4=Welch|first4=J. J.|last5=Wilson|first5=K.|last6=Morgan|first6=F. J. E.|last7=Harris|first7=S. R.|last8=Loeffler|first8=A.|last9=Boag|first9=A. K.|last10=Peacock|first10=S. J.|last11=Paterson|first11=G. K.|last12=Waller|first12=A. S.|last13=Parkhill|first13=J.|last14=Holmes|first14=M. A.|title=A Shared Population of Epidemic Methicillin-Resistant Staphylococcus aureus 15 Circulates in Humans and Companion Animals|journal=mBio|volume=5|issue=3|year=2014|pages=e00985–13–e00985–13|issn=2150-7511|doi=10.1128/mBio.00985-13|pmid=24825010|pmc=4030480}}{{cite web|url=https://www.bbc.com/news/health-27500826|title=MRSA: Hospital superbug 'shared with pets'|first=Helen|last=Briggs|date=22 May 2014|publisher= The British Broadcasting Company|access-date=20 May 2017|via=www.bbc.com}} Nutritional deficiencies can develop in pets as a side effect.{{cite web|url=http://www.dogsnaturallymagazine.com/three-things-every-dog-owner-should-know-about-antibiotics/|title=Three Things Every Dog Owner Should Know About Antibiotics - Dogs Naturally Magazine|date=27 May 2013|access-date=19 May 2017}} Destruction of the normal protective flora of beneficial bacteria can occur in dogs and horses.{{cite web|url=https://www.whole-dog-journal.com/issues/7_3/features/Canine-Antibiotics_5612-1.html|title=The Dangers of Antibiotic Misuse and Your Dog - Whole Dog Journal|website=www.whole-dog-journal.com|date=29 January 2004|access-date=19 May 2017}}{{cite journal|last1=Costa|first1=Marcio C|last2=Stämpfli|first2=Henry R|last3=Arroyo|first3=Luis G|last4=Allen-Vercoe|first4=Emma|author-link4=Emma Allen-Vercoe|last5=Gomes|first5=Roberta G|last6=Weese|first6=J|year=2015|title=Changes in the equine fecal microbiota associated with the use of systemic antimicrobial drugs|url=|journal=BMC Veterinary Research|volume=11|issue=1|pages=19|doi=10.1186/s12917-015-0335-7|issn=1746-6148|pmc=4323147|pmid=25644524 |doi-access=free }}

Dogs may have side effects that include: joint pain, loss of appetite, vomiting, flatulence (intestinal gas), fungal infections and digestive problems.{{cite web|url=https://www.reference.com/science/correct-dosage-penicillin-dogs-7dfcff44fff7ef42|title=What is the correct dosage of penicillin for dogs?|date=4 August 2015 |access-date=19 May 2017}} 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.{{cn|date=March 2024}}

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.{{cite journal|last1=Kaplan|first1=Megan I.|last2=Lee|first2=Justine A.|last3=Hovda|first3=Lynn R.|last4=Brutlag|first4=Ahna|title=Adverse effects associated with inadvertent intravenous penicillin G procaine-penicillin G benzathine administration in two dogs and a cat|journal=Journal of the American Veterinary Medical Association|volume=238|issue=4|year=2011|pages=507–510|issn=0003-1488|doi=10.2460/javma.238.4.507|pmid=21320022|doi-access=free}}

Penicillin is known to become less effective as strains of bacteria become resistant.{{cite journal|last1=Li|first1=Shunming|last2=Huang|first2=Jingya|last3=Chen|first3=Zhiyao|last4=Guo|first4=Dan|last5=Yao|first5=Zhenjiang|last6=Ye|first6=Xiaohua|title=Antibiotic Prevention for Maternal Group B Streptococcal Colonization on Neonatal GBS-Related Adverse Outcomes: A Meta-Analysis|journal=Frontiers in Microbiology|volume=8|year=2017|page=374|issn=1664-302X|doi=10.3389/fmicb.2017.00374|pmid=28367139|pmc=5355432|doi-access=free}}

{{reflist}}

• {{cite book | last = Henry | first = Norma | title = RN nursing care of children : review module | publisher = Assessment Technologies Institute | location = Stilwell, KS | year = 2016 | isbn = 9781565335714 }}
• {{cite book | last = Karch | first = Amy | title = Focus on nursing pharmacology | publisher = Wolters Kluwer | location = Philadelphia | year = 2017 | isbn = 9781496318213 }}
• {{cite book | last = Potter | first = Patricia | title = Fundamentals of nursing | publisher = Mosby Elsevier | location = St. Louis, Mo | year = 2013 | isbn = 9780323079334 }}
• {{cite book | last = Vallerand | first = April | title = Davis's drug guide for nurses | publisher = F.A. Davis Company | location = Philadelphia | year = 2017 | isbn = 9780803657052 }}

{{Commons category|Penicillin antibiotics}}

• [https://web.archive.org/web/20090327130138/http://users.ox.ac.uk/~jesu1458/ Model of Structure of Penicillin, by Dorothy Hodgkin et al., Museum of the History of Science, Oxford]

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{{Hypersensitivity and autoimmune diseases|state=expanded}}

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Category:Microbiology

Side effects

Category:Medication side effects