Ensuring that the choice of antimicrobial is appropriate, for the right indication and given at the right dose and for the right duration. The appropriate choice of antimicrobial agent depends on the nature of the infection and the sensitivity pattern in the local regional hospital. In the presence of pus or necrotic tissue, AMA should only be used after surgical intervention. e) AMA should not be prescribed empirically.
In the 1980s, the fluorinated derivatives of 4-quinolones such as ciprofloxacin and its analogues were introduced. Increase in the blood concentration of theophylline is seen in the presence of some of the quinolones (except Ofloxacin, Levofloxacin, Sparfloxacin and Lemofloxacin). These proteins are transpeptidases and carboxypeptidases that catalyze the terminal reaction in bacterial cell wall synthesis.
Structural differences in the bacterial cell wall of Gram+ve and Gram-ve bacteria affect the organism's sensitivity to these agents by influencing AMA binding and penetration. AMAs are lethal during the bacterial reproduction phase, as cell wall synthesis takes place during this phase. Hypersensitivity to penicillins is directly proportional to the duration and total dose of penicillin received in the past.
In some cases, the administration of these broad-spectrum AMAs can lead to changes in the intestinal bacterial flora, which can lead to super-infection with microorganisms not sensitive to penicillin.
Cephalosporins
The aminoglycosides are highly polar agents, they are active in alkaline pH and are therefore not absorbed from the digestive tract. These AMAs penetrate the bacterial cell wall through pores present on the bacterial cell wall, through a process of passive diffusion. It is observed that the bacterial cell wall weakened by the action of penicillin facilitates the diffusion of aminoglycosides.
Aminoglycosides bind to the 30 S subunit of the bacterial ribosome and inhibit protein synthesis. Aminoglycosides inhibit protein synthesis by interfering with the formation of an initiation complex leading to the accumulation of this abnormal initiation complex. Thus, a prolonged bactericidal effect is seen even after the concentration of aminoglycosides falls below the Minimum.
Inactivation of the aminoglycosides by enzymes such as acetyltransferase, phosphotransferase and adenyltransferases present in the bacterial cells. The microorganisms modify their bacterial cell surface such that there is a failure of the AMAs to diffuse across the bacterial cell wall. One of the ways to overcome this kind of resistance is to combine β-lactam AMA with the aminoglycosides.
The former will weaken the bacterial cell wall enabling the aminoglycosides AMA to penetrate the microorganism and inhibit their protein synthesis. Mutation and subsequent alteration of the 30 S ribosomal subunit there by preventing the attachment of AMA to the ribosome. Commonly used aminoglycosides are streptomycin, gentamicin, cisomycin, netilmicin, kanamycin, amikacin, neomycin, tobramycin, soframycin, spectinolysin, paromonusin.
The dose in such patients should be adjusted according to the serum creatinine level. Vestibular and cochlear sensory cells are sensitive to the effect of aminoglycosides, which causes their destruction. It is important to remember that penicillins, cephalosporins, amphotericin B and heparin should not be mixed in the same vial, as this causes in vitro interaction and inactivation of aminoglycosides.
Macrolide Antimicrobial Agents
These effects are seen more frequently in patients suffering from myasthenia gravis or in the presence of other concomitantly administered skeletal muscle relaxants. Urinary tract infections: Gentamicin alone or in combination with penicillin or cephalosporin is the treatment of choice. For sepsis: Fever and septicemia in patients with a weakened immune system, gentamicin is used in combination with penicillin.
Meningitis due to β-lactam-resistant organisms: Gentamicin can be given both systemically and intrathecally; the drug can be administered simultaneously by these two routes. Miscellaneous - In patients undergoing peritoneal dialysis, an aminoglycoside is used topically along with the dialysis fluid in sepsis due to Pseudomonas infection. Mechanism of action: Macrolides inhibit protein synthesis in bacteria by reversibly binding to the 50 S ribosomal subunits, preventing translocation of tRNA by bacteria.
In patients with streptococcal or pneumococcal infections known to cause pharyngitis, sinusitis, otitis media, pneumonia and respiratory infections, sinusitis macrolides are used as substitutes for penicillin, especially if the patients cannot tolerate penicillins. 2. Prophylactic uses of erythromycin fever include prevention of bacterial endocarditis after dental or respiratory tract surgery. They work by reducing the release of pro-inflammatory cytokines from the phagocytes and are therefore useful in the management of rheumatoid arthritis, cystic fibrosis, asthma, chronic sinusitis, etc.
Erythromycin is used in diabetic gastroparesis because AMA acts as a motilin receptor agonist. Cholestatic hepatitis has been reported with erythromycin estheolate and rarely with ethyl succinate or stearate. High doses of erythromycin may cause transient reversible hearing impairment (hearing loss). Azithromycin in therapeutic doses can cause the development of tinnitus.
Administration of erythromycin steolate to infants may lead to the development of hypertrophic pyloric stenosis. Drug Interactions: Erythromycin and Clarithromycin are both inhibitors of the cytochrome P450 enzyme system, which may increase blood concentrations of carbamazepine, theophylline, warfarin, cycloserine, and pimozide. This drug interaction is not observed with azithromycin as it does not affect the p450 enzyme in the liver.
Miscellaneous Antimicrobials
It is administered orally as an alternative to vancomycin for the treatment of iatrogenic pseudomembranous colitis. Mechanism of action: It is bacteriostatic to 'resting bacilli' and bactericidal to rapidly dividing intracellular organisms present in macrophages as well as organisms in the extracellular region. For the treatment of pulmonary and extrapulmonary tuberculosis, it is administered in combination with other first-line antitubercular drugs.
Resistance: Resistance to ethambutol rarely occurs, especially when given in combination with other antituberculosis drugs. It is not effective against any other organisms, as they have an efficient pyrazinoic acid efflux mechanism and thus do not allow the drug to accumulate in the mycobacterial cell. Pharmacokinetics: It is well absorbed from the GIT and is widely distributed in most body tissues.
It also finds benefit in patients with drug-induced hepatotoxicity when co-administered with ethambutol. Pharmacokinetics: Effectively absorbed after oral administration and widely distributed in body fluids including CSF. Use: It is useful in the treatment of TB meningitis, renal tuberculosis and for the treatment of multi-drug resistant (MDR) tuberculosis.
Because of its low cost, it is used in combination with INH in many developing countries. It is active against both intracellular and extracellular M .tuberculosis including the atypical organism. It is well absorbed orally and given at a maximum dose of 1 g/day which may cause severe GI side effects.
With the emergence of multidrug-resistant (MDR) tuberculosis and the association of complex infections with AIDS, it is imperative that new drugs and strategies be developed to treat TB in these situations. It is most widely used in the treatment of leprosy and remains the drug of choice despite the development of a large number of other sulfones. Mechanism of action: It is a week bactericidal against M.Leprae and preferentially binds to the mycobacterial DNA, thereby inhibiting the template function of DNA.
It is widely distributed, including the phagocytes, and is stored in the reticulo-endothelial cells, from which it is slowly released. There is a biological delay of 6-7 weeks before the drug's effect is manifested, and it is therefore important to administer clofazamine as part of multidrug therapy.
