Antimicrobials: Cell Wall Inhibitors Flashcards by Denisse Tiangco

The only anti tb medication that is bacteristatic

Ethambutol

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Genetic material in bacteria that confers antibiotic resistance

Plasmids

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Bactericidal

Kills bacteria
Cell wall synthesis inhibitors
Narrow spectrum

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Bacteriostatic

Inhibits growth
Protein synthesis
Broad spec

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Methicilin causes

Interstitial nephritis

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doc for atypical pneumonia

Macrolide (Erythromycin)

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DOC for all stages of syphilis

Penicillin

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Penicillin interferes with the last step of bacterial cell wall synthesis:

Transpeptidase

transpeptidation or cross-linking of peptidoglycan chains

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Beta lactam attached to thiazolidine ring

Penicillin

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Nucleus of penicillin

aminopenicillanic acid

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Penicllin can only penetrate meninges if they are

inflamed

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enzyme responsible for peptidoglycan cross-linking which is the final step in cell wall synthesis

Transpeptidase

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Only oral pen

Pen V

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thin walled

Gram negative

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Most common cause of atypical pneumoniae

M pneumoniae

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DOC for M pneumoniae

Macrolide:

Erythromycin

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Given IV because not effective orally due to poor absorption from the intestinal tract

Oral doses must be very large

Pen G (benzyl penicillin)

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Repository form of Pen G due to rapid elimination from blood stream

Pen G Procaine

Pen G Benzanthine

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Pen G Notorious for hypersensitivity

Cross allergenecity
Anaphylaxis

Penicillin G Procaine

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Acid stable penicillin

Penicillin V (phenoxymethylpenicillin)

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Drug of choice for all stages of syphyllis

Penicillin

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Prototype drug of Penicillase-resistant Penicillin/Antistaphylococcal Penicllin but off the market due to high incidence of interstitial nephritis

Methicillin (2.6 dimethoxyphenylpenicillin)

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Methicillin causes

interstitial nephritis

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Penicllin SE

Seizure - renal problem or newborn
Hypersensitivity 
Diarrhea
Hemolytic anemia
Hypernatremia 
Hyperkalemia

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Antistaph Penicillin

``` Methicillin Nafcillin Oxacillin Dicloxacillin Cloxacillin ```

Adverse effect of antistaphylococcus penicillin

granulocytopenia

Small amounts excreted in kidneys and majority in the bile hence can be given in patients with renal problems

Nafcilin (2-ethoxy-l-phenylpenicillin)

Isoxazolyl penicillins | best absorbed

Oxacillin Cloxacillin Dicloxacillin

Have antibacterial spectrum similar to pen G but are more effective against gram negative bacilli

Aminopenicillin Ampicillin Amoxicillin

Poor GI absorption | More frequent Parenterally

Ampicillin

Better GI absorption aminopenicillin

Amoxicillin

Ampicillin is notorious for

Pseudomembranous colitis

``` Helps kill enterococci Haemophilis E coli Listeria Proteus Salmonella Enterococci ```

Ampicillin

Prodrug of ampicillin

Hetacillin Bacampicillin Cyclacillin

If patient is allergic to penicillin you may give

Erythromycin

Unstable in gastric acid hence given IM/IV

Antipseudomonal penicillins

Antipseudomonal penicillin

``` Mezlocillin Piperacillin Azlocillin Carbenicillin Ticarcillin ```

For gram negative esp Pseudomonas except Klebsiella nosocomial infections

Antipseudomonal Penicillin

Ticarcillin/Carbenicillin is known to cause

Platelet dysfunction use cautiously in septic patients

Carboxypenicillin

Carbenicillin | Ticarcillin

Most potent ureidopenicillin

Piperacillin

Ureidopenicillin

Piperacillin Azlocillin Mezlocillin

Structurally related to the beta lactam ring of penicillin but do not have significant antibacterial activity Instead, they bind to and inactivate beta lactamases

Beta lactamase inhibitors Clavulanic acid Sulbactam Tazobactam

Prevent bacteria from destroying amoxicillin

Clavulanic acid

Acid resistant penicillin

``` V Pen Oxacillin Dicloxacillin K (c) Cloxacillin Amoxicillin/Ampicillin ``` VODKA

Penicillinase resistant penicillin

``` Cloxacillin Oxacillin Nafcillin Dicloxacillin Oxacillin Methicillin ``` CONDOM

Penicillin SE

``` Abdominal pain/Anaphylaxis Black tongue Diarrhea Skin rash Stomach upset Seizure ``` ABCDSSS

Beta lactam attached to dihydrothiazine ring

Cephalosporin 5-10% cross reactivity with penicillin

Nucleus of cephalosporin

7 Amino Cephalosporanic acid

cephalosporins are known for this SE

Nephrotoxicity | Disulfiram like effects with ETOH

First to third gen cephalosporins have

dec in gram positive coverage inc in gram negative coverage inc in CNS penetration inc in beta lactamase

First gen cephalosporins can be

Pen G substitutes

Resistant to staphylococcal penicillinase Inferior activity against Gram positive Enhanced activity against Gram negativd

Second gen cephalosporin

3rd Gen Cephalosporins

``` Cefotaxime Ceftriaxone Cefixime Ceftazidime Cefbuten Cefoperazone ```

DOC for meningitis

Ceftriaxone | Cefotaxime

3rd Gen active against P aeruginosa

Ceftazidime also Cefoperazone

Fourth gen Cephalosporin

Enhanced activity against gram positive and gram negative, pseudomonas Ex: cefipime

1st Gen Cephalosporin

``` Cefalexin Cefazolin Cefadroxil Cephapirin Cephradine ```

2nd Gen Cephalosporin

``` Cefuroxime Cefoxitin Cefaclor Cefamandole Cefpodoxime Cefprozil ```

3rd Gen Cephalosporin

``` Ceftriaxone Cefotaxime Ceftazidime (Tazicef, Tazidime) Ceftibuten Cefoperazone ```

4th Gen Cephalosporin

Cefipime | Cefpirome

Lab work for cephalosporin

Creatinine due to risk for nephrotoxicity

Metronidazole also has this effect | Sulfonylureas

Nephrotoxicity | Disulfiram-like reaction

Serious Klebsiella infections For patients with mild allergy Coverage: Proteus, E coli, Klebsiella (UTI)

1st Gen Cephalosporin PEK

Coverage: ``` H influenzae Enterobacter aerogenes Neisseria species Sereatia marcenses + PEK ```

2nd Gen Cephalosporin HENPEKS

For otitis media and sinusitis

Cefaclor

For mixed aerobic and anaerobic infections

Cefoxitin

CAP

Cefuroxime

Causative agent for: Cherry red colonies UTI Red diaper syndrome

Serratia marcenses

Penetrates CSF (DOC Meningitis) Sepsis of unknown organism Empiric therapy of life threatening conditions Inferior against gram positive but has enhanced activity against gram negative

3rd Gen Cephalosporin

Administration of vaccines against these organisms dec severity of COVID

H influenza | PCV

Empiric therapy in febrile neutropenic patients | UTI, pneumonia, skin infections

4th Generation Cephalosporin

Best penetrates BBB

Ceftriaxone

MRSA VRSA Acute bacterial skin infection, CAP

5th Gen Cephalosporin Ceftaroline Ceftobiprole

Anti pseudomonal coverage

Ceftazidime

Renal dihydropeptidase inhibitor

Cilastin

Broadest in activity Resistant to beta lactamase Inactivated by dihydropeptidase in the kidney

Carbapenem

Undergoes cleavage by dihydropeptidase

Imipenem

Dihydropeptidase is inhibited in the brushborder of the proximal tubule by

Cilastin

Imipinem | Carbapenem SE

Seizure | GI effect

The beta lactam ring is not fused to another ring Resembles aminoglycosides but does not cause ototoxicity and nephrotoxicity Preserved Gram positive and anaerobic flora activity Active against Gentamycin resistant organism No cross allergenicity with Penicillin

Monobactam

Bactericidal | Active against Gram negative organisms including Enterobacter and P aeruginosa

Aztreonam

Intraabdominal infections | Septicemia

Aztreonam

Empiric therapy | Severe infection caused by drug resistant organisms

Ertapenem

Anti pseudomonas coverage

Meropenem | Aztreonam

Clinical use has been limited by their undesirable side reactions especially renal toxicity Lack systemic activity hence only used topically except Vancomycin used for systemic infections

Polypeptide

Mild clostridi dificille (pseudomembranous colitis) infection DOC

Metronidazole

Moderate to Severe Clostridium dificille

Vancomycin

Glycopeptide active against Gram positive and MRSA From streptomyces orientalis Slow IV infusion employed for treatment of systemic infections

Vancomycin

Vancomycin AE

Red Man Syndrome

Vancomycin binds to the

D-alanyl-D-alanine portion DADA of cell wall inhibiting peptidoglycan polymerization

Vancomycin causes

Ototoxicity and hypersensitivity

Vancomycin also causes the notorious

Red Man Syndrome

Rate dependent infusion reaction (and not a true allergic reaction) involving ``` Flushing Erythema Pruritus Affects upper body, neck and face > lower body Myalgia, dyspnea, hypotension ``` Mx: Stop infusion Administer diphenhydramine Can restart at slower rate once symptoms resolve

Red Man Syndrome

Vancomycin causes Red Man Syndrome because it directly activates

Mast cells causing histamine release

Cyclic peptide or mixture of a polypeptide from Bacillus subtilis Blocks transfer of peptidoglycan unit to growing cell wall Poorly absorbed Active against a wide variety of Gram + organisms Limited to topical use due to toxicity

Bacitracin

Made from bacillus polymyxa Effective primarily against gram positive organisms Alterates cell membrane permeability of bacteria and fungi

Polymyxin Polymyxin B Colistin (Polymyxin E)

Useful against gram negative organisms | From Bacillus brevis

Gramicidin

Organisms without cell wall or not actively growing are not susceptible to

Penicillin | ex Mycoplasma

Pen AE

Hypersensitivity Seizure Diarrhea Hemolytic anemia

Hypersensitivity to penicillins:

Cross allergenecity | Anaphylaxis

For staph thay produces penicillinase | AE

granulocytopenia

Methillin AE

interstitial nephritis

Antipseudomonal Pens are given IV/IM because

unstable in gastric acid

For gram negative bacilli esp Pseudomonas EXCEPT Klebsiella Ticarcillin/carbenicillin SE

platelet dysfunction | careful in septic

Ampicillin Amoxicillin coverage

``` Enterococci HELPS Haemophilus E coli Listeria Proteus Salmonella Enterococci ```

5th Gen Cephalosporin

Ceftaroline | Ceftobiprole

Ceftolozane + Tazobactam

Zerbaxa

Disulfiram reactions

Cephalosporin (cefotetan and cefoperazone) Sulfonylurea (Chlorpropamide) Griseofulvin Metronidazole Procarbazine

Beta lactamase resistance to B lactam antibiotics such as Pen, Ceph, Carba inhibitors

Clavulanic acid (Co-Amox) Sulbactam (Ampi-sul) Tazobactam (PipTaz)

Prevenrs bacteria from destroying amoxicillin Beta lactamase inhibitor

Clavulanic acid

Beta lactamase producing organisms

``` S aureus H influenzae Neisseria Moraxella Legionella ```

Monobactam resistant to beta lactamase Inhibits cell wall synthesis Synergistic with aminoglycoside No cross allergenecity with penicillin

Aztreonam - Monobactam

Allergy to Linezolid give Also renal failure cannot give Vanco

Daptomycin Pen - Erythro - Vanco - Linezolid

Advantages of Aztreonam

Resembles aminoglycosides but does not cause Ototoxicity and Nephrotoxicity Preserve G+ and anaerobic flora Active against Gentamicin-resistant organism No cross allerginicity with Penicillin

Antineoplastic Ototoxicity and Nephrotoxicity

Cisplatin | Aminoglycoside

Beta lactam that binds to penicillin binding proteins Broadesr activity Severe infections causes by drug resistant organisms

Carbapenem Imipenem Meropenem Ertapenem

Inactivates carbapenem in proximal tubules of kidneys

Dihydropeptidase enzyme

Inhibits dihydropeptidase enzyme

Cilastin combined with Imipenem for polongation

Vacomycin inhibition on D-Ala-D-Ala

Transglycosylation | Transpeptidation

Red Man’s Syndrome

``` Nicotinic acid Niacin Nifedipine Amphotericin Vancomycin ``` NNNAV

Bacitracin SE

Nephrotoxicity (hematuria, proteinuria, Na retention) | Hypersensitivity

Analog of D alanine Cell wall synthesis inhibitor 2nd line for Tuberculosis

Cycloserine

Polymyxin hyperpigmentation is caused by

Melanocyte Stimulating Hormone MSH