CEPHALOSPORIN - antibiotics, full details

Cephalosporins are β-lactam antimicrobials used to manage various infections caused by both gram-positive and gram-negative bacteria. Cephalosporins are categorized into 5 generations based on their spectrum of coverage against gram-positive and gram-negative bacteria and their temporal discovery.

1. CEPHALOSPORIN
SOUSAN
A274153121006
HG&MM

2. INTRODUCTION
➢Antibiotics are compounds that target bacteria and, thus, are intended to treat
and prevent bacterial infections.
➢The term "antibiotics" literally means "against life," in this case, against
microbes.
➢This activity will examine the various classes of antibiotics, their mechanisms of
action, bacterial susceptibilities, and potential adverse events.

3. CLASSIFICATION OF ANTIBIOTICS
Based on the mechanism of action
Based on the spectrum of activity
Based on the mode of action

5. BETA -LACTAMS ANTIBIOTICS
➢Agroup of drugs that contain a beta-lactam ring in their chemical structure.
➢They are bactericidal agents that work by interfering with the structural
crosslinking of peptidoglycans in bacterial cell walls.
➢Active against many gram-positive, gram-negative, and anaerobic organisms.
➢Penicillins, Cephalosporins, Cephamycins, Monobactams, Carbapenems,
Carbacephems, and Beta-lactamase inhibitors.

6. CEPHALOSPORINS
➢Any of a group of widely used broad-spectrum antibiotics, isolated initially as a
product of fermentation from the fungus Cephalosporriumacremonium,are
called Cephalosporins.

7. HISTORY
➢The Cephalosporines are isolated from:
>Cephalosporiumspecies
>Prepared semisyntheticallyfrom Acremonium
chrysogenum(Cephalosporin C (CPC))
➢The first chemical compounds of the cephalosporin
group were isolated from Cephalosporiumacremonium,
a cephalosporin-producing fungus, first discovered by
Giuseppe Brotzuin 1948.

8. CHEMISTRY OF CEPHALOSPORIN
➢It has a bicyclic system containing a four-membered
beta-lactam ring fused to a six-membereddihydro
thiazidering system
➢Nucleus of the most cephalosporin is sevenamino-
cephalosporanicacid (7-ACA)
➢Possible modifications:
> 7-Acylamino side chain
> 3-Acetoxymethyl side chain
>Substitution at C-7

9. PROPERTIES OF CEPHALOSPORIN
Broad
spectrum
activity
They are
water
soluble
Relatively
stable to
pH and
temperatu
re changes
Their
activity is
not
reduced by
serum

10. CLASSIFICATION
➢Cephalosporins are antimicrobials grouped into five generations based on their
temporal discovery and spectrum of coverage against gram-positive and gram-
negative bacteria.
➢The generations differ mainly in the antibacterial spectrum, with differences
within a generation being mostly pharmacokinetic.

12. FIRST GENERATION
➢Include cefazolin, cephalothin, cephapirin, cephradine, cefadroxil, and cephalexin.
➢They primarily target gram-positive cocci like Staphylococci spp. and Streptococci spp.
➢Limited coverage against gram-negative bacteria, with some susceptibility seen in Proteus
mirabilis, E. coli, and Klebsiella pneumoniae.
➢Oral first-generation cephalosporins commonly used for uncomplicated skin and soft tissue
infections, bone infections, respiratory tract infections, genitourinary tract infections, biliary
tract infections, bloodstream infections, otitis media, and surgical prophylaxis.
➢Cefazolin is preferred for surgical prophylaxis.
➢Non-FDA-approved indication includes endocarditis prophylaxis for susceptible individuals
undergoing dental or respiratory procedures.

13. SECOND GENERATION
➢Examples include cefuroxime, cefprozil(second-generation subgroup), cefmetazole, cefotetan, and cefoxitin
(cephamycin subgroup).
➢Cefuroxime has increased coverage against H. influenzae and is indicated for Lyme disease in pregnant women
and children.
➢Cephamycin subgroup has increased coverage against Bacteroides species.
➢Second-generation cephalosporins have decreased activity against gram-positive cocci compared to first-
generation but increased activity against gram-negative bacilli.
➢Prescribed for respiratory infections like bronchiolitis or pneumonia.
➢Indications similar to first-generation cephalosporins, including bone, respiratory tract, genitourinary tract, biliary
tract, bloodstream infections, otitis media, and surgical prophylaxis.
➢Coverage includes H. influenzae, Enterobacter aerogenes, Neisseria species, Serratia marcescens, and gram-
negative bacteria covered by first-generation cephalosporins.

14. THIRD GENERATION
➢Third-generation cephalosporins: cefotaxime, ceftazidime, cefdinir, ceftriaxone, cefpodoxime,
cefoperazone, cefixime.
➢Extended gram-negative bacteria coverage.
➢Used for gram-negative infections resistant to first and second-generation cephalosporins or
other beta-lactam antimicrobials.
➢IV administration allows penetration of the blood-brain barrier, effective against bacteria in
cerebrospinal fluid, notably ceftriaxone and cefotaxime.
➢Ceftriaxone treats meningitis caused by H. influenzae, Neisseria meningitidis, or Streptococcus
pneumoniae, also used for gonorrheaand disseminated Lyme disease.
➢Ceftazidime crucially covers Pseudomonas aeruginosa.

15. FOURTH GENERATION
➢Fourth-generation cephalosporin: cefepime.
➢Broad-spectrum antimicrobial penetrates cerebral spinal fluid.
➢Additional quaternary ammonium group enhances penetration of outer membrane of
gram-negative bacteria.
➢Covers Streptococcus pneumoniae and methicillin-sensitive Staphylococcus aureus (MSSA)
like cefotaxime and ceftriaxone.
➢Crucially covers Pseudomonas aeruginosa like ceftazidime.
➢Provides coverage against beta-lactamase-producing gram-negative bacilli.
➢Reserved for serious systemic infections with multi-resistant organisms due to its broad
spectrum.

16. FIFTH GENERATION
➢Fifth-generation cephalosporin: ceftaroline.
➢Broad-spectrum antimicrobial covering susceptible gram-positive and gram-
negative organisms.
➢Unique for its coverage against methicillin-resistant Staphylococcus aureus
(MRSA).
➢Covers Listeria monocytogenes and Enterococcus faecalis.
➢Does not cover Pseudomonas aeruginosa.

17. MECHANISM OF ACTION
➢Cephalosporins inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins
(PBPs) via their beta-lactam rings.
➢This prevents cross-linking of peptidoglycan units, leading to bacterial cell death.
➢Staphylococcus aureus can develop resistance to cephalosporins by modifying penicillin-
binding proteins, leading to methicillin-resistant Staphylococcus aureus (MRSA).
➢Only fifth-generation cephalosporin, ceftaroline, has coverage against MRSA.
➢Another resistance mechanism is the production of beta-lactamase enzymes, which cleave
beta-lactam rings and inactivate cephalosporins.
➢Beta-lactamase inhibitors can be combined with cephalosporins to enhance their activity,
e.g., ceftazidime/avibactam and ceftolozane/tazobactam.

20. Cephalosporin
Act as transpeptidase enzyme
Inhibit peptidoglycan synthesis
Activation of autolytic enzyme
Increase the permeability of the cell membrane
Cell explodes and lysed
Death of microorganism

21. CEPHALOSPORIN C
➢The conversion of cephalosporin C to 7-ACA.
➢Achieving one-step bioconversion using cephalosporin C acylase (CCA).
➢C-3 and C-7 are indicated in 7-ACA, the two carbon sites subjected to different
side chain modifications to synthesize various cephalosporin antibiotics.
➢The acyclic amide bond and the amide bond in the beta-lactam ring.

23. ADMINISTRATION

24. ADVERSE EFFECTS
➢Common: Nausea, vomiting, lack of appetite, abdominal pain
➢Hypersensitivity reaction
➢Drug-Induced Immune Hemolytic Anemia (DIIHA)
➢Disulfiram-like reaction
➢Vitamin K deficiency
➢ Increased nephrotoxicity of aminoglycosides
➢Pseudomembranous colitis

25. TOXICITY
➢High dosage cephalosporins may cause nephrotoxicity by affecting the
mitochondria system of the kidney.
➢Cefepime overdose can lead to seizures and encephalopathy, possibly due to its
concentration-dependent ϒ-aminobutyric acid (GABA) antagonism.
➢Altered mental status and triphasic wave discharge on EEG observed with
cefepime overdose; discontinuation results in normalization of mental status.
➢Caution is advised when using cephalosporins in patients with a history of
seizures, particularly in those with poor renal function.

26. DIFFERENCES BETWEEN PENICILLIN AND CEPHALASPORIN
PENICILLIN
➢Penicillin is an antibiotic drug we use
against many bacterial infections
➢Low cure rate
➢More susceptible to beta-lactamases
CEPHALOSPORIN
➢Cephalosporin is a group of beta-lactam
antibiotics derived from the fungus
Acremonium
➢High cure rate
➢Less susceptible to beta-lactamases

27. RESISTANCE MECHANISMS AGAINSTCEPHALOSPORINS
➢ Antibiotic resistance against cephalosporins primarily occurs through three mechanisms:
(i) Beta-lactamases are produced by bacteria, which hydrolyze the beta-lactam ring of
cephalosporins.
(ii) Alterations in penicillin-binding proteins (PBPs), the target proteins of cephalosporins,
resulting in reduced affinity or development of novel PBPs.
(iii) Reduced antibiotic penetration due to low membrane permeability, often caused by
structural or quantitative changes in porin, an outer membrane protein.
➢ Resistance can be intrinsic or acquired through mobile genetic elements like chromosomes,
plasmids, transposons, or integrons, enabling horizontal transfer between bacteria.
➢ Combining cephalosporins with beta-lactamase inhibitors (e.g., ceftazidime-avibactam or
ceftolozane-tazobactam) can enhance bactericidal action, even against resistant strains.

28. CONCLUSION
➢Effective interprofessional teamwork is crucial for providing optimal patient care.
➢ Clear roles and trust between team members increase efficiency.
➢ Effective communication skills essential for accurate diagnosis, prescription, and monitoring
of adverse effects.
➢ Pharmacists educate patients on medication administration and potential adverse effects
and verify agent selection and interactions.
➢ Patients play a crucial role by informing the healthcare team about their experiences and any
unusual symptoms.
➢ Through effective teamwork, appropriate management of cephalosporin adverse drug
reactions leads to better patient outcomes.

29. THANK YOU
REFERENCES:
https://www.ncbi.nlm.nih.gov/books/NBK551517/
https://www.ncbi.nlm.nih.gov/books/NBK535443/#:~:text=Antibiotics%20are%20compounds%2
0that%20target,susceptibilities%2C%20and%20potential%20adverse%20events.
https://www.sciencedirect.com/science/article/abs/pii/B9780444635037000024