Effects of penicillin g benzathine injection: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Main Research Findings

Benzathine penicillin G (BPG) is an antibiotic commonly used for the treatment of syphilis and as secondary prophylaxis for rheumatic heart disease (RHD). 20 、 15 、 13 、 11 、 3 、 8 、 16 、 5 、 3 、 7 However, it has been reported to cause a range of side effects. 18 、 15 One rare but serious side effect is Nicolau syndrome (NS). 10 、 4 、 12 、 21 、 19 、 9 This syndrome is characterized by severe pain, skin discoloration, and tissue necrosis at the injection site. 10 The severity of NS can vary, ranging from mild pain to severe complications such as sepsis and limb amputation. 10 、 9 NS is thought to occur due to inadvertent intravascular injection of BPG, leading to local ischemia and tissue damage. 9 There is also a growing concern about cardiovascular complications in patients with severe RHD following BPG injections. 7 These patients may be at increased risk for cardiovascular compromise and may benefit from oral prophylaxis instead. 7 Other research focuses on improving the delivery of BPG. 2 For example, studies are exploring subcutaneous infusion of high-dose BPG as a safer and more effective alternative to intramuscular injections. 2

Benefits and Risks

Benefit Summary

Benzathine penicillin G (BPG) is a vital antibiotic used for the treatment of syphilis and as a preventative measure against rheumatic heart disease (RHD). 20 、 15 、 13 、 11 、 3 、 8 、 16 、 5 、 3 、 7

Risk Summary

BPG can cause various side effects, including pain and swelling at the injection site. 18 、 15 It can also lead to Nicolau syndrome (NS), a rare but potentially severe condition characterized by tissue necrosis. 10 、 4 、 12 、 21 、 19 、 9 Furthermore, patients with severe rheumatic heart disease (RHD) may be at increased risk for cardiovascular complications following BPG injections. 7

Comparison Between Studies

Commonalities in Studies

Numerous studies have investigated the effects and side effects of benzathine penicillin G (BPG) injections. 20 、 15 、 13 、 11 、 3 、 8 、 16 、 5 、 3 、 7 The research encompasses various purposes, including treatment of syphilis and rheumatic fever, as well as secondary prevention of rheumatic heart disease (RHD). 20 、 15 、 13 、 11 、 3 、 8 、 16 、 5 、 3 、 7 Moreover, studies involve participants across various age groups, from children to adults. 20 、 15 、 13 、 11 、 3 、 8 、 16 、 5 、 3 、 7

Differences Between Studies

There are distinctions between studies in terms of the targeted disease, research methodology, and participant demographics. Some studies have examined the impact of varying BPG dosage and administration methods on treatment outcomes. 2 Others have focused on assessing the risk of serious side effects like Nicolau syndrome. 10 Furthermore, there are studies dedicated to evaluating the quality of BPG. 11 These discrepancies in study design can lead to varied results, highlighting the need for comprehensive interpretation of the collective findings.

Consistency and Discrepancies in Results

While several studies have consistently demonstrated the effectiveness of BPG for treating syphilis and rheumatic fever and for preventing RHD, 20 、 15 、 13 、 11 、 3 、 8 、 16 、 5 、 3 、 7 research also consistently underscores the potential for side effects, including injection site pain, swelling, and the rare but serious complication of Nicolau syndrome. 18 、 15 、 10 、 4 、 12 、 21 、 19 、 9 It is crucial to acknowledge both the benefits and risks associated with BPG, particularly in patients with severe RHD, who may be at higher risk for cardiovascular complications. 7

Considerations for Applying the Findings in Real-Life

While BPG is an effective treatment for syphilis and RHD, it is crucial to be aware of its potential side effects. 20 、 15 、 13 、 11 、 3 、 8 、 16 、 5 、 3 、 7 Before receiving BPG, it is essential to discuss the potential risks with a healthcare professional. 18 、 15 、 10 、 4 、 12 、 21 、 19 、 9 They can assess individual needs and determine the most appropriate course of action, including whether BPG is the right choice or if alternative treatments should be considered. 18 、 15 、 10 、 4 、 12 、 21 、 19 、 9 Close monitoring for any potential side effects is crucial after receiving BPG injections. 18 、 15 、 10 、 4 、 12 、 21 、 19 、 9 Prompt medical attention is essential if any concerning symptoms arise.

Limitations of Current Research

Research on BPG, particularly regarding the rare but serious complication of Nicolau syndrome, is still limited. 10 、 4 The understanding of its underlying mechanisms and potential preventive measures is not yet fully developed. 10 、 4 Furthermore, long-term observational studies are needed to assess the impact of BPG injections on patients with severe rheumatic heart disease. 7

Future Research Directions

To gain a more comprehensive understanding of the safety and efficacy of BPG, further research is crucial. 20 、 15 、 13 、 11 、 3 、 8 、 16 、 5 、 3 、 7 Strengthening research on Nicolau syndrome is paramount, with a focus on unraveling its mechanisms and developing preventive strategies. 10 、 4 Long-term observational studies are needed to evaluate the long-term effects of BPG injections on patients with severe rheumatic heart disease. 7 Such research endeavors hold the promise of establishing safer and more effective practices for utilizing BPG, ultimately minimizing risks for patients.

Conclusion

Benzathine penicillin G (BPG) is a valuable antibiotic for syphilis and RHD treatment and prevention. 20 、 15 、 13 、 11 、 3 、 8 、 16 、 5 、 3 、 7 However, it is crucial to be aware of its potential side effects, including Nicolau syndrome, which can be serious. 18 、 15 、 10 、 4 、 12 、 21 、 19 、 9 Patients with severe RHD may be at higher risk for cardiovascular complications. 7 Therefore, consulting a healthcare professional is essential before receiving BPG injections to discuss potential risks and determine the most appropriate treatment approach. 18 、 15 、 10 、 4 、 12 、 21 、 19 、 9 Furthermore, ongoing research is crucial for a deeper understanding of BPG’s safety and efficacy, particularly in regard to Nicolau syndrome and its impact on patients with severe RHD. 10 、 4 、 7

Literature analysis of 22 papers
Positive Content
11
Neutral Content
3
Negative Content
8
Article Type
3
0
0
3
16
1.

Penicillamine in rheumatoid arthritis. A problem of toxicity.

Author: TaylorH G, SamantaA

Rheumatoid arthritis treatment
Autoimmune syndromes
Gastrointestinal events
Leukopenia
Proteinuria
Skin rash
Thrombocytopenia

Penicillamine, a disease-modifying antirheumatic drug, is effective in treating rheumatoid arthritis but its use is limited by toxicity. Common adverse effects include proteinuria, skin rashes, gastrointestinal events, and thrombocytopenia or leucopenia.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

3.

Development of a sustained release implant of benzathine penicillin G for secondary prophylaxis of rheumatic heart disease.

Author: BarrRenae K, BarberBryce W, TaitJessica R, LandersdorferCornelia B, SalmanSam, MuskGabrielle C, Page-SharpMadhu, BattyKevin T, KadoJoseph, ManningLaurens, CarapetisJonathan R, BoydBen J

RHD prophylaxis
Sustained penicillin release

Intramuscular benzathine penicillin G (BPG) injections are the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis, but adherence is poor. An implant that provides sustained penicillin concentrations for more than six months is needed to improve adherence.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

[Nicolau syndrome].

Author: Rodríguez AriasEdwin A, SolaMaría Fernanda, De Arza PochylakLorea, MolinaMaría Florencia, AranaSantiago, AlfaroCarmen T

Nicolau syndrome

Nicolau syndrome is a rare complication that can occur after intramuscular injection of certain drugs. It causes pain, edema, erythema, and eventually a necrotic plaque. This case report describes a 31-year-old male who developed Nicolau syndrome after receiving benzathine penicillin. The patient responded well to treatment with enoxaparin and cilostazol.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
English AbstractA summary of a research paper/publication written in English for a wider audience.

Language : Spanish

5.

Population pharmacokinetic study of benzathine penicillin G administration in Indigenous children and young adults with rheumatic heart disease in the Northern Territory, Australia.

Author: KadoJoseph, SalmanSam, HandRobert, O'BrienMargaret, RalphAnna, BowenAsha C, Page-SharpMadhu, BattyKevin T, DolmanVeronica, FrancisJoshua R, CarapetisJonathan, ManningLaurens

Benzathine penicillin G is a key medication for preventing rheumatic heart disease. However, there is limited pharmacokinetic data available for children and adolescents at high risk for this disease, which makes it difficult to determine the optimal dosage and frequency of injections.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Spinal cord ischaemia following the gluteal injection of Benzathine benzylpenicillin.

Author: OsmanSuha A N, SwarnaShyam S, Russell-HobbsKate, HariharanSankar, BabikerAyah M

Bowel and bladder incontinence
Paralysis
Spinal cord injury

This case report describes a 25-year-old man who developed anterior spinal cord syndrome following a benzathine benzylpenicillin injection. This rare complication is thought to be caused by embolism of the penicillin products, which can travel retrogradely through the superior gluteal artery and cause infarction to the anterior part of the spinal cord.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

7.

Penicillin Reactions in Patients With Severe Rheumatic Heart Disease: A Presidential Advisory From the American Heart Association.

Author: SanyahumbiAmy, AliSulafa, BenjaminIvor J, KarthikeyanGanesan, OkelloEmmy, SableCraig A, TaubertKathryn, WyberRosemary, ZuhlkeLiesl, CarapetisJonathan R, BeatonAndrea Z,

BPG prophylaxis
BPG adverse effects

This advisory discusses the risks of cardiovascular compromise in patients with rheumatic heart disease receiving benzathine penicillin G (BPG) injections for secondary antibiotic prophylaxis. The advisory recommends risk stratification and strategies for risk reduction, including considering oral prophylaxis for patients with elevated risk.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

8.

High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease.

Author: KetemaEzra B, GishenNigus Z, HailuAbraha, LeulAbadi, HadguAbera, HagosKiflom, BerhaneSamual, TsegaTemesgen, Page-SharpMadhu, DavisTimothy Me, MooreBrioni, BattyKevin T, CarapetisJonathan, SalmanSam, ManningLaurens

ARF prevention
RHD prevention
Inter-ethnic variability
Preparation variability

Benzathine penicillin G (BPG) injections are crucial for preventing rheumatic heart disease (RHD) following rheumatic fever. This study highlights the need for further research to understand the variability in BPG injections across different populations and to determine optimal dosing strategies for effective RHD prevention.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Nicolau syndrome following intramuscular benzathine penicillin injection: a case report.

Author: PhiriWalaza, MusondaMaen Shulammite, KyakilikaKebby, MiyobaMichelo Haluuma, MalumaniMalan

Limb amputation
Nicolau syndrome

This case report describes a five-year-old girl who developed Nicolau syndrome (NS) following an intramuscular injection of benzathine penicillin. The case resulted in above-the-knee amputation, highlighting the importance of considering NS in patients receiving intramuscular injections.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

11.

Quality of benzathine penicillin G: A multinational cross-sectional study.

Author: HandRobert M, SenarathnaS M D K Ganga, Page-SharpMadhu, GrayKatherine, Sika-PaotonuDianne, SheelMeru, ChuangVictor T G, MartinezJorge, LunaGiuseppe, ManningLaurens, WyberRosemary, CarapetisJonathan R, BattyKevin T

RHD prophylaxis
Syphilis treatment

Benzathine penicillin G (BPG) is used to treat syphilis and rheumatic heart disease. The study found that current batches of BPG are of satisfactory quality. However, a modest proportion of samples contained aggregated particles. Future studies should focus on the physical characteristics of BPG, as these may contribute to variations in plasma penicillin concentrations and needle blockages.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Nicolau Syndrome, Masquerader of Postinjection Sciatic Nerve Injury: Case Report and Review of Literature.

Author: RajuBharath, AshrafOmar, JumahFareed, Appaji GowdaNaveen Mandya, GuptaGaurav, SunHai, NandaAnil

Nicolau syndrome treatment
Nicolau syndrome
injection palsy

Nicolau syndrome, a rare and potentially underdiagnosed condition that can be mistaken for injection palsy, should be considered before diagnosing sciatic nerve injury after intramuscular gluteal injection. Early diagnosis and appropriate treatment are crucial.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Video-Audio MediaMedia that combines video and audio. Includes movies, TV shows, and online videos.

Language : English

13.

Tinidazole: Another Therapeutic Option for Syphilis?

Author: DragoFrancesco, CiccareseGiulia, ReboraAlfredo, ParodiAurora

Syphilis lesion improvement
Tinidazole treatment

Tinidazole, an antibiotic similar to metronidazole, was found to improve lesions in patients with early syphilis. While this observation needs further investigation, tinidazole might be an alternative for penicillin-allergic patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

15.

Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial.

Author: EstradaVicente, SantiagoEva, CabezasInmaculada, CotanoJuan Luis, CarrióJuan Carlos, Fuentes-FerrerManuel, VeraMar, AyerdiOskar, RodríguezCarmen, LópezLaura, CabelloNoemí, NúñezMaría José, PuertaTeresa, SagastagoitiaIñigo, Del RomeroJorge

Syphilis treatment
Pain at injection site

This study aims to identify less painful ways of administering intramuscular (IM) penicillin G benzathine (PGB) in the treatment of syphilis in adults.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

16.

A population pharmacokinetic study of benzathine benzylpenicillin G administration in children and adolescents with rheumatic heart disease: new insights for improved secondary prophylaxis strategies.

Author: HandRobert M, SalmanSam, NewallNelly, VineJulie, Page-SharpMadhu, BowenAsha C, GrayKatherine, BakerAmy, KadoJoseph, JosephJohn, MarshJulie, RamsayJames, Sika-PaotonuDianne, BattyKevin T, ManningLaurens, CarapetisJonathan

RHD prevention
Rheumatic fever prevention

This study investigated the pharmacokinetics of benzylpenicillin, a metabolite of benzathine benzylpenicillin G (BPG), in populations at risk of rheumatic heart disease (RHD). BPG is recommended as secondary prophylaxis to prevent RHD recurrence.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Aseptic myonecrosis following intramuscular benzathine penicllin G injection: a novel syndrome.

Author: RyanNicholas, OlsonAndrew

Aseptic myonecrosis

This report describes a rare case of aseptic myonecrosis in a child following an intramuscular (IM) injection of benzathine penicillin G. The authors highlight the importance of recognizing this potentially serious complication of IM injections.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

19.

[Nicolau livedoid dermatitis with severe neurological involvement in a child].

Author: ElfatoikiF-Z, EnnajdiA, GueddariW, ChihebS

Necrosis
Tissue ischemia

A 10-year-old male child presented with Nicolau syndrome following gluteal intramuscular injection of benzathine-penicillin. Treatment was based on fluid expansion, intravenous steroids, and anticoagulants, resulting in improvement of cutaneous and muscular lesions. Improvement in terms of neurological dysfunction was obtained after regular neuromuscular rehabilitation.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : French

20.

A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana.

Author: Kwakye-MacleanCynthia, AganaNsiire, GyapongJohn, NorteyPriscilia, Adu-SarkodieYaw, AryeeEsther, AsieduKingsley, BallardRoland, BinkaFred

Oral azithromycin efficacy
Yaws treatment
Intramuscular injection pain
Safety concerns

This study compared the efficacy of a single oral dose of azithromycin to intramuscular benzathine penicillin for the treatment of yaws, a treponemal infection that has re-emerged in several countries. Oral azithromycin may offer a safer and more convenient treatment option than intramuscular injections.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

21.

Acute Transverse Myelitis and Nicolau Syndrome after Benzathine Penicillin Injection.

Author: RajadhyakshaGirish, LimayeCharulata, MeahAmeena, GaikwadSushma, JainShubham

Nicolau syndrome
Transverse myelitis

Nicolau syndrome is a rare condition that can occur after an injection. This study presents a case report of a patient who developed Nicolau syndrome and transverse myelitis after receiving a benzathine penicillin injection.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

22.

Anticoagulant and vasodilator therapy for Nicolau syndrome following intramuscular benzathine penicillin injection in a 4 year old boy.

Author: Alkan BozkayaTijen, DemirelGamze, OrmeciTugrul, AlSerdar, ÇakarEngin, TastekinAyhan, TurkogluHalil

Ischemic necrosis

Nicolau syndrome, a rare complication of benzathine penicillin injection, can be treated successfully with unfractionized heparin and pentoxifylline.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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