What are the key differences between Rocephin and Penicillin for antibiotic prophylaxis. How do these antibiotics compare in efficacy and cost-effectiveness. Which antibiotic regimen is more suitable for compound mandible fractures.

Understanding Rocephin and Penicillin: A Comparative Analysis

Rocephin (ceftriaxone) and Penicillin are two widely used antibiotics in medical practice, each with its own unique properties and applications. While both are effective in treating various bacterial infections, they differ in their chemical structure, mechanism of action, and spectrum of activity.

Rocephin belongs to the cephalosporin class of antibiotics, specifically a third-generation cephalosporin. Penicillin, on the other hand, is the progenitor of the beta-lactam antibiotic class. Despite their differences, both antibiotics work by interfering with bacterial cell wall synthesis, ultimately leading to bacterial cell death.

Key Differences Between Rocephin and Penicillin

• Spectrum of activity: Rocephin has a broader spectrum of activity compared to Penicillin
• Resistance: Many bacteria have developed resistance to Penicillin, while Rocephin remains effective against a wider range of pathogens
• Administration: Rocephin is typically given once daily, while Penicillin often requires more frequent dosing
• Cost: Rocephin is generally more expensive than Penicillin

Efficacy of Rocephin and Penicillin in Antibiotic Prophylaxis

In the context of antibiotic prophylaxis for compound mandible fractures, both Rocephin and Penicillin have shown effectiveness. The study conducted by Heit et al. aimed to compare the efficacy of these two antibiotics in preventing post-operative infections.

The research involved 90 patients with compound mandible fractures, randomly assigned to two groups: one receiving 1 gram of ceftriaxone (Rocephin) daily, and the other receiving 2 million units of Penicillin G every 4 hours.

Study Results

The outcomes of the study revealed that both antibiotic regimens were equally effective in preventing post-operative infections. In each group, only two patients developed infections within the first two weeks of treatment. These infections were successfully resolved with local wound care, removal of internal fixation devices, and oral antibiotics.

Cost-Effectiveness: Rocephin vs Penicillin

While both antibiotics demonstrated similar efficacy, the cost difference between the two treatment regimens was significant. The study revealed that using Rocephin resulted in a cost savings of approximately $350 per day compared to the Penicillin regimen.

This substantial cost difference can be attributed to several factors:

• Frequency of administration: Rocephin’s once-daily dosing requires less staff time and resources compared to Penicillin’s every 4-hour dosing schedule
• Duration of treatment: The study does not specify the exact duration, but typically, antibiotic prophylaxis for compound fractures lasts several days
• Associated costs: Fewer administrations may result in reduced costs for IV supplies, nursing time, and potential complications from frequent IV access

Advantages of Rocephin in Antibiotic Prophylaxis

The study’s findings highlight several advantages of using Rocephin (ceftriaxone) for antibiotic prophylaxis in compound mandible fractures:

1. Equivalent efficacy to Penicillin in preventing post-operative infections
2. Significant cost savings, making it a more economical choice for healthcare systems
3. Once-daily dosing, which can improve patient compliance and reduce the burden on healthcare staff
4. Broader spectrum of activity, potentially covering a wider range of potential pathogens

Considerations for Antibiotic Selection in Compound Mandible Fractures

While the study demonstrates the advantages of Rocephin, it’s important to consider various factors when selecting an antibiotic for prophylaxis in compound mandible fractures:

• Patient allergies: Some patients may have allergies to cephalosporins or penicillins
• Local antibiotic resistance patterns: The prevalence of resistant bacteria can vary by region
• Patient-specific factors: Comorbidities, immune status, and other individual characteristics may influence antibiotic choice
• Institutional protocols: Some healthcare facilities may have specific guidelines for antibiotic prophylaxis

Potential Implications for Clinical Practice

The findings of this study have several potential implications for clinical practice in the management of compound mandible fractures:

1. Cost-effective prophylaxis: Healthcare providers may consider using Rocephin as a first-line antibiotic for prophylaxis in suitable patients
2. Streamlined care: The once-daily dosing of Rocephin can simplify patient care and potentially reduce hospital stays
3. Resource allocation: The cost savings associated with Rocephin use could allow for better allocation of healthcare resources
4. Patient satisfaction: Fewer antibiotic administrations may lead to improved patient comfort and satisfaction

Future Research Directions

While this study provides valuable insights into the use of Rocephin for antibiotic prophylaxis in compound mandible fractures, several areas warrant further investigation:

• Long-term outcomes: Studies examining the long-term effects of different antibiotic regimens on fracture healing and complications
• Antibiotic resistance: Research on the potential development of antibiotic resistance with prolonged prophylaxis
• Comparative studies: Investigations comparing Rocephin to other broad-spectrum antibiotics for prophylaxis in various types of fractures
• Cost-benefit analysis: More comprehensive analyses of the overall economic impact of different antibiotic regimens in fracture management

Practical Recommendations for Healthcare Providers

Based on the study findings and current understanding of antibiotic prophylaxis in compound mandible fractures, healthcare providers may consider the following recommendations:

1. Evaluate patient-specific factors: Consider allergies, comorbidities, and other individual characteristics when selecting an antibiotic regimen
2. Consider Rocephin as a first-line option: For suitable patients, Rocephin offers equivalent efficacy to Penicillin with significant cost savings
3. Monitor for infections: Regardless of the antibiotic chosen, closely monitor patients for signs of post-operative infections, especially in the first two weeks
4. Follow-up care: Ensure proper follow-up care, including regular check-ups and removal of fixation devices when appropriate
5. Stay informed: Keep up-to-date with local antibiotic resistance patterns and institutional guidelines for antibiotic prophylaxis

The choice between Rocephin and Penicillin for antibiotic prophylaxis in compound mandible fractures should be based on a careful consideration of efficacy, cost-effectiveness, and patient-specific factors. While this study demonstrates the potential advantages of Rocephin, it’s crucial to approach each case individually and make informed decisions based on the best available evidence and clinical judgment.

As research in this field continues to evolve, healthcare providers should remain open to new findings and be prepared to adjust their practices accordingly. The goal remains to provide optimal care for patients with compound mandible fractures while managing healthcare resources effectively.

By carefully weighing the benefits and considerations of different antibiotic regimens, healthcare providers can ensure that patients receive the most appropriate and effective prophylaxis for their specific needs. This approach not only improves patient outcomes but also contributes to the responsible use of antibiotics and healthcare resources in the broader context of medical practice.

Comparison of ceftriaxone with penicillin for antibiotic prophylaxis for compound mandible fractures

Clinical Trial

. 1997 Apr;83(4):423-6.

doi: 10.1016/s1079-2104(97)90139-6.

J M Heit 
¹
, M R Stevens, K Jeffords

Affiliations

Affiliation

• ¹ University of Miami Medical School, Jackson Memorial Hospital, Florida, USA.

• PMID:

  9127371

• DOI:

  10.1016/s1079-2104(97)90139-6

Free article

Clinical Trial

J M Heit et al.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod.

1997 Apr.

Free article

. 1997 Apr;83(4):423-6.

doi: 10.1016/s1079-2104(97)90139-6.

Authors

J M Heit 
¹
, M R Stevens, K Jeffords

Affiliation

• ¹ University of Miami Medical School, Jackson Memorial Hospital, Florida, USA.

• PMID:

  9127371

• DOI:

  10.1016/s1079-2104(97)90139-6

Abstract

Purpose:

The purpose of the study was to compare the efficacy and cost of two antibiotic regimens for prophylaxis of compound mandible fractures: 1 gm/day ceftriaxone and 2 million U penicillin G every 4 hours.

Design:

A prospective study of 90 patients with compound mandible fractures was performed. The patients were randomized to the two antibiotic regimens. The surgical procedures were performed by oral/maxillofacial surgery residents at a large urban training center. Standard treatment consisted of open reduction with either bone plates or wires, with all patients receiving 6 weeks of maxillomandibular fixation. The patients were monitored at 2-week intervals for 8 weeks by two of the authors, who were blinded to which antibiotic regimen the patient was assigned.

Results:

Two patients in each group had postoperative infections within the first 2 weeks of treatment. The infections resolved with local wound care, removal of internal fixation devices, and oral antibiotics. After resolution of the infection each patient had a malunion, which was managed without additional complications. The cost difference between the two treatment regimens was approximately $350 per day.

Conclusion:

Ceftriaxone was noted to be an efficacious and cost-effective treatment alternative to penicillin G for compound mandible fracture antibiotic prophylaxis.

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Cephalosporin administration with a penicillin allergy history

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Question:

2/2/2016

Is it safe to administer cephalosporins in a penicillin allergic patient? Assuming a true recent IgE mediated type reaction to PCN with + PCN skin test and never took any cephalosporins in the past. Recent studies by Macy et al 2009 and 2011 say that the rate of cross reaction between PCN and cephalosporin is 1% and the same as the background prevalence of each. Local hospitals are removing the cross reaction risk and allowing patients with a prior PCN allergy to be allowed to prescribe cephalosporins to these patients. I thought the risk was higher, and more precaution should be undertaken, such as a cephalosporin skin test or challenge.

Answer:

The difficulty in answering your question is the meaning of “safe” and the meaning of “penicillin allergic patient”. The medical literature suggests there is greater risk in giving cephalosporin, particularly first generation cephalosporin, to a patient with a history of penicillin allergy than to a patient without penicillin allergy (2-4 fold increased risk). (Romano; Kelkar; Mirakian) However, other analyses minimize risk. (Annè, Macy) Finally there is evidence of increased risk for any medication, irrespective of structure similarities or cross-reactivity, if there is history of prior drug reaction (Strom).

Some quotes from the 2010 Practice Parameter for Drug Allergy with evidence basis provided in parenthesis are:

1. Penicillin

Summary Statement 71: Approximately 10% of patients report a history of penicillin allergy, but  after complete evaluation, up to 90% of these individuals are able to tolerate penicillins. (B)

3. Cephalosporins

Summary Statement 92: The overall reaction rate to cephalosporins is approximately 10-fold lower than it is for penicillin. (C) Summary Statement 93: Most hypersensitivity reactions to cephalosporins are probably directed at the R-group side chains rather than the core beta-lactam portion of the molecule. (D) Summary Statement 94: Skin testing with native cephalosporins is not standardized, but a positive skin test result using a nonirritating concentration suggests the presence of drug specific IgE antibodies. (D) A negative skin test result does not rule out an allergy because the negative predictive value is unknown. (D) Summary Statement 95: Patients with a history of an immediate-type reaction to 1 cephalosporin should avoid cephalosporins with similar R-group side chains. (D) Treatment with cephalosporins with dissimilar side chains may be considered, but the first dose should be given via graded challenge or induction of drug tolerance, depending on the severity of the previous reaction. (D) Summary Statement 96: Cephalosporins and penicillins share a common beta-lactam ring structure and moderate crossreactivity has been documented in vitro. (B)

4. Cephalosporin administration to patients with a history of penicillin allergy

Summary Statement 97: Since 1980, studies show that approximately 2% of penicillin skin test–positive patients react to treatment with cephalosporins, but some of these reactions may be anaphylactic reactions. (C) Summary Statement 98: Without preceding penicillin skin testing, cephalosporin treatment of patients with a history of penicillin allergy, selecting out those with severe reaction histories, show a reaction rate of 0. 1% based on recent studies. (C) Summary Statement 99: Penicillin skin testing, when available, should be considered before administration of cephalosporins in patients with a history of penicillin allergy. (E) Summary Statement 100: Patients who have a history of a possible IgE-mediated reaction to penicillin, regardless of the severity of the reaction, may receive cephalosporins with minimal concern about an immediate reaction if skin test results for penicillin major and minor determinants are negative. (B) Summary Statement 101: Treatment options for penicillin skin test–positive patients include (1) administration of an alternate (non–beta-lactam) antibiotic, (2) administration of cephalosporin via graded challenge, or (3) administration of cephalosporin via rapid induction of drug tolerance. (E) Summary Statement 102: Skin testing to the cephalosporin followed by graded challenge appears to be a safe method for administration of some cephalosporins in penicillin allergic patients. (B) Summary Statement 103: If penicillin and cephalosporin skin testing is unavailable, depending on the reaction history, cephalosporins may need to be given via graded challenge or rapid induction of drug tolerance. (E)

Most of the evidence is opinion or consensus but the highest level of evidence for administration of cephalosporin to a patient with penicillin allergy is “minimal concern” if the penicillin and major determinant skin test are negative and if graded challenge is used with the cephalosporin following a negative skin test with the same drug. This is consistent with the British guidelines (Mirakian).

In summary, most patients who report penicillin allergy are not allergic and most patients with documented specific-IgE to penicillin can tolerate cephalosporin, since the majority of cephalosporin immunologic reactions are to the side-chain (Ledford). However, the package insert of cephalosporins list penicillin allergy as a warning for administration, and there is an increased risk of cephalosporin reaction with a documented penicillin allergy (example from ceftriaxone).

“Hypersensitivity:

BEFORE THERAPY WITH CEFTRIAXONE IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS, PENICILLINS OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE THE USE OF SUBCUTANEOUS EPINEPHRINE AND OTHER EMERGENCY MEASURES.”

The increased risk of using a cephalosporin with a penicillin allergy may be considered modest or may be considered inconsequential, depending if your perspective is a legalistic, maximal risk avoidance strategy vs a practical approach of treating when the risk is not prohibitive, however that is defined. The estimates for a cephalosporin reaction are probably 1-3% with a history of penicillin allergy, which is probably slightly greater than the general population, but the severity of the reaction may be greater with a documented penicillin allergy. I would not feel comfortable with administering cephalosporin to a patient with a convincing history of IgE- mediated penicillin allergy without documenting a discussion with the patient of the increased risk and the option of testing and performing a graded challenge to further reduce the risk (Mirakian). Otherwise, any adverse effect that appears immunologic could be viewed as a deviation from the standard of care per the FDA product label. I do not think it is advisable to have a blanket policy to administer cephalosporin without assessment of the individual risk and documentation of patient discussion with a knowledgeable professional. Otherwise, I would feel the patient has grounds for recourse if an adverse event occurs, irrespective of causation.

1. Romano, Antonino, et al. “Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins.” Annals of Internal Medicine 141.1 (2004): 16-22.

2. Kelkar, Pramod S., and James T-C. Li. “Cephalosporin allergy.” New England Journal of Medicine 345.11 (2001): 804-809.

3. Annè, Suresh, and Robert E. Reisman. “Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy.”Annals of Allergy, Asthma & Immunology: official publication of the American College of Allergy, Asthma, & Immunology 74. 2 (1995): 167-170.

4. Ledford DK. Cephalosporin side chain cross-reactivity. J Allergy Clin Immunol Pract 2015;3:1006-7

5. Strom, Brian L., et al. “Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics.” New England Journal of Medicine 349.17 (2003): 1628-1635.

6. Campagna, James D., et al. “The use of cephalosporins in penicillin-allergic patients: a literature review.” The Journal of Emergency Medicine 42.5 (2012): 612-620.

Mirakian, R., et al. “BSACI guidelines for the management of drug allergy.” Clinical & 7. Experimental Allergy 39.1 (2009): 43-61.

7. Macy, Eric. “Penicillin and beta-lactam allergy: epidemiology and diagnosis.” Current Allergy and Asthma Reports 14.11 (2014): 1-7.

8. Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med 2003;349:1628-35.

I hope this information is of help to you and your practice.

All my best.

Dennis K. Ledford, MD, FAAAAI

Modern problems of treatment of syphilitic infection uMEDp

Syphilis appeared in Europe five hundred years ago. Methods for the treatment of this disease have come a long way from long-term and ineffective therapy with highly toxic drugs of heavy metals to highly effective and short-term therapy with antibiotics. The last stage began relatively recently – from the mid-1940s. XX century, when penicillin began to be used in the treatment of this disease, which showed fantastic efficacy in combination with excellent tolerability (side effects were limited only to occasional allergic reactions).

Historical digression

Since the beginning of their use in the treatment of syphilis, penicillin preparations have been presented in the form of three different salts – water-soluble (sodium), medium duration (novocaine, procaine) and duration – dibenzylethylenediamine. Each of them has its own advantages and disadvantages in the treatment of syphilis. The sodium salt of penicillin gives a high peak concentration of the antibiotic in the blood serum: up to 15.0–20.0 μg / ml, on average – 2.7 μg / ml after 30 minutes. after the administration of the drug, which exceeds the MTC for T.pallidum in 539times [1]. A high peak concentration is considered a favorable factor, since the drug actively affects the causative agent of syphilis – pale treponema. The disadvantage is the relatively rapid elimination of the drug: 6 hours after intramuscular injection of 1 million U, the concentration of penicillin exceeds the MTC by an average of 33 times, and then drops to zero values, which requires four injections of the drug per day. Smaller doses require even more frequent administration, which is possible only with inpatient treatment.

Durant preparations (benzathine benzylpenicillins) create a long-term (within several days, up to 18–21 days after a single injection at a dose of 2. 4 million units), but a low concentration of penicillin in the body: a peak after 3 hours, an average of 0.19 μg/ml, the average concentration before the next injection is 0.05 μg/ml [1]. Fortunately, treponema pallidum retained its high sensitivity to penicillin, and the minimum therapeutic level (0.018 µg/ml) is still surpassed. However, an excess of MTK in blood serum by 6–10 times is considered optimal, which ensures the maximum treponemicidal effect. At the same time, durant forms of penicillin poorly overcome the BBB, and therefore, with undiagnosed latent syphilitic meningitis, cerebrospinal fluid sanitation is not achieved and the possibility of developing late manifest forms of neurosyphilis remains.

The drug of “medium” duration (procaine-penicillin) gives a relatively high peak (on average 3.1 μg / mg 2 hours after administration at a dose of 1.2 million units) and provides a fairly high concentration of penicillin in the blood serum during the day after administration, by the end of which the concentration decreases to 0. 6 µg/ml [1, 2]. Thus, procaine-penicillin, administered once a day, is suitable for both inpatient and outpatient treatment. The domestic drug of this series, the novocaine salt of penicillin, showed significant fluctuations in the concentration of the antibiotic in the blood serum, and in most patients, after administration at a dose of 1.2 million IU, it did not provide treponemicidal levels after 24 hours [3]. This was the reason for the recommendation to administer the drug 2 times a day, 600 thousand units. Of course, this option already excluded the possibility of outpatient use and could only be used in a hospital.

Preparations of “medium” duration experienced two rises in popularity: in the late 50s – early 60s. (many venereologists of the old generation still regret the disappearance of such a drug as ecmonovocillin) and in the 90s, when procaine-penicillin was widely used in Russia, especially in Moscow and St. Petersburg. Unfortunately, repeated injections of this drug can lead to a very unpleasant complication – the so-called “procaine psychosis”, or Hoigne’s syndrome [4]. It is believed that this happens in 6 cases out of 1000, but practice has shown that it happens more often. The reason for the development of the syndrome is considered the direct effect of procaine on the limbic structures of the brain. Its symptoms frighten both the patient and the doctor: “at the tip of the needle”, the patient has ringing in the ears, severe weakness and a panic fear of death against the background of high blood pressure. There are known moments that predispose to the occurrence of this complication: traumatic brain injury, mental illness, a history of “panic attacks”, childhood and old age, violation of the technique of drug administration (hasty dilution of the powder, too rapid administration of the drug with its entry into the bloodstream). Taking into account the above circumstances could significantly reduce the frequency of such complications. Interestingly, durant penicillin preparations do not have such a side effect.

The positive qualities of various salts of penicillin back in the 50s. of the last century, they tried to combine in the so-called combined preparations of penicillin – bicillins: Bicillin-3, Bicillin-5, which are still used in practice, as well as Bicillin-6, Bicillin-122, which have not received distribution. All these drugs represent the ratio of the above salts of penicillin in different proportions. In particular, Bicillin-3 consists of three salts of penicillin in a ratio of 1:1:1, Bicillin-5 does not contain a sodium salt, and novocaine and dibenzylethylenediamine salts are related as 1:4.

Taking into account the composition and pharmacokinetics of these drugs, the frequency of their intramuscular administration is:

• for water-soluble penicillin – 4-8 times a day, depending on the dose;
• for durant penicillin – 1 time in 7 days;
• for novocaine (procaine) salt – 1 time per day:
• for both combined preparations – 2 times a week.

During the epidemic of the 90s-2000s. with a peak incidence at 1997 (277.3 cases per 100,000 population) in Russia, all of the listed options for penicillin preparations were available for the treatment of syphilis. In particular, durant preparations, which played a large positive role in stopping the incidence of early forms of syphilis: foreign Extencillin, Retarpen and the domestic analogue Bitsillin-1; preparations of “medium” duration: procaine-penicillin and novocaine salt of penicillin. Combined drugs were only domestically produced (Bicillin-3, Bicillin-5), although some of their analogues exist in Europe.

Domestic preparations of penicillin – durant and “medium” durant – were used less frequently: due to the outdated technology of their production, the concentration of the antibiotic is subject to significant fluctuations, so it is necessary to increase both the number of injections and the frequency of their administration. These drugs are administered intramuscularly in the form of a suspension, two-stage, to avoid getting into the vessel. The novocaine salt of penicillin and bicillins are unevenly dispersed, which can create some difficulties in their administration (needle blockage). Having finished reviewing the available penicillin preparations, we confirm that penicillin remains the drug of choice in the treatment of syphilis.

What is the current situation with the use of these drugs, in which cases which of them are indicated, do they remain relevant in the practice of a syphilidologist?

Modern drugs for the treatment of syphilis

In the past, when in Russia all patients with syphilis, regardless of the form of the disease, were hospitalized, the most common drug in the treatment of this infection was penicillin sodium, administered intramuscularly, first 8, and then 4 times per day, depending on the dose.

In the 1990s Durant preparations of penicillin dominated, which were very convenient to use and made it possible to treat patients on an outpatient basis. Durant preparations, in fact, made it possible to provide treatment for a huge number of patients and stop the epidemic, interrupting the epidemiological “chains”.

Over time, it turned out that a fairly significant number of patients with a disease duration of more than 12 months remained seroresistant (15.7% after treatment of secondary and 21.6% – latent early syphilis), and some even had clinical and serological relapses, which amounted to 7.7% and 28% of all treatment failures, respectively. Treatment with water-soluble penicillin in patients with similar forms of syphilis and the duration of the disease gave a significantly lower number of failures (the difference is statistically significant) [5]. Similar data have been obtained in other studies indicating that the maximum number of treatment failures occurs in individuals treated with benzathine benzylpenicillins [1]. Drugs of “medium” duration (procaine-penicillin), although they were used during the epidemic, were not widely used, and in the 2000s. completely disappeared from the pharmaceutical market due to the termination of purchases.

Meanwhile, for each of the three types of penicillin preparations: soluble, medium duration and duration – there are indications for the treatment of syphilis.

Water-soluble penicillin is indicated primarily for neurosyphilis – both at an early and late stage, optimally – in the form of infusions (generally accepted method – 2 infusions per day of 10-12 million units in 400.0 ml of saline with a duration of administration of 1 .5–2 hours). It is also most effective in the treatment of pregnant women, since it ensures sufficient penetration of the antibiotic into the amniotic fluid and fetal tissues, and in the treatment of children with both congenital and acquired syphilis. In addition, indications for the appointment of water-soluble penicillin are primary syphilis complicated by a secondary infection (phimosis, gangrenization) and the so-called “malignant” course of secondary syphilis (pustular syphilis, alopecia, leukoderma). All of these cases are an indication for hospitalization, which creates the necessary conditions for penicillin therapy.

With latent forms of syphilis, hospitalization is undesirable for the patient, and treatment with durant drugs does not create a sufficiently high concentration of the antibiotic in the body. For these cases, from our point of view, outpatient therapy with procaine-penicillin is most suitable, of course, in the absence of pathological changes in the cerebrospinal fluid. Since lumbar puncture is indicated for latent forms of syphilis, the detection of pathology in the CSF serves as a fairly weighty argument in choosing between water-soluble penicillin and procaine-penicillin. However, as mentioned above, there is no procaine-penicillin on the Russian market, and novocaine salt, due to its pharmacokinetic features, must be administered not once, but twice a day, i.e. again in a hospital. In this case, it is better to dwell on the sodium, soluble salt of penicillin.

Durant preparations are optimal for preventive treatment, treatment of primary syphilis, they can also be used in the treatment of secondary fresh syphilis, i.e. in the presence of remnants of chancre, regional lymphadenitis and generalized rash. Over the past year, supplies to the pharmacy network of Extencillin and Retarpen have been stopped. There is a possibility that they, like procaine-penicillin, will soon disappear from practice.

Bicillins, both mono (Bicillin-1) and combined (Bicillin-3 and Bicillin-5), are inferior to Extencillin and Retarpen in terms of pharmacokinetic characteristics. Because of this, they are administered at shorter intervals and a greater number of injections per course, which reduces compliance. In addition, the combination of two or three salts of penicillin, each of which is included in the combined preparation in a small dose, does not give the expected advantages in either concentration level or duration.

Nevertheless, the production of these preparations, apparently, should not be completely abandoned, since there is a danger of stopping the purchase of foreign durant penicillins, and they will disappear from the market, like procaine-penicillin.

Consider a group of reserve drugs in the treatment of syphilis. The most popular and most effective of these is the third-generation cephalosporin, ceftriaxone. According to the mechanism of action, it is close to penicillin: it disrupts the synthesis of the cell wall of the pathogen. When administered intramuscularly and intravenously, it provides a high concentration of the antibiotic in the body, significantly exceeding the MTC (0.01 μg / ml). It penetrates well through the blood-brain barrier both intravenously and intramuscularly (at a dose of at least 1.0) [6]. The effectiveness of ceftriaxone in the treatment of patients with early forms of syphilis is reflected in a number of publications [7-10]. It has been traced in most detail in relation to primary syphilis [7]. This study used Rocephin, an expensive Swiss drug that has earned a reputation as the most purified and counterfeit-proof. There are results of studying the concentration of ceftriaxone in the blood serum, in the cerebrospinal fluid, as well as in the tissues of the placenta and fetus (studies were carried out with other ceftriaxones – Lendacin and Megion) [11, 12]. Subsequently, ceftriaxones from various domestic manufacturers appeared, but they were not compared in terms of the effectiveness of therapy for syphilis both with each other and with foreign analogues. Long-term results of treatment have not been traced, especially with latent forms of syphilis. There are also no works on the effectiveness of ceftriaxone in late forms of syphilis.

However, despite the fact that the necessary studies have not been carried out, ceftriaxone is increasingly being used in the treatment of all forms of syphilis, including late ones. This is due to the following circumstances: firstly, the drug is convenient for outpatient treatment – 1 injection per day; secondly, the range of use of penicillin preparations is gradually but steadily narrowing for a number of reasons that have already been mentioned. Water-soluble penicillin is used less and less as patients avoid hospitalization; penicillin of “medium” duration (procaine-penicillin) has long been absent in Russia; Durant drugs have a mixed reputation because experience with 90s was not only positive, but also negative, and in addition, these drugs (Extencillin, Retarpen) have recently been supplied to the pharmacy network intermittently. However, since there were no evidence-based comparative studies of the effectiveness of ceftriaxone, it can hardly be considered reasonable to “crowd out” penicillin from medical practice. Therefore, a balanced approach to the use of ceftriaxone in syphilis is needed, and until the necessary studies are carried out, it should remain in the range of reserve drugs.

Among the reserve drugs there is a group of very rarely used – these are semi-synthetic penicillins ampicillin and oxacillin, which are similar in effectiveness to benzylpenicillin, but are better tolerated. This allows them to be used in most cases of allergy to benzylpenicillin. Undoubtedly, the main reason for their rare use is the same need for hospital treatment, since injections are made 4 times a day.

Finally, tableted reserve drugs – broad-spectrum antibiotics doxycycline, tetracycline, erythromycin – are rarely used today in specific therapy, which is primarily due to their significantly lower efficiency compared to benzylpenicillin. In the case of an allergy to penicillin, it can always be replaced with ceftriaxone or semi-synthetic penicillins. By the way, the opinion about the danger of cross-allergy to ceftriaxone seems to be somewhat exaggerated, such cases in our practice were literally isolated. As a rule, patients with an allergy to penicillin tolerated ceftriaxone without complications.

Conclusions

Over the past 20 years, there have been remarkable changes in the approaches and options for treating syphilitic infection. Significantly decreased the proportion of patients receiving water-soluble penicillin. In the 1990s and early 2000s, there was a significant increase in the proportion of patients treated with benzathine benzylpenicillin. There is reason to believe that this has led to an increase in cases of seroresistance. In the 90s, a drug of “medium” duration appeared in the practice of domestic syphilidologists – procaine-penicillin, which disappeared from the market in the next decade. This made it impossible to provide adequate outpatient treatment with penicillin preparations for patients with secondary and latent syphilis with a disease duration of more than 6 months, as well as late latent syphilis. Such patients, with a high probability of asymptomatic meningitis, received, as a rule, durant preparations of penicillin, which did not provide sanitation of the cerebrospinal fluid, which could later lead to the development of late manifest forms of syphilis. Since the mid-2000s, this problem has been eliminated with the increasing use of ceftriaxone in practice, which provided an outpatient treatment option that met the desires of both patients and doctors. Currently, one can observe the “crowding out” of penicillin preparations by ceftriaxone, without sufficient scientific justification for such a practice.

In this regard, it seems necessary: ​​

1. To return procaine-penicillin to the practice of antisyphilitic therapy, which will provide more opportunities for the treatment of those forms of syphilis in which this drug is indicated.
2. To conduct a comparative clinical study of the effectiveness of ceftriaxone preparations from different manufacturers in latent and late forms of syphilis.
3. Ensure the hospitalization of socially adapted patients with syphilis, if they have appropriate indications, in order to increase the use of water-soluble penicillin as a drug with optimal efficacy in the treatment of syphilitic infection.

Toxicoderma in the treatment of secondary syphilis: more questions than answers | Yakovlev A.B.

The syphilis epidemic of the 1990s, the subsequent increase in the number of complications resulting from the insufficient development of methods of treatment with prolonged penicillin preparations, the current state of monitoring the effectiveness of therapy for this socially significant disease are factors that determine the social significance of the problem today. Social conditions, conflicts and social explosions that are in constant negative dynamics do not contribute to improving the immune status of the population. Changing immunological reactivity leads to a change in the clinical manifestations of the syphilitic infection itself [1], worsening of the course of an already existing dermatosis against the background of a syphilitic infection [2] and, of course, to the occurrence of complications in the course of antibiotic therapy for syphilis. We are talking about allergic and toxic-allergic reactions that occur on the introduction of a treponemocidal antibiotic into the body.

Currently, there are no publications in the available medical literature in which the likelihood of toxic-allergic reactions during the treatment of syphilis would be clearly defined from the standpoint of evidence-based medicine. In addition, the recommendations contained in the Instructions for the treatment of syphilis, both in the 2000 edition and in the Methodological recommendations of 2013, do not stand up to criticism. penicillin drug to semi-synthetic (oxacillin). At the same time, the possibility of cross-reactions is not discussed, the question is not discussed: what will happen if the therapy of syphilis in a patient with an already developed toxic-allergic reaction to penicillin is continued [3, 4]?

Meanwhile, allergic and toxic-allergic reactions to antibiotics that occur during the treatment of STIs are by no means uncommon; they occur in the practice of a dermatovenereologist several times a year. Based on our observations, we estimate the total probability of occurrence of toxic-allergic reactions during the treatment of major STIs (syphilis, gonorrhea, chlamydia, trichomoniasis) at 5–7%. One of the studies of Chinese colleagues, which boasts a fairly large sample – 1125 patients (!) – indicates an almost 3% probability of intolerance to benzathine benzylpenicillin alone [5]. The number of officially registered anaphylactic reactions to penicillins during the treatment of syphilis does not exceed 0.4% [6].

In addition to the above, there are other issues related to the standards of therapy for toxicoderma. Indeed, in the event of severe toxicoderma, we, regrettably, will be forced to cancel specific treatment and prescribe therapy with detoxification and, most importantly, systemic corticosteroid drugs. And what will be the course of a syphilitic infection during the treatment of toxicoderma with corticosteroids? Won’t this lead to the emergence of seroresistance, and in the future – to neurosyphilis and other “charms” of late acquired syphilis? To date, our standards and guidelines do not provide answers to these questions. Only in the description of the preparation for the start of specific therapy in patients with progressive paralysis is there a mention of the use of prednisolone in order to prevent a violent Lukashevich–Jarish–Herxheimer reaction and exacerbation of psychotic symptoms [7].
These issues are not covered in serious scientific publications.

Here is our clinical observation, which in a certain way illustrates the urgency of the presented problem.

Patient Z., 38 years old, applied to the Dermatovenereological Dispensary with complaints of rashes on the lateral surfaces of the body for 10 days. The rash was accompanied by mild itching.
Disease history. The patient considers herself ill for 10 days, when rashes of “spots” began to appear on the lateral surfaces of the body. She did not immediately go to the doctor, she took clemastine on her own and, on the recommendation of a pharmacy employee, lubricated the rashes with a weak corticosteroid ointment. Later, the patient remembered that this was not the first episode of rashes, that similar rashes had occurred for about 1 month. back and were also accompanied by mild itching.
Life story. native Muscovite. I have not traveled abroad in the last 2 years. She is divorced and has a 15 year old son. Occupation: Software engineer.
Concomitant diseases: +2D hypermetropia, chronic gastritis, varicose veins of the lower leg, uterine fibroids, hemorrhoids, suffered from chicken pox in childhood.
Allergy anamnesis: during the introduction of complementary foods, there was diathesis, at the age of 16–18 years, rashes appeared after taking some pills for bronchitis.
Bad habits – denies.
Examination in the doctor’s office. The skin is pale, with a tendency to pigment neoplasms (common lentigo).
The musculoskeletal system is without features, beginning valgus deformity of the feet.
Lymph nodes are palpated occipital, axillary, inguinal.
Visible mucous membranes are without features, the conjunctiva of the eyes is slightly hyperemic. The mucous membranes of the mouth are pale pink in color. Zev is clean. The tonsils are slightly enlarged.
Respiratory organs – without features, vesicular breathing, no wheezing.
The heart sounds are clear, the rhythm is correct, 78/min. BP – 130/80 mm Hg. Art.
The abdomen is soft, painless, the stool is regular; there is a tendency to constipation.
Urination regular, painless.
Neurological status – without features, meningeal symptoms are absent. Consciousness is clear, contact is maintained.
Sexual history. Contacts with unfamiliar men denies. She reported that the last sexual intercourse took place 3 months. back, with a man whom the patient knows quite well.
local status. The skin process is widespread, symmetrical, localized mainly on the lateral surfaces of the body (Fig. 1), in the abdomen, and partially in the back, on the forearms and back of the hands (Fig. 2). Rashes are represented by small-spotted elements 3–4 mm in size, partially elevating, without a tendency to merge. The skin of the palms is intact. On the skin of the soles there are single papular rashes, covered with mild peeling (later regarded as “Biett’s collar”).
When viewed on a gynecological chair, a healed lesion was found in the region of the labia minora on the right, at “two o’clock”.

Research results
Complete blood count: hemoglobin – 120 g / l, erythrocytes – 3.9×1012 / l, leukocytes – 10×109 / l: stab – 4%, segmented – 54%, eosinophils – 4%, lymphocytes – 30%, monocytes – 8%; platelets – 260×109 / l, ESR – 5 mm / h.
General analysis of urine: clear, leukocytes – 3-4 in the field of view, squamous epithelium, 1-3 in the field of view, protein, bilirubin – not detected.
Blood biochemistry: total protein – 66 g / l, cholesterol – 5.9 mmol / l, ALT – 37 U / l, AST – 34 U / l, urea – 5.8 mmol / l, uric acid – 309 μmol / l , total bilirubin – 14.0 µmol/l, glucose – 5.0 mmol/l, C-reactive protein – 110 µg/l.
The results of serological studies: RMP 4+, titer 1:240. RPGA 4+, RIF – abs 4+, RIF200 4+. ELISA 4+.
Antibodies to HIV were not found.
Smears from the urethra (U), cervical canal (C), rectum (R): U – leukocytes – 5-6 in the field of view, gonococci, Trichomonas – not detected; С – leukocytes 5–6 in the field of view; R – leukocytes 1–2 in the field of view.
Consultation of the therapist: hypertension I-IIa degree, risk of the 2nd degree.
Neurologist’s consultation: dorsopathy, decreased peripheral reflexes on the left.
Ophthalmologist’s consultation: hypermetropia +2.5 D, astigmatism.
Based on the consideration of the anamnesis data (dynamics of sexual contacts), clinical manifestations (rashes on the lateral surfaces of the body, roseolous, remnants of a hard chancre in the area of ​​the right labia minora, papules of the soles) and the results of a serological study (positive serological reactions), the diagnosis was made: secondary manifest syphilis.
The patient was prescribed treatment with ceftriaxone (Rocefin) 1 g intramuscularly No. 20 in combination with oral chloropyramine tablets 25 mg 2 times a day. Appointments were made in accordance with the Methodological recommendations of the RODVK of 2003 [7].
The patient was issued a prescription by the attending physician indicating the international non-proprietary name of the antibiotic – ceftriaxone. The recommendation that Rocephin was needed for treatment was given orally, and later the patient either forgot about it or decided to save money and bought cheap ceftriaxone from another manufacturer, which, moreover, had the same drug name as the international non-proprietary name . As a result, during the first 7 days the patient was not treated with Rocephin. After the 2nd or 3rd antibiotic injection, the patient had an exacerbation reaction of Lukashevich-Yarish-Herxheimer in the form of an increase in the brightness of the existing rashes, swelling of the papules of the soles, the appearance of fresh rashes on the scalp (Fig. 3), on the skin of the chest, an increase in temperature to 38oC, malaise. The appearance of an exacerbation reaction clearly indicates that the antibiotic has had its effect.
However, after the 5th–6th injection, the patient began to develop intensely itchy papulo-vesicular rashes against the background of persisting specific rashes on the skin of the trunk and extremities. The greatest number of rashes was noted in the neck, forearms, and thighs. In the thenar region of the palms and the transverse arch of the soles, the eruption seemed to be accompanied by particularly intense itching, as the patient scratched them particularly hard, and weeping appeared.
The fact that the patient was not treated with Rocephin became clear by the 7th or 8th injection of ceftriaxone.
On the basis of newly appeared symptoms (itchy papular-vesicular rashes, scratching, weeping), as well as a negative analysis for scabies mites, the patient was diagnosed with toxicoderma, papular-vesicular form.

At the consultation with the head of the department, the attending physician and the consultant, it was decided to continue the specific treatment in full, adding to it the standard therapy for toxicoderma, and from the 9th day of treatment, the patient was prescribed the “native” Rocephin (with a conversation about the need for strict compliance with the prescription of the attending physician!). The patient categorically refused hospitalization.
The following drugs were prescribed for toxicoderma: dexamethasone solution 8 mg (2 ml) daily intramuscularly No. 5, then 6 mg (1.5 ml) No. 5, then 4 mg (1 ml) No. 5; Enterosgel in the form of a powder, 1 tablespoon 2 rubles / day for 12 days; antihistamines – chloropyramine, clemastine – the patient received as long as there was severe itching, after which she canceled them herself, despite the requirement of the attending physician to strictly follow the recommendations. Outwardly, for papular-vesicular rashes and oozing, drugs were prescribed: oxycort aerosol 2-3 rubles / day – the first 3 days, betamethasone HA cream, fukortsin for separate scratching. The need for such topical treatment persisted until approximately the 10th dexamethasone injection, after which the topical treatment was withdrawn, this time by the attending physician.
Thus, the patient received most of the course of ceftriaxone (Rocephin) “under cover” of dexamethasone administered intramuscularly, and another 4 days of dexamethasone injection continued after completion of the Rocephin injection.
The results of a clinical blood test on the 9th day of Rocefin injection: hemoglobin – 116 g / l, erythrocytes – 3.5×1012 / l, leukocytes – 5×109 / l: stab – 1%, segmented – 48%, erythrocytes – 9%, lymphocytes – 37%, monocytes – 5%, ESR – 15 mm/h.
In the general analysis of urine – no pathology.
A specific skin process was resolved quite quickly on the background of Rocephin. The manifestations of toxicoderma, which resembled eczema, resolved almost completely by the 12th injection of dexamethasone.
What was the subsequent dynamics of the microprecipitation reaction, according to which, according to the order of the Ministry of Health of the Russian Federation of 2006, we evaluate the effectiveness of the treatment of syphilis?
After 1 month after treatment, RMP 4+ remained, titer 1:8, after 2 months. after treatment – RMP 2+. In the same period, the patient suffered from acute pharyngitis and was treated with azithromycin 500 mg 1 r./day for 3 days in combination with other prescriptions from an ENT doctor.

After 6 months after treatment of RMP 1+ (weakly positive), there are no clinical manifestations of lues.
After 10 months after the treatment and resolution of toxicoderma, the patient suffered a traumatic extraction of the lower 6th tooth on the left, and the dentist prescribed the patient chloramphenicol 250 mg 4 times a day. However, on the 2nd day of taking the antibiotic, vesicular rashes reappeared, about which the patient again turned to a dermatologist. The rashes were completely similar to those that occurred during the treatment with ceftriaxone during the first 7 days of specific therapy: erythematous-squamous and papular-vesicular with predominant localization on the skin of the neck, forearms, hands, thighs, soles; rashes were accompanied by itching of moderate intensity. During this period, the patient underwent a general clinical blood test: leukocytes 8×109/l, stab – 7%, segmented – 46%, basophils – 1%, eosinophils – 9%, leukocytes – 30%, monocytes – 7%; ESR – 15 mm / h. RMP is negative.

Based on the clinical picture of the disease, a diagnosis of toxicoderma, papular-vesicular variant was made. Treatment was prescribed: suspension of betamethasone, 1 ml intramuscularly with an interval of 7 days No. 2 injections; solution of calcium gluconate 10%, 10 ml intramuscularly No. 7; ketotifen tablets 1 mg, 1 tablet 2 times a day, 20 days; external cream Lokoid.
The patient was advised to avoid penicillin antibiotics and chloramphenicol in the future.
RMP in the future, the patient remained persistently negative, and for syphilis she was removed from the dispensary record, but left on the account of a dermatologist due to the possibility of recurrence of episodes of toxic-allergic rashes.

What lessons do we learn by analyzing such clinical cases?
Firstly, in the course of careful history taking and study, even dubious and very approximate indications of past intolerance to certain nutrients or drugs should not be ignored, as was the case with our patient, who was able to remember that once in In early childhood, she developed rashes that appeared to resemble atopic dermatitis.
Secondly, the number of eosinophils in the peripheral blood, although it was formally within the normal range of 4%, was in the zone for which some authors propose to conduct clarifying studies. After all, the number of eosinophils at the level of 4–5% is a kind of border zone [8]. This, of course, does not mean that the normal values ​​​​should be reconsidered, but such a patient should still be treated with greater caution.
Thirdly, in patients predisposed to toxic-allergic reactions, specific treatment should be carried out with drugs that have a minimum elimination half-life from the body. In our case, for example, treatment was carried out with ceftriaxone, which maintains a bactericidal concentration within 20 hours and has a corresponding half-life of up to 24 hours. This is a fairly long period during which the sensitizing effect will persist. Apparently, it is preferable for such patients to be treated with water-soluble penicillin with injections up to 4 times a day in a hospital setting. And it is absolutely unacceptable to treat these patients with prolonged preparations such as benzathine benzylpenicillin-3 with injections of 2.4 million units 2 times a week. By the way, these relative contraindications have something in common with individual clinical manifestations of the secondary period of syphilis – diffuse alopecia and leukoderma. These symptoms are skin clinical markers of damage to the nervous system, ranging from minimal CSF pathology to meningovascular syphilis [9]. The intensity of antibiotic penetration through the blood-brain barrier depends on its “prolongation”: the more prolonged the antibiotic, the worse it penetrates the blood-brain barrier. It follows that it is preferable for allergic patients with secondary syphilis to prescribe non-prolonged penicillin preparations at once for two reasons.

Fourth, we face the psychological problem of the patient’s adherence to treatment. It is clear that every patient with any disease is interested in recovery. But the way to achieve this goal is different for different patients. Many would like to save money, buy a cheaper drug without informing the attending physician. Of course, in this case, the patient assumes a certain share of responsibility for the success or failure of the treatment and the occurrence of possible complications. But the psychological work with the patient still remains with the doctor. Sometimes it is enough just to remind the patient of the folk wisdom “What is expensive is sweet!”, And sometimes it is required, especially when trying to save money, longer mentoring work with the rationale for choosing a particular drug. In our case, we are not talking about the absence of antibacterial action in the generic drug ceftriaxone, but about the higher safety of Rocephin in an allergic patient [10].

Fifthly, the treatment of a patient with syphilis and with toxic allergic dermatosis arising from the treatment of syphilis should be carried out in accordance with the standards prescribed for the treatment of each of these diseases [7]. At the same time, one should take care of a sufficiently good compatibility of these methods in a particular patient. So, in our case, after the onset of a toxic allergic reaction, Rocephin injections were continued intramuscularly daily, and dexamethasone injections of 1-2 ml daily were added to them.

The sixth point of the analysis of our clinical case seems to follow from the previous one: why was the method of treatment of toxicoderma with dexamethasone tablets or intramuscular injections of a long-acting corticosteroid (betamethasone) not chosen? But the fact is that the immunosuppressive effect of oral dexamethasone preparations (tablets), as well as betamethasone crystalloid suspension, is too powerful for such a toxic-allergic process, which took place in our patient, and sufficient to cause an immunodeficiency state in a patient with syphilis. In such cases, the course of syphilis begins to resemble that in a patient with overt AIDS [11, 12]. At the beginning of our article, we already mentioned the lack of standards in predicting the dynamics of subsequent BC negativity after a full-fledged specific treatment for syphilis, but carried out against the background of systemic corticosteroid therapy for another inflammatory dermatosis. At the same time, there is evidence in the literature that the appointment of prednisolone before specific treatment contributes to a better tolerance of this treatment by patients with neurosyphilis, in whom the exacerbation reaction is highly undesirable: prednisolone “extinguishes” the manifestations of this reaction [13]. In this regard, we chose the therapy of toxicoderma with a rapidly excreted drug dexamethasone from the body – an aqueous solution for injection. And we weren’t wrong! Negative BC in our patient went according to the usual scenario, without the formation of an immunodeficiency state.

We will devote the seventh point of the analysis to assessing the effectiveness of preventing allergic reactions by prescribing a first-generation antihistamine antibiotic (chloropyramine) before the first injection. It is known that not only histamine is involved in the formation of an allergic reaction, but also circulating immune complexes, pro-inflammatory cytokines, neurotransmitters, and substance P [14]. It seems to us more rational to use drugs for the prevention of allergic, toxic-allergic and pseudo-allergic reactions, usually combined under the general name “mast cell membrane stabilizers”. These drugs usually include ketotifen, cetirizine, and fexofenadine. Of these drugs, the most “ancient” ketotifen has a certain disadvantage, the action of which develops slowly, gradually. For the prevention of allergic dermatosis, all three drugs can be given to the patient throughout the course of specific therapy, usually 20–28 days. Ketotifen is administered orally at 1 mg 2 times a day after meals. Cetirizine has its effect faster than ketotifen, it can be prescribed 1 r./day, 10 mg orally. Fexofenadine is administered orally at 120-180 mg 1 r./day or 60 mg 2 r./day. In addition, cetirizine and fexofenadine rarely cause severe drowsiness, which also increases their compliance.

The eighth point concerns one of the most important questions a venereologist will ever face: the problem of differential diagnosis of allergic and syphilitic eruptions. In the usual version, we are talking about establishing a diagnosis, for example, toxicoderma or syphilis. In such cases, serological tests help us [15]. But in our case, we are talking about establishing not a primary diagnosis, but a concomitant disease. This disease is toxicoderma, which arose during the treatment of syphilis with an antibiotic. Specific reactions will not help us here. In such cases, the basis of differential diagnosis is the analysis of clinical manifestations. Extremely rarely, a syphilitic rash is vesicular, polymorphic (vesicles and papules), itchy. The last point is especially important, because allergic vesicular rash itches so intensely that the intensity of this itching can be elevated to the rank of a distinctive symptom. The medical literature describes cases of itching in a patient with syphilis, but the intensity of this itching cannot be compared with the extremely intense itching in allergic dermatosis. Itching of the skin in a patient with syphilis may also occur not due to manifest rashes, but against the background of damage to internal organs, for example, with toxic hepatitis [16].

The next differential diagnostic feature is the morphology of the lesions. In typical eczema-like rashes in the acute period of the rash, vesicles are often located on the extremities, especially along the edge of the fingers and toes, palms, in the thenar or hypothenar region. Differential diagnosis of syphilitic and allergic rashes can be difficult due to the Lukashevich–Jarish–Herzheimer exacerbation reaction [9]. The latter is characterized by the symptom of “flare-up of the rash”, most pronounced in roseolous syphilis. There is an opinion, and not without reason, that the Lukashevich-Yarish-Herxheimer reaction itself is a toxic-allergic process, in which, however, eruptive elements contain a large number of pale treponemas [12, 17].

In our case, the patient was “lucky” and the toxic-allergic eczematous reaction to ceftriaxone was represented by eczema-like papular-vesicular rashes, which made it possible to easily distinguish these rashes from those during an exacerbation reaction. Such a course of toxidermia when taking cephalosporins is less common than maculopapular or measles-like rashes. Cross-reactions to penicillins and cephalosporins are explained by the fact that cephalosporins have a six-membered dihydrothiazine ring in their molecule, and penicillins contain a five-membered β-lactam thiazolidine ring [18]. These rings are the cause of cross-reactions in 5-6% of cases. Nevertheless, the relatively low percentage of cross-reactions between penicillins and cephalosporins is explained by significant differences in the structure of side chains in the molecules of these antibiotics [18].

Much greater difficulty arises when a patient who has just begun treatment for syphilis against the background of an exacerbation reaction develops erythematous-squamous spotted rashes caused, for example, by food allergens. We observed such a case when a patient who had just begun treatment for syphilis drank red wine, which caused spotted erythematous toxicoderma. In such cases, attention should be paid to the symptom of “fusion”: with a small amount, toxidermic rashes tend to merge, and syphilitic ones will show such a tendency only in exceptional cases of the extreme prevalence of a specific process (drain roseola).

Thus, analyzes of clinical cases similar to the one we have just described can be very instructive when viewed from different positions and points of view and are of interest not only to venereologists, but also to dermatologists, allergists, immunologists, health care organizers. These clinical reviews show that all kinds of guidelines, treatment regimens and formularies are not once and for all established legislative acts, but are dynamically developing, constantly updated and supplemented by the quintessence of our knowledge.

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