Overview about antibiotic resistance

(Penicillin, carbapenem,
lincosamide, Macrolides,
Aminoglycoside, Tetracycline and
cephalosporins )

Abstract significance, antibiotic resistance

has become a growing concern,
Antibiotics play a vital role in resulting from bacterial
managing bacterial infections mechanisms that neutralize
across various fields, including antibiotic efficacy. This review
human health, agriculture, and addresses the factors contributing
aquaculture. However, the rising to this crisis and explores
challenge of antibiotic resistance innovative solutions to mitigate
diminishes their effectiveness, its impact.
posing a critical threat to public
health. This review explores the Classifications of antibiotics:
mechanisms of antibiotic action,
the emergence and spread of
resistance, and the key factors 1. Penicillin
influencing this phenomenon. It
also highlights promising Mechanism of Action:
alternatives, such as nano • Inhibit bacterial cell wall
antibiotics, bacteriophages, and synthesis by targeting penicillin-
botanicals, to combat this global binding proteins (PBPs), leading to
crisis. bacterial lysis and death.

Keywords Spectrum of Activity:

Antibiotic,resistance,bacteria • Broad, depending on the
subclass:
Introduction • Natural Penicillins: Effective
against Gram-positive bacteria
Antibiotics are chemical (Streptococcus, Enterococcus),
compounds derived from some Gram-negative (e.g.,
microorganisms that inhibit the Neisseria meningitidis).
growth or destroy bacteria. They • Aminopenicillins (e.g.,
are essential in treating bacterial Amoxicillin): Broader spectrum,
infections and are widely used in covering Escherichia coli,
sectors such as human medicine, Haemophilus influenzae.
animal husbandry, and
agriculture. Despite their
 • Penicillinase-resistant (e.g., • Carbapenemase production
Nafcillin): Target Staphylococcus (e.g., KPC, NDM).
aureus. • Efflux pumps and porin
• Extended-spectrum (e.g., mutations in Gram-negative
Piperacillin): Active against bacteria.
Pseudomonas aeruginosa.
Clinical Uses:
Resistance Mechanisms: • Severe infections: sepsis,
• Production of beta-lactamase ventilator-associated pneumonia,
enzymes by bacteria. intra-abdominal infections,
• Alterations in PBPs. meningitis.

Clinical Uses: Side Effects:

• Pneumonia, pharyngitis, • Seizures (especially with
syphilis, meningitis, and Imipenem), nausea, diarrhea, and
endocarditis. hypersensitivity.

Side Effects: Examples: Meropenem,

• Allergic reactions (rash, Imipenem-Cilastatin, Ertapenem.
anaphylaxis), diarrhea, and
potential for C. difficile infection.
3. Lincosamides
Examples: Penicillin G,
Amoxicillin-Clavulanate Mechanism of Action:
(Augmentin), Piperacillin- • Inhibit bacterial protein
Tazobactam (Zosyn). synthesis by binding to the 50S
ribosomal subunit, blocking
2. Carbapenems peptide chain elongation.

Mechanism of Action: Spectrum of Activity:

• Inhibit bacterial cell wall • Effective against:
synthesis by binding to PBPs, • Gram-positive bacteria
similar to penicillins. They are (Staphylococcus aureus, including
resistant to most beta- MRSA).
lactamases. • Anaerobic organisms
(Bacteroides, Clostridium
Spectrum of Activity: perfringens).
• Extremely broad spectrum,
covering: Resistance Mechanisms:
• Gram-positive (Staphylococcus • Ribosomal methylation by erm
aureus, Streptococcus genes.
pneumoniae). • Enzymatic inactivation and
• Gram-negative (Pseudomonas efflux pumps.
aeruginosa, Acinetobacter).
• Anaerobes (Bacteroides Clinical Uses:
fragilis). • Skin and soft tissue infections,
osteomyelitis, dental infections,
Resistance Mechanisms: and aspiration pneumonia.
 • Used as an alternative for
patients allergic to penicillin.
5. Aminoglycosides
Side Effects:
• Diarrhea, nausea, abdominal Mechanism of Action:
pain, and a high risk of C. difficile- • Irreversibly bind to the 30S
associated diarrhea. ribosomal subunit, causing
misreading of mRNA and
Examples: Clindamycin, defective protein synthesis.
Lincomycin.
Spectrum of Activity:
4. Macrolides • Gram-negative bacteria (E. coli,
Pseudomonas aeruginosa).
Mechanism of Action: • Limited Gram-positive activity
• Inhibit bacterial protein when combined with beta-
synthesis by binding to the 50S lactams.
ribosomal subunit, halting
translation. Resistance Mechanisms:
• Aminoglycoside-modifying
Spectrum of Activity: enzymes (AMEs).
• Effective against: • Altered ribosomal binding sites.
• Gram-positive bacteria • Reduced drug uptake.
(Streptococcus pneumoniae, S.
pyogenes). Clinical Uses:
• Atypical bacteria (Mycoplasma • Severe Gram-negative
pneumoniae, Chlamydia infections (e.g., sepsis,
trachomatis). endocarditis).
• Limited Gram-negative activity • Tuberculosis (e.g.,
(Haemophilus influenzae). Streptomycin).

Resistance Mechanisms: Side Effects:

• Methylation of 23S rRNA by • Nephrotoxicity, ototoxicity, and
erm genes. rare neuromuscular blockade.
• Efflux pumps (mef genes).
Examples: Gentamicin,
Clinical Uses: Amikacin, Tobramycin,
• Respiratory infections (e.g., Streptomycin.
pneumonia, sinusitis), STIs (e.g.,
chlamydia), whooping cough, and 6. Tetracyclines
H. pylori eradication.
Mechanism of Action:
Side Effects: • Bind to the 30S ribosomal
• QT interval prolongation, subunit, preventing attachment of
gastrointestinal upset, tRNA to the ribosome.
hepatotoxicity, and drug
interactions via CYP3A4 inhibition. Spectrum of Activity:
• Broad spectrum: Gram-positive,
Examples: Azithromycin, Gram-negative, atypical
Clarithromycin, Erythromycin.
pathogens (Rickettsia, Chlamydia, Clinical Uses:
Mycoplasma). • Surgical prophylaxis (1st gen.),
meningitis (3rd gen.), resistant
Resistance Mechanisms: Gram-negative infections (4th
• Efflux pumps and ribosomal gen.), and MRSA (5th gen.).
protection proteins
Side Effects:
Clinical Uses: • Allergic reactions, diarrhea, and
• Acne, zoonotic diseases (e.g., risk of C. difficile infection.
Lyme disease, Rocky Mountain
spotted fever), chlamydia, and Examples: Cefazolin (1st gen.),
respiratory infections. Ceftriaxone (3rd gen.), Cefepime
(4th gen.), Ceftaroline (5th gen.).
Side Effects:
• Photosensitivity, tooth
discoloration in children, and
The antibiotic classes
gastrointestinal disturbances.
Penicillin,
Examples: Doxycycline, Carbapenems,
Tetracycline, Minocycline. Lincosamides,
Macrolides,
7. Cephalosporins
Aminoglycosides,
Mechanism of Action: Tetracyclines, and
• Inhibit bacterial cell wall Cephalosporins share
synthesis by targeting PBPs. several similarities
Spectrum of Activity: despite their
• Broad spectrum, expanding by differences in spectrum,
generation: mechanism of action,
• 1st Generation: Gram-positive and clinical use. Here’s
cocci (Staphylococcus,
Streptococcus). an analysis of their
• 2nd Generation: Adds some commonalities:
Gram-negative (Haemophilus
influenzae). 1. Antibacterial Mechanism
• 3rd Generation: Expands Gram- • All these antibiotics target
negative coverage essential bacterial functions that
(Enterobacteriaceae). are not present or differ
• 4th Generation: Effective significantly in humans, ensuring
against resistant Gram-negative selective toxicity.
bacteria (Pseudomonas). • Penicillins, Carbapenems,
• 5th Generation: Active against Cephalosporins: Inhibit bacterial
MRSA (Ceftaroline). cell wall synthesis.
• Lincosamides, Macrolides,
Resistance Mechanisms: Aminoglycosides, Tetracyclines:
• Beta-lactamase production, Inhibit bacterial protein synthesis.
efflux pumps, and altered PBPs.
2. Spectrum of Activity
 • All these classes have broad or • Commonly used for respiratory
targeted spectrums of activity, infections (Penicillins,
effective against one or more of Cephalosporins, Macrolides).
the following: • Treat severe, multidrug-
• Gram-positive bacteria resistant infections
(Streptococcus, Staphylococcus). (Carbapenems, Aminoglycosides).
• Gram-negative bacteria • Effective for skin, soft tissue,
(Escherichia coli, Pseudomonas and bone infections
aeruginosa). (Lincosamides, Tetracyclines,
• Atypical pathogens Cephalosporins).
(Mycoplasma pneumoniae,
Chlamydia - Tetracyclines and 6. Side Effects
Macrolides). • All classes share some common
side effects, including:
3. Bacteriostatic vs. • Gastrointestinal issues:
Bactericidal Diarrhea, nausea, and vomiting
• All these classes work by either (common across all classes).
stopping bacterial growth • Allergic reactions: Particularly
(bacteriostatic) or killing bacteria with Penicillins, Cephalosporins,
outright (bactericidal): and Carbapenems.
• Bactericidal: Penicillins, • Superinfections: Risk of
Carbapenems, Cephalosporins, Clostridioides difficile infection
Aminoglycosides. with overuse.
• Bacteriostatic: Lincosamides,
Macrolides, Tetracyclines (may 7. Hospital and Outpatient
become bactericidal in high Relevance
concentrations). • All these classes are
extensively used in both hospital
4. Resistance Mechanisms and outpatient settings:
• All classes face significant • Hospital use: Carbapenems
antibiotic resistance challenges, (severe infections),
including: Cephalosporins (surgical
• Beta-lactamase production: prophylaxis), Aminoglycosides
Affects Penicillins, (sepsis).
Cephalosporins, and • Outpatient use: Penicillins
Carbapenems. (pharyngitis), Macrolides
• Ribosomal mutations or (community-acquired
methylation: Affects Macrolides, pneumonia), Tetracyclines (acne,
Lincosamides, and zoonoses).
Aminoglycosides.
• Efflux pumps: Common 8. Synergistic Use
resistance mechanism across all • Many of these classes are used
classes. in combination therapy for
enhanced efficacy:
5. Clinical Applications • Beta-lactams (Penicillins,
• Each class has both Cephalosporins, Carbapenems) +
overlapping and unique clinical Aminoglycosides: For Gram-
applications: negative infections and
endocarditis.
• Macrolides or Tetracyclines pathogens or polymicrobial
with other agents: For atypical infections.

Here is a table summarizing the key features of the specified

antibiotic classes:

Class Mechanism of Spectrum of Resistance Clinical uses

action activity mechanism
Penicillin Inhibits Effective against Beta-lactamase Respiratory
bacterial cell Gram-positive production; infections,
wall bacteria; some altered PBPs. meningitis,
synthesis by Gram-negative syphilis,
targeting (depending on endocarditis.
PBPs. subtype, e.g.,
aminopenicillins).

Carbapenems Inhibits Broad: Gram- Carbapenemase Severe

bacterial cell positive, Gram- enzymes; efflux multidrug-
wall synthesis negative, and pumps; porin resistant
(broad anaerobes., mutations., infections (e.g.,
spectrum). sepsis, VAP, CRE
infections).

Lincosamides Inhibits Gram-positive Methylation of Skin infections,

bacterial bacteria and 23S rRNA; osteomyelitis,
protein anaerobes (e.g., inducible dental
synthesis by S. aureus, resistance via abscesses,
binding to 50S. Clostridium). erm genes. anaerobic
infections (e.g.,
aspiration
pneumonia).

Macrolides Inhibits Gram-positive Ribosomal Respiratory

bacterial bacteria; some methylation infections (e.g.,
protein Gram-negative (erm genes); CAP), STIs (e.g.,
synthesis by (e.g., efflux pumps chlamydia),
binding to 50S. Haemophilus (mef genes). pertussis, H.
influenzae); pylori infections
atypicals (combination
(Mycoplasma, therapy).
Legionella).

Aminoglycoside Inhibits Gram-negative Aminoglycoside- Severe Gram-

bacterial bacteria (e.g., E. modifying negative
protein coli, enzymes; infections (e.g.,
synthesis (30S); Pseudomonas); altered sepsis,
bactericidal. limited Gram- ribosomal endocarditis),
 positive (in binding sites; tuberculosis
combination with reduced (streptomycin).
beta-lactams). permeability.

Tetracycline Inhibits Broad: Gram- Efflux pumps; Acne, zoonotic

bacterial positive, Gram- ribosomal diseases (e.g.,
protein negative, and protection Lyme disease,
synthesis by atypicals proteins. brucellosis),
binding to 30S. (Chlamydia, respiratory
Rickettsia). infections, STIs
(e.g.,
chlamydia).

Cephalosporins Inhibits Broadening Beta-lactamase Seurgical

bacterial cell spectrum by production; prophylaxis (1st
wall synthesis generation: 1st altered PBPs. gen.),
by targeting (Gram-positive) meningitis,
PBPs. → 4th (Gram- sepsis,
negative and pneumonia,
resistant resistant Gram-
bacteria). negative
infections (3rd-
4th gen.).

This table highlights the mechanism of action, spectrum,

resistance mechanisms, and clinical applications for each
antibiotic class.

Causes of Antibiotic Resistance 1. Increased morbidity and

1. Overprescription and misuse: mortality: Resistant infections claim
Unnecessary and incorrect thousands of lives annually.
antibiotic prescriptions. 2. Economic burden: Estimated
2. Agricultural overuse: Antibiotics global costs: $20 trillion by 2050.
as growth promoters in livestock. 3. Threatened medical
3. Lack of new antibiotics: advancements: Organ transplants,
Insufficient investment in research cancer chemotherapy and surgery
and development. rely on effective antibiotics.
4. Poor infection control: 4. Food security risks: Resistant
Inadequate hospital hygiene and bacteria in agriculture compromise
sterilization. food safety.

Consequences Combating Antibiotic Resistance

1. Improved prescribing practices: 1. Personalized medicine: Targeted
Enhanced stewardship programs. antibiotic therapy.
2. New antibiotic development: 2. Antibiotic stewardship programs:
Incentivizing research and Real-time monitoring and feedback.
development. 3. International cooperation: Global
3. Public awareness campaigns: surveillance and sharing best
Educating patients and healthcare practices.
professionals.
4. Infection control measures: Conclusion
Enhanced hospital hygiene and Antibiotic resistance demands
sterilization. immediate attention. Collective
5. Alternative therapies: Exploring efforts from healthcare
non-antibiotic treatments. professionals, policymakers,
industry leaders and the public are
Future Directions necessary to mitigate this growing
threat.

References
1. World Health Organization. (2022). Antibiotic resistance.
https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance
2. Centers for Disease Control and Prevention. (2022). Antibiotic resistance
threats. https://www.cdc.gov/drugresistance/biggest-threats.html
3. The Lancet. (2022). Global burden of antibiotic-resistant infections,
399(10325), 629-655.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00476-9