Pathology 21

• Alexander Fleming, discoverer of penicillin, stated that he didn't plan to revolutionise all medicine by discovering the world's first antibiotic, but he did.
• Crude mortality rates for all causes, non infectious causes and infectious diseases over the period 1900 - 1996.
• Resistance to penicillin was foreseen early, with the concern that ignorant individuals may easily under dose themselves and make their microbes resistant.
• Antibiotic target site is a crucial aspect of antimicrobial therapy.
• Discovery of penicillin revolutionised treatment of infectious disease, increased life expectancy due to ability to prevent and treat infection.
• Combination therapy is used for synergistic effects between two drugs, polymicrobial infections, and to avoid antagonistic effects.
• Bacteriocidal antibiotics are able to kill or lyse bacterial cell, while bacterial multiplication does not resume even when the antibiotic is removed.
• There are four main mechanisms of action: inhibition of cell wall synthesis, inhibition of protein synthesis, inhibition of DNA replication/synthesis, and inhibition of folate synthesis.
• Antibiotics are substances produced by organisms that have inhibitory effects on other organisms, while synthetic drugs are produced in a lab.
• Broad Spectrum Antibiotics include agents which are active against many Gram-positive and Gram-negative bacteria, while Narrow Spectrum Antibiotics act on certain types of bacteria only.
• Narrow spectrum antibiotics act on certain types of bacteria only, with some exceptions.
• Bacteriostatic antibacterials inhibit the growth of bacteria, while bactericidal antibacterials kill bacteria.
• Concentration-dependent antibiotics, such as aminoglycosides and fluoroquinolones, have a peak concentration/minimum inhibitory concentration (C max /MIC) ratio and/or the area under the concentration-time curve at 24 h/MIC (AUC 0 - 24 /MIC) ratio that correlates with efficacy.
• Peaks & Troughs refer to the serum antibacterial levels for drugs with a narrow therapeutic index, too high a level can lead to drug toxicity, while too low a level can lead to therapeutic range.
• Antimicrobial susceptibility testing uses standardized criteria, such as CLSI and EUCAST, for MIC determination.
• Researchers have had to implement continuous surveillance activities for resistance patterns due to the mutations in bacterial DNA.
• On a larger scale, AST aids in the evaluation of treatment services provided by hospitals, clinics, and national programs for the control and prevention of infectious diseases.
• Antimicbial stewardship evaluate the clinical response to treatment.
• Inappropriate and/or delayed appropriate antibiotic use in the ICU has been shown to have an impact on morbidity and mortality.
• Antibacterials are substances that inhibit the growth of or kill bacteria or other microorganisms, including bacteria, viruses, fungi, and protozoa.
• Antimicrobial susceptibility testing (AST) is a laboratory procedure performed by medical technologists (clinical laboratory scientists) to identify which antimicrobial regimen is specifically effective for individual patients.
• Use a narrow-spectrum antibiotic whenever possible, appropriate empirical choice for nosocomial sepsis, requires initial broad-spectrum antibiotics, even a combination, until culture and AST results are back and de-escalation should be implemented.
• Pharmacodynamics is the study of the interaction between a drug and the body, including the effects of concentration at the site or exposure time for the drug, duration of use, and the effects of concentrated dosing.
• Time-dependent antibiotics, such as beta-lactams, including penicillins and penems, glycopeptides, linezolid, macrolides, etc., have a peak concentration/minimum inhibitory concentration (C max /MIC) ratio that correlates with efficacy.
• Penicillin hypersensitivity occurs in 0.4 - 10% of patients and can lead to mild rash or severe anaphylaxis and death.
• Rare adverse effects of penicillins include haemolysis and nephritis.
• Cephalosporins are good alternatives to penicillins when a broad-spectrum drug is required and should not be used as first choice unless the organism is known to be sensitive.
• Second generation cephalosporins include cefaclor and cefuroxime and are active against enterobacteriaceae such as E. coli, Klebsiella spp, Proteus spp.
• Ampicillin is less active than benzylpenicillin against Gram-positive bacteria but has a wider spectrum including Enterococcus faecalis, Haemophilus influenzae and some Escherichia coli, Klebsiella and Proteus strains.
• Phenoxymethylpenicillin (Penicillin V) is acid stable and is given orally for minor infections.
• Amoxycillin is similar but better absorbed orally and is sometimes combined with clavulanic acid, which binds strongly to β-lactamase and blocks the action of β-lactamase in this way.
• Cephalosporins are produced from a fungus Cephalosporium acremonium.
• Cephalosporins are bactericidal and modify cell wall synthesis, interfering at the final step of peptidoglycan synthesis (Transpeptidation).
• First generation cephalosporins include cefadroxil, cefalexin, cefadrine and are most active against Gram-positive cocci.
• Fourth generation cephalosporins include cefpirome and are better against Gram-positive than third generation.
• Cephalosporins are classified into first, second, third, and fourth generations.
• Third generation cephalosporins include cefixime and other IV cefotaxime, ceftriaxone, ceftazidime.
• Diarrhoea is common with ampicillin, less common with amoxycillin.
• Ampicillin is acid stable, is given orally or parenterally, but is β-lactamase sensitive.
• Cephalosporins owe their activity to a β-lactam ring and are bactericidal.