Antibiotics

Disclaimer

• Allopathy medicine awareness article for doctors & hospitals.

• Can't cover everything in this small article

• Won't cover antivirals, Antifungals, Anthelminthic drugs here

• Lots will remain unanswered

• Not everyone will be happy

• But everyone will take something home

• All we can do is initiate a curiosity of research and understand what is wrong/right

Wordplay

• Antibiotics

  • Antibacterial

• Antimicrobial

  • Antiviral

  • Anthelminthic

  • Antifungal

  • Antibacterial

Case Discussion 1 -

A 55 year lady, was operated for hysterectomy 5 days back. She went home, started having fever 2 days back and now brought with altered sensorium, Low urine Output. On Examination, HR=130, Pulse Feeble BP=80/50 RR=38 SPO2 - 92% on air CVS - cold extremities CNS - Confused, drowsy

What do you think could have happened?

• What is septicemia / Bacteremia?

• What is sepsis?

What will you do?

• Give Antibiotics?

• Which one??

Likely Pathogens - Seek information from local Pathologist/Microbiologist Life is a constant fight against infection

• Bacteria are all around us

• Skin, Gut, Air, Soil, ….

But Bacteria is not always Bad

• Gut bacteria

• Problems with antibiotics

  • Harmful bacteria grow

• Probiotics

  • Daralac, Sporolac, Curd, Vitamin B, etc.,

• Normal vs C-Section babies exposure to mother's bacteria is different.

Why does infection occur?

• Weakened defenses or hygiene problem

• Pathogenic bacteria enter from other locations

• Salmonella

Back to case discussion on Septicemic Shock

How Bacteria enters the body? - Portal of Entry

• Skin

• Upper Respiratory Tract

• GI Tract

• Urogenital Tract

• Tubes and Punctures - including bites

Skin and Soft Tissue Infection SSTI

Skin, subcutaneous tissue, fascia, and muscle

• Impetigo

• Folliculitis

• Furuncle

• Carbuncle

• Erysipelas

• Cellulitis

• Necrotizing Fascitis

Organisms causing skin and soft tissue infection

• Gram Positive Cocci - Staphylococcus aureus

• Streptococcus pyogens

• Site specific - gram negative bacilli in Perianal abscess

• Immunocompromised - pseudomonas, enterococcus

Classification of Bacteria

• Cocci (ball) & Bacilli (rod)

• Gram Positive (Changes to Purple) & Negative (Pink)

• Aerobic (w/ O2) & Anaerobic (w/o O2)

• Skin infections are usually Gram Positive Cocci

Empiric Therapy

There are hundreds of antibiotics

• Why so many antibiotics needed?

  • Resistance, side effects, many new bacteria growth

• How antibiotics work?

  • Most drugs act on patient, his organs, receptors

  • Antibiotic should be toxic to the bacteria but not to humans

Cell wall and Ribosome 70S are two things that differentiate bacteria from us.

Antibiotics that inhibit Cell Wall Synthesis

• More than 60% antibiotics act by inhibiting cell wall synthesis

• Beta Lactam Antibiotics

• Glycopeptides

• Penicillin

General structure of Penicillins

• Beta-Lactam Ring -> Beta Lactamase -> enzymes -> Bacterias shared those enzymes

• Doctors started Beta Lactamase Inhibitors

  • Amoxicillin + Clavulanic acid is used to treat certain infections caused by bacteria, including infections of the ears, lungs, sinus, skin, and urinary tract. Amoxicillin is in a class of medications called penicillin-like antibiotics. It works by stopping the growth of bacteria.

  • Piperacillin + tazobactam, sold under the brand name Zosyn among others, is a combination medication containing the antibiotic piperacillin and the β-lactamase inhibitor tazobactam. The combination has activity against many Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa

  • Unasyn (Ampicillin + Sulbactam) is a combination antibiotic medication containing ampicillin and sulbactam. It is used to treat a wide variety of bacterial infections -

    • meningococcal meningitis.

    • bacterial meningitis caused by Streptococcus.

    • infection of the biliary tract.

    • pneumonia caused by bacteria.

    • diverticulitis.

    • E. coli bacteria infection of abdominal cavity lining.

    • Klebsiella pneumoniae infection of abdominal cavity lining.

Cephalosporin

• Skin infections - Gram +ve - Amoxicillin + Clavulanic acid (Gen 1, 2)

• Intra abdominal / cepsis - Gram -ve - Piperacillin + tazobactam (Gen 3,4)

Upper Respiratory Tract

• Nasopharyngeal infection

• Sinusitis

• Otitis media

• Epiglottitis

• Laryngitis

• Tracheobronchitis

• Pneumonia

Organisms causing URTI

• Rhinoviruses

• Coronaviruses

• Adenoviruses

• Coxsackieviruses

• In general adult URTI is by these viruses, So don't give antibiotics. Administer steam, decongestant, anti-inflammatory, etc.,

• 8-10-12 age kids can get Gram Positive Cocci bacteria - Streptococcus. If not treated well it can turn into Rheumatic fever & Rheumatic heart disease. Amoxicillin / Co-amoxiclav / Ampicillin can be administered.

• Non typeable H influenzae, and Moraxella catarrhalis

Lower Respiratory Tract

• Pneumonia

  • Community acquired

    • Pneumonaiae, H.influenzae, Legionnella, E.coli, Klebsiella sp., S.aureus

    • Levofloxacin 500 OD (7 days)

    • Amoxycillin 500 - 1gm TDS

    • IV Mox-clav 1.2 gm TDS or Ceftriaxone 2 gm OD

    • Upgrade - (Escalate quickly, deescalate slowly)

      • Piperacillin Tazobactam

      • Meropenem

      • Cefoperazone sulbactam

      • MRSA is a doubt

        • Linezolid 600 IV / Oral BD

      • Atypical - Doxycline 100 BD or Azithromycin 500 OD
        

• Hospital acquired

  • Entero-bacteriaceae, Pseudomonas spp., Acinetobacter spp. (Gram -ve)

  • Treatment

    • Piperacillin-tazobactam 4.5g IV q6h or Cefoperazone-sulbactam 3g IV q8h

    • Upgrade -

      • Imipenem 1g IV q8h or meropenem

  • Modify based on culture of lower respiratory secretions.
    

Antibiotics that inhibit Ribosome 50s Macrolides

• More effective in Lung infections because they concentrate in Lung macrophages

• Thromycin

• Erythromycin

• Azithromycin

• Roxithromycin

Cidal and Static

• Those antibiotics which kill the bacteria are bactericidal. E.g., Beta lactams, Floxacin

• Those which inhibit the growth of bacteria without killing it are termed bacteriostatic

  • E.g., Doxycline, Macrolides

• If patient has taken antibiotics in past 90 days, then we don't give static antibiotics.

GI Tract

• Diarrhea

• Intraabdominal infection

• Parasitic infection

• Salmonella

Acute Gastroenteritis

• Viral

• Enterotoxigenic E Coli

• Treatment

  • Rehydration

  • No Antibiotics (unless Dysentery)

  • If Dysentery - Metronidazole, Nitazoxamide, Diloxanide Furate (for amoebic)

  • Ciprofloxacin 500 BD for bacillary dysentery

Enteric Fever / Typhoid

• Cephalosporin

• Oral - Cefixime 200 BD 14 days / Azithromycin 500 BC x 7 days

• IV - Ceftriaxone 2 gm IV BD

Intra abdominal infections

• Biliary tract infections (cholangitis, cholecystitis)

• Spontaneous bacterial Peritonitis

• Secondary peritonitis, Intra-abdominal abscess / GI perforation

• Post necrotizing pancreatitis: infected pseudocyst; pancreatic abscess

• Sick Patient, upgrade to -

  • Piperacillin/tazobactam 4.5 gm IV 8 Hrly

  • Addition of cover for yeast (fluconazole IV 800 mg loading dose day 1, followed by 400 mg 2nd day onwards)

  • Enterococcus (vancomycin / teicoplanin) may be contemplated

Gram Negative Bacteria (Bacilli - rods)

• Enterobacteriaceae

  • E Coli

  • Klebsiella

  • Proteus

• Shigella / Salmonella

• Pseudomonas (It’s a monster. Administer: Piperacillin Tazobactam)

• Severe

  • Meropenem 1 gm IV 8 hrly

  • Or

  • Imlpenem Cilastatin 500 mg IV 6 hourly

  • To cover Anaerobic - Metronidazole 400 8hrly IV

Antibiotics for Enterobacteriaceae

• Third Generation Cephalosporins

  • Ceftriaxone 2gm IV OD

  • Cefoperazone Sulbactam

• Fluoroquinolones

• Floxacins

Anaerobic Bacteria

• Clostridium

• Peptostreptococcus

• Bacteroids

Anaerobic Bacteria - Classification

1. Gram-negative bacilli (curved, spirals & spirochete forms) - Bacteroids, Borrelia, Butyrivibrio, Capnocytophaga, Campylobacter, Fusobacterium, Leptotrichia, Porphyromonas, Prevotella, Treponema, etc.,

2. Gram-positive cocci - Anaerococcus, Coprococcus, Micromonas, Peptococcus, Peptostreptococcus, Streptococcus, Gemella, etc.,

3. Nonsporing Gram-positive bacilli - Actinomyces, Arcanobacterium, Bifidobacterium, Eubacterium, Lactobacillus, Methanobacterium, Mobiluncus, Propionibacterium, etc.,

4. Gram-negative cocci - Acidaminococcus, Anaeroglobus, Veillonella

Anaerobic Bacteria coverage

• Metronidazole / Tinidazole tab 400 mg / IV

  • For groin, vagina, belly region (abdomen and Genito-urinary tract) coverage

• Clindamycin - C 150 mg

  • Any other region coverage than groin, belly region said for Metronidazole.

  • Suppresses protein synthesis by binding to 50S ribosomal subunits

  • Anaerobic Bacteria

  • Bite wounds

  • PID

Genitourinary Tract

• Acute uncomplicated Cystitis

• Acute uncomplicated Pyelonephritis

  • Enterobacteriaceae

  • Streptococcus saprophyticus

Choice of Antibiotics in Acute uncomplicated UTI

• Levofloxacin 500 OD (not effective nowadays)

• Nitrofurantoin 100 mg BD x 5 Days (old drug, sulpho based, first choice in US)

• Bactrim DS (Cotrimoxazole)

• Fosfomycin

  • Fosfomycin is a bactericidal, activity against several bacteria including multidrug resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis.

  • Acute Cystitis

  • Multi-drug resistant UTI: 2-3 g PO every 2-3 days for 3 doses

Aminoglycosides - For Hospitalized UTI

• Gentamycin

• Amikacin

• Piperacillin/tazobactam

• Monitor renal function closely and rationalize according to culture report

• Complete total duration of 14 days

Tubes and Punctures

• Endocarditis

• Vehicle borne diseases

If it is Tubes & Punctures, its Hospital related

• Causative Organism - Pseudomonas (Gram-ve in immunocompromised patients, blue-green), Klebsiella, Enterococcus, MRSA

• Piperacillin/tazobactam

• Meropenem

• Clindamycin

• Vancomycin

Anti Pseudomonas

• Antipseudomonal beta lactam

  • Piperacillin

  • Ceftazidime

  • Cefepime

  • Imipenem

  • Aztreonam

• +

• Aminoglycoside

  • Tobramycin

  • Gentamycin

  • Amikacin

  • or

  • Fluoroquinolones

    • Ciprofloxacin

    • Levofloxacin

MRSA (Gram +ve)

• Antibiotics

  • Glycopeptides (Safegaurd these, as the bacteria can become sensitive to these kind)

    • Vancomycin

      • Gram +ve Cocci Staphylococcus, MRSA

    • Teicoplanin

      • Gram +ve Bacteria including Enterococcus, MRSA

Factors in choice of Antibiotics

• Supposed causative organism

• Spectrum of activity

• Penetration in target tissues

• Metabolism of antibiotic and interaction

• Patient's overall condition

• Route of administration

• Timing of dosage - with food

• Cidal or static

• Bioavailability

Three types of antibiotic treatment

• Prophylactic

  • The person is not infected yet but has high chances

  • HCQS

  • Pre operative Antibiotics

  • Cefazolin given before surgery to prevent a Staphylococcal skin infection of the surgical site

• Empiric

  • Confirm or suspected infection but organism is not known. Culture takes time and money.

  • This is the most common type of treatment we do.

  • And this is what we learnt till now.

  • But then, you should know the causative organisms for common infections.

  • E.g.,

    • Levofloxacin initiated for a patient with presumed community-acquired pneumonia

    • Ceftriaxone given for the treatment of suspected pyelonephritis

    • Vancomycin, tobramycin, and meropenem for a patient with probable

    • Hospital-acquired pneumonia in the intensive care unit

• Definitive

  • We know the organism and its sensitivity.

  • Choice is for safe, effective, cheap and narrowest spectrum possible

  • E.g.,

    • Transitioning from piperacillin/tazobactam to ampicillin in a patient with a wound infection caused by Enterococcus faecalis, which is susceptible to both drugs

    • Discontinuing ceftriaxone and initiating ciprofloxacin for a patient with a UTI caused by Klebsiella pneumoniae that is resistant to ceftriaxone but susceptible to ciprofloxacin

Take home messages

• Not every infection needs antibiotics

• If uncomplicated, start with narrowest spectrum

• If very serious patient, start with maximum but slowly de-escalate

• Overuse of Antibiotics is slowly making the world difficult to live…