Presentation is loading. Please wait.

Presentation is loading. Please wait.

DRUG THERAPY OF INFECTIOUS DISEASES. Classification of infectious diseases  According to onset and duration  According to location  According to item.

Similar presentations


Presentation on theme: "DRUG THERAPY OF INFECTIOUS DISEASES. Classification of infectious diseases  According to onset and duration  According to location  According to item."— Presentation transcript:

1 DRUG THERAPY OF INFECTIOUS DISEASES

2 Classification of infectious diseases  According to onset and duration  According to location  According to item present  According to sequence of appearance  According to epidemiological factors

3 Classifications according to onset and duration  Acute disease -- Rapid onset and short duration. E.g. common cold, measles  Chronic disease -- Slower onset and longer duration. eg TB, leprosy  Subchronic disease -- ermediate to acute and chronic both in onset and duration. eg gingivitis  Latent disease -- One characterized by periods of activity erspersed with periods of inactivity. E.g.: malaria, herpes simplex.

4 Classification according to location  Local infection -- Confined to a specific area of the body. E.g.: cystitis, vaginitis, myocarditis.  Focal infection -- Infection that started in one place and later on spread to other areas. E.g. tuberculosis, sinus infection, infected tooth.  Systemic (generalized) infection - Occurring throughout the body

5 Classifications according to item present  Septicemia -- A microbe is present in the blood, is continuously being delivered from tissues to blood and is actively multiplying in the blood. Typical of systemic diseases. Often fatal.  Bacteremia -- Presence of bacteria in the blood  Viremia -- Presence of virus in the blood of the body  Pyemia -- Poisoning of the blood by pus-producing bacteria released from an abscess  Toxaemia -- Presence of bacterial toxins in the blood. Can result in fever, diarrhea and vomiting.

6 Classification according to sequence of appearance  Primary infection - Initial infection in a healthy person  Secondary infection - Occurs after primary infection  Superinfection - A secondary infection due to the destruction of the protective normal flora of the body by the use of a broad spectrum antibiotic Also defined as a secondary infection facilitated by a primary infection e.g. HIV and AIDS

7 Epidemiological factors - mode of appearance, number of cases, trends of diseases in populations Classifications according to epidemiological factors  Endemic disease (endemia) - Present regularly in particular area of the world, and total number and severity are low  Ecdemic disease (ecdemia) - A foreign disease brought to a new area by travelers or immigrants from a foreign country  Pandemic disease (pandemia) - A disease that affects many people and which occurs across neighboring cities, countries or continents. Affects many people.  Epidemic disease (epidemia) - Appears suddenly, affects many people and is confined to a particular, often the same, area. Morbidity rate and mortality rate above what is normal.  Sporadic disease (epidemia) - Appears suddenly, in a random and unpre- dictable manner, affects only a few people, and limited to a few, usually unrelated, places.  Outbreak - Few cases, often related in time and location, and sharing same manifestations

8 Threat of emerging infectious diseases Due to constant changes in our lifestyles and environments, there are constantly new diseases that people are susceptible to, making protection from the threat of infectious disease urgent. Many new contagious diseases have been identified in the past 30 years, such as AIDS, Ebola, and hantavirus. Increased travel between continents makes the worldwide spread of disease a bigger concern than it once was. Additionally, many common infectious diseases have become resistant to known treatments.

9 Problems of antibiotic resistance Because of the overuse of antibiotics, many bacteria have developed a resistance to common antibiotics. This means that newer antibiotics must continually be developed in order to treat an infection. However, further resistance seems to come about almost simultaneously. This indicates to many scientists that it might become more and more difficult to treat infectious diseases. The use of antibiotics outside of medicine also contributes to increased antibiotic resistance. One example of this is the use of antibiotics in animal husbandry. These negative trends can only be reversed by establishing a more rational use of antibiotics through treatment guidelines.

10 Beta-Lactam Antibiotics

11 A penicillin culture

12 Cephalosporins and cephamycins are similar to penicillins chemically, in mechanism of action, and in toxicity. Cephalosporins are more stable than penicillins to many bacterial -lactamases and therefore usually have a broader spectrum of activity. Cephalosporins are not active against enterococci and Listeria monocytogenes.

13  These are drugs with a monocyclic -lactam ring. They are relatively resistant to lactamases and active against gram- negative rods (including pseudomonas and serratia). They have no activity against gram-positive bacteria or anaerobes. Aztreonam is the only monobactam available in the USA. It resembles aminoglycosides in its spectrum of activity. Aztreonam is given intravenously every 8 hours in a dose of 1– 2 g, providing peak serum levels of 100 g/mL. The half-life is 1–2 hours and is greatly prolonged in renal failure.  Penicillin-allergic patients tolerate aztreonam without reaction. Occasional skin rashes and elevations of serum aminotransferases occur during administration of aztreonam, but major toxicity has not yet been reported. The clinical usefulness of aztreonam has not been fully defined.

14  These substances resemble beta-lactam molecules but themselves have very weak antibacterial action. They are potent inhibitors of many but not all bacterial lactamases and can protect hydrolyzable penicillins from inactivation by these enzymes. Beta -Lactamase inhibitors are most active against Ambler class A lactamases (plasmid-encoded transposable element [TEM] - lactamases in particular) such as those produced by staphylococci, H influenzae, N gonorrhoeae,  salmonella, shigella, E coli, and K pneumoniae. They are not good inhibitors of class C -lactamases, which typically are chromosomally encoded and inducible, produced by enterobacter, citrobacter, serratia, and pseudomonas, but they do inhibit chromosomal lactamases of legionella, bacteroides, and branhamella.

15  The indications for penicillin- -lactamase inhibitor combinations are empirical therapy for infections caused by a wide range of potential pathogens in both immunocompromised and immunocompetent patients and treatment of mixed aerobic and anaerobic infections, such as intraabdominal infections. Doses are the same as those used for the single agents except that the recommended dosage of piperacillin in the piperacillin- tazobactam combination is 3 g every 6 hours. This is less than the recommended 3–4 g every 4–6 hours for piperacillin alone, raising concerns about the use of the combination for treatment of suspected pseudomonal infection.  Adjustments for renal insufficiency are made based on the penicillin component.

16 The carbapenems are structurally related to beta-lactam antibiotics. Ertapenem, imipenem, and meropenem are licensed for use in the USA. Imipenem has a wide spectrum with good activity against many gram- negative rods, including Pseudomonas aeruginosa, gram-positive organisms, and anaerobes. It is resistant to most lactamases but not metallo- lactamases. Enterococcus faecium, methicillin-resistant strains of staphylococci, Clostridium difficile, Burkholderia cepacia, and Stenotrophomonas maltophilia are resistant. Imipenem is inactivated by dehydropeptidases in renal tubules, resulting in low urinary concentrations. Consequently, it is administered together with an inhibitor of renal dehydropeptidase, cilastatin, for clinical use. Meropenem is similar to imipenem but has slightly greater activity against gram-negative aerobes and slightly less activity against gram- positives. It is not significantly degraded by renal dehydropeptidase and does not require an inhibitor. Ertapenem is less active than meropenem or imipenem against Pseudomonas aeruginosa and acinetobacter species. It is not degraded by renal dehydropeptidase.

17 The usual dose of imipenem is 0.25–0.5 g given intravenously every 6– 8 hours (half-life 1 hour). The usual adult dose of meropenem is 1 g intravenously every 8 hours. Ertapenem has the longest half-life (4 hours) and is administered as a once-daily dose of 1 g intravenously or intramuscularly. Intramuscular ertapenem is irritating, and for that reason the drug is formulated with 1% lidocaine for administration by this route. A carbapenem is indicated for infections caused by susceptible organisms that are resistant to other available drugs and for treatment of mixed aerobic and anaerobic infections. Carbapenems are active against many highly penicillin-resistant strains of pneumococci. A carbapenem is the beta- lactam antibiotic of choice for treatment of enterobacter infections, since it is resistant to destruction by the lactamase produced by these organisms. Strains of Pseudomonas aeruginosa may rapidly develop resistance to imipenem or meropenem, so simultaneous use of an aminoglycoside is recommended for infections caused by those organisms. Ertapenem is insufficiently active against P aeruginosa and should not be used to treat infections caused by that organism. Imipenem or meropenem with or without an aminoglycoside may be effective treatment for febrile neutropenic patients.

18 Chloramphenicol is a potent inhibitor of microbial protein synthesis. It binds reversibly to the 50S subunit of the bacterial ribosome. Because of potential toxicity, bacterial resistance, and the availability of other effective drugs (eg, cephalosporins), chloramphenicol is all but obsolete as a systemic drug. It may be considered for treatment of serious rickettsial infections, such as typhus or Rocky Mountain spotted fever, in children for whom tetracyclines are contraindicated, ie, those under 8 years of age. It is an alternative to a -lactam antibiotic for treatment of meningococcal meningitis occurring in patients who have major hypersensitivity reactions to penicillin or bacterial meningitis caused by penicillinresistant strains of neumococci. The dosage is 50–100 mg/kg/d in four divided doses.

19 Chloramphenicol is occasionally used topically in the treatment of eye infections because of its wide antibacterial spectrum and its penetration of ocular tissues and the aqueous humor. It is ineffective for chlamydial infections.

20 Newborn infants lack an effective glucuronic acid conjugation mechanism for the degradation and detoxification of chloramphenicol. Consequently, when infants are given dosages above 50 mg/kg/d, the drug may accumulate, resulting in the gray baby syndrome, with vomiting, flaccidity, hypothermia, gray color, shock, and collapse. To avoid this toxic effect, chloramphenicol should be used with caution in infants and the dosage limited to 50 mg/kg/d or less (during the first week of life) in full-term infants and 25 mg/kg/d in remature infants.

21 Tetracyclines are broad-spectrum bacteriostatic antibiotics that inhibit protein synthesis. They are active against many gram- positive and gram-negative bacteria, including anaerobes, rickettsiae, chlamydiae, mycoplasmas, and L forms; and against some protozoa, eg, amebas. The antibacterial activities of most tetracyclines are similar except that tetracycline- resistant strains may remain susceptible to doxycycline or minocycline, drugs that are less rapidly transported by the pump that is responsible for resistance

22 A tetracycline is the drug of choice in infections with Mycoplasma pneumoniae, chlamydiae, rickettsiae, and some spirochetes. They are used in combination regimens to treat gastric and duodenal ulcer disease caused by Helicobacter pylori. In cholera, tetracyclines rapidly stop the shedding of vibrios, but tetracycline resistance has appeared during epidemics. Tetracyclines remain effective in most chlamydial infections, including sexually transmitted diseases. Tetracyclines are no longer recommended for treatment of gonococcal disease because of resistance. A tetracycline—usually in combination with an aminoglycoside—is indicated for plague, tularemia, and brucellosis. Tetracyclines are sometimes employed in the treatment of protozoal infections, eg, those due to Entamoeba histolytica or Plasmodium falciparum. Other uses include treatment of acne, exacerbations of bronchitis, community-acquired pneumonia, Lyme disease, relapsing fever, leptospirosis, and some nontuberculous mycobacterial infections (eg, Mycobacterium marinum). Tetracyclines formerly were used for a variety of common infections, including bacterial gastroenteritis, pneumonia (other than mycoplasmal or chlamydial pneumonia), and urinary tract infections. However, many strains of bacteria causing these infections now are resistant, and other agents have largely supplanted Tetracyclines.

23 Erythromycin Clarithromycin (is derived from erythromycin) Azithromycin (differs from erythromycin and clarithromycin mainly in pharmacokinetic properties). The drug is slowly released from tissues (tissue half-life of 2–4 days) to produce an elimination half-life approaching 3 days. These unique properties permit once-daily dosing and shortening of the duration of treatment in many cases. For example, a single 1 g dose of azithromycin is as effective as a 7-day course of doxycycline for chlamydial cervicitis and urethritis. Community-acquired pneumonia can be treated with zithromycin given as a 500 mg loading dose, followed by a 250 mg single daily dose for the next 4 days. Ketolides (Telithromycin)

24 Aminoglycosides Streptomycin, neomycin, kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin The pharmacodynamic properties of aminoglycosides are: Concentration-dependent killing Significant post-antibiotic effect Aminoglycosides eliminate bacteria quickest when their concentration is appreciably above the MIC for an organism, this is referred to as concentration dependent activity. The aminoglycosides also exhibit a significant post-antibiotic effect (PAE). PAE is the persistent suppression of bacterial growth following antibiotic exposure. Practically speaking this means that trough levels can drop below the MIC of targeted bacteria for a sustained period without decreasing efficacy.

25 Sulfonamides are infrequently used as single agents. Formerly drugs of choice for infections such as Pneumocystis jiroveci (formerly P carinii) pneumonia, toxoplasmosis, nocardiosis, and occasionally other bacterial infections, they have been largely supplanted by the fixed drug combination of trimethoprim-sulfamethoxazole. Many strains of formerly susceptible species, including meningococci, pneumococci, streptococci, staphylococci, and gonococci, are now resistant. Nevertheless, sulfonamides can be useful for treatment of urinary tr

26 Sulfisoxazole and sulfamethoxazole are short- to medium-acting agents that are used almost exclusively to treat urinary tract infections. The usual adult dosage is 1 g of sulfisoxazole four times daily or 1 g of sulfamethoxazole two or three times daily. Sulfadiazine achieves therapeutic concentrations in cerebrospinal fluid and in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. Pyrimethamine, an antiprotozoal agent, is a potent inhibitor of dihydrofolate reductase. Sulfadoxine is available only as Fansidar, a combination formulation with pyrimethamine, which is used as a second-line agent in treatment for malaria

27 Sulfasalazine (salicylazosulfapyridine) is widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease Topical Agents Sodium sulfacetamide ophthalmic solution or ointment is effective treatment for bacterial conjunctivitis and as adjunctive therapy for trachoma. Mafenide acetate is used topically to prevent bacterial colonization and infection of burn wounds.

28 Fluoroquinolones The important quinolones are synthetic fluorinated analogs of nalidixic acid. They are active against a variety of gram-positive and gram-negative bacteria. Quinolones block bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. Earlier quinolones (nalidixic acid, oxolinic acid, cinoxacin) did not achieve systemic antibacterial levels. These agents were useful only for treatment of lower urinary tract infections. Fluorinated derivatives (ciprofloxacin, levofloxacin, and others) have greatly improved antibacterial activity compared with nalidixic acid and achieve bactericidal levels in blood and tissues.

29 Ciprofloxacin, enoxacin, lomefloxacin, evofloxacin, ofloxacin, and pefloxacin comprise a second group of similar agents possessing excellent gram-negative activity and moderate to good activity against grampositive bacteria. Gatifloxacin, moxifloxacin, sparfloxacin, and rovafloxacin comprise a third group of fluoroquinolones with improved activity against gram-positive organisms, particularly S pneumoniae and to some extent staphylococci.

30 Antifungal Agents The antifungal drugs presently available fall into several categories: systemic drugs (oral or parenteral) for systemic infections, oral drugs for mucocutaneous infections, and topical drugs for mucocutaneous infections. Clotrimazole Ketoconazole Itraconazole Fluconazole Terbinafine Hydrochloride


Download ppt "DRUG THERAPY OF INFECTIOUS DISEASES. Classification of infectious diseases  According to onset and duration  According to location  According to item."

Similar presentations


Ads by Google