Dental Antibiotic Lecture with Voice PDF

Antibiotic therapy Vaccines for healthcare worker Written by: Mohammad Abushehab Corrected by: Yazeed Al-jammal  Key points ⚫ Introduction ⚫ Choice of the proper antibiotic ⚫ Antimicrobial combinations ⚫ Choice of the route and efficacy assessment Sir A. Fleming: discoverer of P...

Antibiotic therapy Vaccines for healthcare worker Written by: Mohammad Abushehab Corrected by: Yazeed Al-jammal  Key points ⚫ Introduction ⚫ Choice of the proper antibiotic ⚫ Antimicrobial combinations ⚫ Choice of the route and efficacy assessment Sir A. Fleming: discoverer of Penicillin Antibiotics began with Sir Alexander Fleming, who was awarded the Nobel Prize in 1945 for his discovery of penicillin. Before penicillin, sulfa antibiotics were used, but they had numerous adverse effects, limiting their success. Antibiotics have been widely used since the 1940s.  Antibiotics ⚫ Penicillins ⚫ Cephalosporins ⚫ Carbapenem ⚫ Monobactams ⚫ Glycopeptide ⚫ Aminoglycoside ⚫ Fluroquinolone  Penicillins ⚫ Penicillin G ⚫ Penicillin V ⚫ Amoxicillin ⚫ Cloxacillin ⚫ Oxacillin ⚫ Ampicillin ⚫ Piperacillin ⚫ Methicillin  Choice of the proper agent 1) Identification of the organism 2) Antimicrobial susceptibility 3) The narrowest effective spectrum 4) Host factors include allergies, age, renal and liver function, the site of infection, pregnancy, and metabolic disorders, particularly diabetes. Identification of the organism Gram Stain and Culturing ELISA/Lattex Agglutination: PCR (Polymerase Chain (Best Method): Some bacteria may not grow in Reaction): Start with a biopsy, which can cultures, so we use ELISA or Molecular tests like PCR be taken from sources like latex agglutination to detect are particularly useful CSF, pleural fluid, synovial antibodies or perform serology. when it's difficult to fluid, peritoneal fluid, urine, For example, in HIV, we look culture the infecting or sputum. After obtaining the for HIV antibodies, or we may microorganism (e.g., for sample, apply a Gram stain look for antibodies to Brucella. detecting COVID-19). and proceed with culturing to Bacteriologic Statistics: identify the organism. This involves understanding the organisms most likely to cause infection in a specific clinical setting. This information is drawn from research studies. For example, community-acquired pneumonia is most Culture (Ideal for Bacteria): commonly caused by viruses, followed by bacteria like Culture is the best method for Streptococcus pneumoniae. In such cases, it may not be identifying bacterial infections. It's ideal necessary to know the specific organism, as statistical to collect cultures before starting probabilities are often sufficient. antibiotics. However, this does not mean Cellulitis is an infection that is challenging to study, and that culturing is impossible after the biopsy cultures of cellulitis often fail to identify the patient has started antibiotics. Cultures causative microorganism (95% of the time). However, based on research, we know that 90% of cellulitis cases for viruses are also available, though in healthy individuals are caused by Staphylococcus they are not commercially widespread. aureus or Group A Streptococcus. Antimicrobial susceptibility You should be aware of which antibiotics are effective against each microorganism and which ones the microorganism is resistant to. As we know, we are currently in an era of antimicrobial resistance, and most of the oral flora are resistant to penicillin. Therefore, antimicrobial susceptibility can be determined by: ⚫ Disk diffusion method One common method used to test antimicrobial susceptibility is the disk diffusion test, which is employed by many laboratories. In this test, bacteria are spread on a plate, and antibiotic-impregnated disks are placed on the. surface. The diameter of the inhibition zone is measured to determine the effectiveness of the antibiotic. There are established standards that define whether bacteria are considered resistant or susceptible based on the size of the inhibition zone. ⚫ Epsilometer (E-test) ( In this method, bacteria are spread on a plate, and a strip with a gradient of antibiotic concentrations (from low to high) is placed on the surface. The zone of inhibition where the strip intersects with the bacteria indicates the Minimum Inhibitory Concentration (MIC) of the antibiotic for that particular bacterium.) ⚫ Minimum inhibitory conc. (MIC) is determined by applying different concentrations of an antibiotic to separate bacterial plates and measuring the effect. However, this test is rarely used today, as the E-test has largely replaced it)  Antimicrobial susceptibility ⚫ Minimum bactercidal conc. (MBC) ⚫ Specialized testing is required for fastidious organisms, such as obligate anaerobes, Haemophilus species, pneumococci, and MRSA. Fastidious organisms are difficult to grow under standard laboratory conditions, so reliance on specific diagnostic tests or specialized research is necessary for accurate identification. ⚫ Resistance mechanism of the bacteria: ⚫ eg: Staph. aureus, E. coli, Enterbacter …..  Pharmacodynamic profile ⚫ Area under the curve / time curve to MIC (AUC / MIC) (The goal is to achieve a sufficiently high Area Under the Curve (AUC) relative to the Minimum Inhibitory Concentration (MIC) to ensure effective bacterial killing) ⚫ Maximal serum conc. / MIC (C max / MIC) (It reflects the relationship between the peak concentration of the drug in the blood and the MIC, which influences the effectiveness of the antibiotic) ⚫ Time during dosing interval that plasma conc. exceed the MIC (t / MIC) (The longer the drug concentration stays above the MIC, the more effective the treatment will be)  Conc. & Time dependent dosing ⚫ Antibiotics work in two ways: 1. Concentration-dependent (e.g., fluoroquinolones, aminoglycosides like gentamicin): As the concentration increases, the rate of bacterial death accelerates. This typically requires larger doses at longer intervals. 2. Time-dependent (e.g., beta-lactams, vancomycin): The reduction in bacterial density is proportional to the time the drug concentration remains above the MIC. This requires sufficient dosing at appropriate intervals to maintain the concentration above the MIC.  In the graph, the dashed lines represent the MIC for different microorganisms. Organism A The area above the dashed lines, up to the curve, indicates the Concentration time the concentration remains above the MIC. For the second dose, the time to reach the MIC is longer than for the first dose. Time Organism B Organism C A : resistant; B : moderately susceptible; C very susceptible  The dashed line shows the behavior of the drug on the bacteria. Organism A The larger the curve above the line, the further the maximum, and the longer the Concentration time between doses, the more effective the antibiotic is at killing the bacteria. This is why the graph shows the effect of the antibiotic on multiple organisms. If the value is below the line, it indicates that the antibiotic is the best choice for that bacterium. If it's in the middle, the Time antibiotic is acceptable. Organism B Organism C If it's above the line, it means the drug is not working well against that bacterium and it is resisting the treatment A : resistant; B : moderately susceptible; C very susceptible ‫‪To understand the concept clearly and correctly:‬‬ ‫الخط المنقط يُظهر سلوك‬ ‫الدواء تجاه البكتيريا‪.‬كلما كان‬ ‫‪Organism A‬‬ ‫المنحنى الذي فوق الخط أكبر‪،‬‬ ‫وكان الحد األقصى أبعد‪ ،‬وكان‬ ‫الوقت بين الجرعتين أطول‪،‬‬ ‫‪Concentration‬‬ ‫كان المضاد الحيوي أكثر فعالية‬ ‫في قتل البكتيريا‪.‬لذلك‪ ،‬في‬ ‫الشكل يظهر تأثير المضاد‬ ‫الحيوي على عدة كائنات دقيقة‪.‬‬ ‫إذا كان المربع أسفل الخط‪،‬‬ ‫فهذا يعني أن المضاد هو‬ ‫األفضل لقتل هذه البكتيريا‪.‬إذا‬ ‫كان في الوسط‪ ،‬فالمضاد‬ ‫‪Time‬‬ ‫مقبول‪.‬أما إذا كان فوق الخط‪،‬‬ ‫‪Organism B‬‬ ‫‪Organism C‬‬ ‫فهذا يشير إلى أن الدواء ال‬ ‫يعمل بشكل جيد ضد هذه‬ ‫البكتيريا وأنها تقاومه‪.‬‬ Initial Population: The green circles represent a bacterial population, Resistance selection with some bacteria already carrying resistance to "Antibiotic X" (marked with a red horizontal bar). Exposure to Antibiotic: When "Antibiotic X" is introduced, it begins to kill bacteria that are susceptible (those without the resistance marker). Resistant Bacteria Survive: Over time, as days pass and the antibiotic continues to be used, the susceptible bacteria are eliminated, while the resistant bacteria survive and reproduce. Resulting Population: Eventually, the bacterial population becomes predominantly (or days entirely) resistant, rendering "Antibiotic X" ineffective. Antibiotic X Antibiotic X  Published data There are various applications that provide information on the appropriate dose, drug of choice, and potential drug-drug interactions for any infection or disease. ⚫ Manuals, such as Sanford’s and the Medical Letter on Drugs and Therapeutics, provide valuable information on drug dosing, choice, and interactions. (Note: Use this information within its proper context.  Host factors Previous History of Adverse Reactions: Includes allergies or adverse effects directly caused by the drug (e.g., nausea or gastrointestinal upset, which are not considered allergic reactions). Neutrophil Function: Neutropenia (a reduced number of neutrophils in the blood) is commonly seen in cancer patients undergoing chemotherapy. These patients require aggressive treatment, as neutropenia is one of the most common causes of immunodeficiency. Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM), and Asplenia: Patients with these conditions are typically treated empirically. Three Types of Antibiotic Prescriptions Therapeutic: The causative microorganism (M.O) is identified, and treatment is specifically targeted: A: Resistant B: Moderately Susceptible Empirical: The specific causative microorganism is unknown, but based on clinical knowledge, the most likely bacteria are targeted with antibiotics. Prophylactic: Antibiotics are given to patients with known immune deficiencies to prevent infection. For example: In AIDS patients, when their CD4+ count drops below 200, they are at high risk of developing pneumonia. In such cases, they are given the antibiotic Bactrim.  Age ⚫ Renal function (impaired physiologic function) (decreases with age) ⚫ Absorption ⚫ Tetracyclines (Not recommended for children under 8 years old) ⚫ INH (Isoniazid), a medication for tuberculosis (TB), carries a risk of hepatotoxicity, with the risk increasing significantly after the age of 30. ⚫ Nephrotoxicity is increased in elderly patients and those with kidney disease. ⚫ Aminoglycosides (Ag) are associated with cochlear toxicity, which can lead to hearing loss or deafness.  Genetic / metabolic Patients with G6PD Deficiency: Should avoid sulfa drugs or (another unspecified drug), as they may cause hemolysis. Diabetes Mellitus (DM): -Sulfa drugs can potentiate the effects of sulfonylurea hypoglycemic agents, increasing the risk of hypoglycemia. -Dextrose load can cause an increase in glucose levels. -Poor intramuscular (IM) absorption may occur due to microangiopathy, so the intravenous (IV) route is preferred. Pregnancy ⚫ Safe: Penicillin (PCN), cephalosporins, erythromycin base. ⚫ Dangerous: Tetracyclines (risk of hepatic toxicity and dental discoloration). ⚫ Teratogenic: Metronidazole was previously classified as Category C but is now in Category B, meaning it can be prescribed if the benefits outweigh the risks. ⚫ Contraindicated: Fluoroquinolones (FQ), clarithromycin, erythromycin. ⚫ To Be Avoided (Even if Considered Safe): Rifampin, aminoglycosides (Ag), azithromycin, clindamycin, imipenem, vancomycin, trimethoprim (TMP). ⚫ Abx dose needs to be increased? Yes, some antibiotics need dose adjustments in pregnancy due to increased blood volume, renal clearance, and altered metabolism. For example, penicillins and cephalosporins may require higher doses, while others like macrolides usually do not  Renal and liver fx ⚫ Vancomycin and aminoglycosides (gentamicin, amikacin) can be given, but renal function should be closely monitored.  Site of infection Some antibiotics may not be effective at certain sites of infection, so it is important to consider the site when prescribing treatment. ⚫ Optimal therapy requires maintaining a concentration above the MIC at the site of infection. This is particularly important for conditions such as meningitis, endocarditis, osteomyelitis, chronic prostatitis, intraocular infections, abscesses, foreign bodies, and urinary tract infections (UTIs).  Immune system ⚫ Abx can cause immune suppression esp. in the immunosuppressed patients. ⚫ Suppress monocyte transformation, phagocytosis, chemotaxis, antibody production.  Combinations ⚫ Some clinicians believe that using combinations of antibiotics is beneficial, but the issues of antagonism and increased toxicity must be considered. While some physicians use combinations for a sense of security (to cover a wider range of pathogens), this approach may lead to deleterious effects, where the harmful consequences potentially outweigh the perceived benefits.  Indications for Combination Therapy: Prevention of Emergence of Resistant Bacteria: For example, tuberculosis (TB) and Staphylococcal endocarditis. Polymicrobial Infections: Such as abdominal sepsis. Initial Therapy: For example, combining aminoglycosides (Ag) with piperacillin. Synergism: When two antibiotics work together to enhance effectiveness. Synergism for Resistant Organisms: ⚫ There is limited data to support the benefit of combination therapy, but examples include: Penicillin (PCN) + Aminoglycosides (Ag) → Enterococcal endocarditis Oxacillin + Aminoglycosides → Staphylococcal endocarditis Anti-pseudomonal β-lactam + Aminoglycosides → Pseudomonas bacteremia ⚫ These combinations are particularly useful in patients with an impaired immune system.  Antagonism ⚫ Although there are many in vivo reports, only a few combinations have shown antagonism. Clinically, antagonism has been observed with penicillin (PCN) and tetracycline. Combining two beta-lactams can induce beta-lactamases. This is especially important in immunosuppressed patients.  Adverse effects ⚫ 5% of pts will have a side effect. ⚫ Combinations → more cost, more adverse effects.  Anaphylaxis ⚫ Anaphylaxis from Beta-Lactams: Beta-lactams are the most common antibiotics to cause anaphylaxis. Penicillin (PCN) carries a 0.01% risk of anaphylaxis, with death occurring in 1 out of 100,000 courses. 10-20% of patients visiting your clinic may claim to have an allergy to PCN, but only 50% of those will actually have a positive reaction to a skin test. This is consistent with information from both the slides and online sources.  Anaphylaxis ⚫ Cross-Reactions and Allergic Reactions: PCN can cross-react with cephalosporins, especially class 1. Some individuals may have allergic reactions to both. There is a very small chance of cross-reaction with carbapenems (~1%). There is no cross-reaction with aztreonam, except for ceftazidime. Although aztreonam has a beta-lactam ring, it is a monobactam, and its structure differs from that of PCN. ⚫ Considerations for Prescribing: Beta-lactams are more expensive and tend to have more side effects.  Route ⚫ Oral → stable , mild infection (reliable pts) ⚫ IV → serious infections (sepsis) + DM  Monitoring the response ⚫ After administering the antibiotic, it is important to monitor the patient's response from several aspects: Clinically: Assess whether the patient’s condition has improved or worsened. Drug Levels: For example, monitoring vancomycin levels. Lab Tests: Include checking white blood cell (WBC) count, liver enzymes, and kidney function tests.  Cost ⚫ If all other factors are equal, the least expensive drug should be chosen  Needle stick ⚫ Before discussing vaccines, let’s remember that needlestick injuries are common in the medical field and carry the following risks of transmission: Hepatitis B virus: 30% Hepatitis C virus: 3% HIV: 0.3%  HBV Vaccine recommendations ⚫ The HBV vaccine should be offered to all healthcare workers. It has been required in the USA since 1991, raising some human rights concerns (e.g., what if someone refuses? cough Awen Halasa cough). You are not required to accept the vaccine; you can decline it and sign a declination form. While your establishment can decide whether to mandate the vaccine, most healthcare facilities do not. If you are exposed to HBV or change your mind, you can still receive the vaccine later. Your employer may not offer you the vaccine if: you are already vaccinated, have antibodies, or if the vaccine is contraindicated in your case.  vaccine HBV vaccine The vaccine contains the HBV surface antigen and cannot transmit the virus. The vaccination course consists of 3 shots: at 0, 1, and 6 months. This series is administered once, and there is no need to repeat it after several years. One of the few indications for repeating the course is during an outbreak, in which case a booster shot may be given. If you are exposed to HBV, immediate vaccination is crucial (if you were not previously vaccinated or do not have documentation of your antibody titer). You can also receive HBV immunoglobulin in case of exposure.  vaccine HBV vaccine (cont) ⚫ You do not need to accept the vaccine ⚫ You can decline it and sign a declination form ⚫ If you are exposed to HBV or changed your mind, you can still receive it ⚫ Your employer might not offer you the vaccine if: – You are vaccinated – Have Antibodies – Contraindicated in your case Responder vs Non-Responder: One month after the final dose, check antibody titers for response: >10 IU/L = Responder 10 IU/L), you are fully protected for up to 20 years. Hepatitis B Importance of Vaccination: This is an image of an HBV patient with severe ascites. HBV is a serious disease, and vaccination should be taken seriously. After vaccination, it’s essential to confirm your response (antibody titer >10), especially for healthcare workers, as they are at high risk. Non-Responders: If your antibody titer is 10, you are a responder. If the titer is