Antibiotics Cheat Sheet

Introduction

While the selection of empirical antimicrobial therapy is highly subjective, depending on the patient's clinical condition (as reflected in antibiotic guidelines based on clinical indication) and ultimately guided by culture and sensitivity results, many pharmacists desire fundamental guidance on the typical applications of antimicrobials and those reserved for highly resistant bacteria.

  • This article is written to meet this demand, acknowledging that it does not offer a complete picture of antimicrobial selection.

Nonetheless, antimicrobials should always be modified based on results of culture and sensitive testing to definitive therapy agent(s) that have the narrowest spectrum possible.

  • In many cases, shorter durations of therapy have been shown to be as effective as traditionally longer courses.
  • As many oral agents have excellent bioavailability, switching from parenteral to oral therapy wherever possible is recommended.



Penicillins

Narrow spectrum penicillins are mainly active gram-positive bacteria (e.g. streptococcal, pneumococcal, gonococcal and meningococcal infections), but are inactivated by beta-lactamase enzymes.

  • Benzylpenicillin sodium (penicillin G) is inactivated by gastric acid and absorption from the GIT is low; therefore it must be given by injection.
  • Phenoxymethylpenicillin (Penicillin V) has a similar antibacterial spectrum to benzylpenicillin sodium, but is less active. It should not be used for serious infections because absorption can be unpredictable and plasma concentrations variable.
  • Benzathine benzylpenicillin is used for the treatment of early syphilis and late latent syphilis; it is given by intramuscular injection.

Moderate-spectrum penicllins: amoxicillin and ampicillin have better activity than benzylpenicillin against some gram-negative bacteria (e.g. Escherichia coli, Haemophilus influenzae), but are inactivated by strains that produce beta-lactamase enzymes.

  • They are the drugs of choice for susceptible enterococcal infections.
  • When given parenterally, amoxicillin and ampicillin are equivalent. However, amoxicillin is better absorbed than ampicillin when given by mouth, producing higher plasma and tissue concentrations.

Most Staphylococcus aureus strains produce beta-lactamase enzymes, and isolates should only be considered penicillin-susceptible if susceptibility is confirmed by a clinical microbiologist.

  • Dicloxacillin and flucloxacillin are narrow-spectrum penicillins with antistaphylococcal activity (i.e. stable to beta lactamase enzymes produced by staphylococci, such as penicillin-resistant and MSSA). They are recommended as first-line treatment for many skin and soft tissue infections.

The beta-lactamase enzyme inhibitors, clavulanate and tazobactam, have little inherent antibacterial activity; they inhibit the beta-lactamase enzymes produced by Staphylococcus aureus, Bacteroides fragilis and Haemophilus influenzae, and some of the beta-lactamase enzymes produced by Escherichia coli and Klebsiella species.

  • They are used in combination with amoxicillin (clavulanate) or piperacillin (tazobactam) to significantly broaden the spectrum of activity of these antibiotics.
  • Piperacillin and tazobactam have a broad spectrum of activity against a range of Gram-positive and Gram negative bacteria and anaerobes (i.e. not requiring metronidazole). They are active against Pseudomonas aeruginosa, but not MRSA.



Cephalosporins

Cefalexin and cefazolin have a similar moderate spectrum of antibacterial activity. In terms of gram-positive activity, they are active against streptococci and staphylococci, including beta-lactamase–producing (penicillin-resistant) staphylococci, but inactive against methicillin-resistant Staphylococcus aureus (MRSA), enterococci and Listeria monocytogenes.

  • Cefazolin is the preferred drug for the majority of procedures that require prophylaxis.

Cefuroxime and cefaclor are moderate-spectrum cephalosporins with anti-Haemophilus influenza activity and marginally broader gram-negative activity.

  • Cefuroxime has replaced cefaclor in guidelines because cefaclor has inferior activity against Streptococcus pneumoniae and is more likely to cause serum sickness-like syndrome, particularly in children.

Cefotaxime, ceftazidime and ceftriaxone are "third generation" cephalosporins with greater activity than the "second generation" cephalosporins against certain Gram-negative bacteria.

  • However, they are less active than cefuroxime against Gram-positive bacteria, most notably Staphylococcus aureus.
  • In adults, ceftriaxone is usually preferred to cefotaxime because it requires less frequent dosing due to longer half-life.
  • Ceftriaxone are contraindicated in patients younger than 6 to 8 weeks of age due to their displacement of bilirubin from protein-binding sites and potential for kernicterus.
  • Ceftazidime has good activity against pseudomonas.

The fourth-generation cephalosporin cefepime has excellent aerobic gram-negative coverage, including Pseudomonas aeruginosa and other bacteria producing AmpC B-lactamases. Its gram-positive activity is similar to that of ceftriaxone.

  • It is routinely used for empiric therapy in febrile neutropenic patients.

Ceftaroline is a "fifth generation" cephalosporin with bactericidal activity similar to cefotaxime, but has an extended spectrum of activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and multi-drug resistant Streptococcus pneumoniae.



Carbapenems

Carbapenems are broad-spectrum antibacterial drugs with activity against many strains of gram-negative bacteria that are resistant to other drug classes. However, carbapenem resistance is emerging worldwide, often due to the production of various carbapenemase enzymes.

  • They are inactive against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Enterococcus faecium, Mycoplasma species, Chlamydia species and Stenotrophomonas maltophilia.
  • Meropenem has less seizure-inducing potential than imipenem with cilastatin and can be used to treat central nervous system infection.
  • Unlike the other carbapenems, ertapenem has poor activity against Pseudomonas aeuroginosa, Enterococcus faecalis and Acinetobacter species.


Monobactams

Aztreonam is a monocyclic beta-lactam (monobactam) antibiotic with an antibacterial spectrum limited to Gram-negative aerobic bacteria including Pseudomonas aeruginosa, Neisseria meningitidis and Haemophilus influenza.

  • It should not be used alone for "blind" treatment since it is not active against Gram-positive organisms.
  • The monobactam structure makes cross-reactivity with a beta-lactam unlikely, therefore aztreonam is primarily used when a beta-lactam allergy is present.



Aminoglycosides

All aminoglycosides (amikacin, gentamicin, neomycin sulfate, streptomycin and tobramycin) are bactericidal and active against some Gram-positive and many Gram-negative organisms.

  • Amikacin, gentamicin and tobramycin are also active against Pseudomonas aeruginosa.
  • Streptomycin is active against Mycobacterium tuberculosis and is now almost entirely reserved for tuberculosis.

Gentamicin is active against most aerobic gram-negative bacteria, including Pseudomonas aeruginosa, but is inactive against anaerobes and has poor activity against haemolytic streptococci and pneumococci.

Amikacin is more resistant to bacterial enzymatic inactivation than gentamicin or tobramycin, so it should generally be reserved for treating infections resistant to other aminoglycosides.

Nephrotoxicity and ototoxicity are the major adverse effects of aminoglycosides.

  • Concomitant administration of aminoglycosides with other known nephrotoxic agents should be avoided if possible.
  • If possible, avoid ear drops containing framycetin or neomycin in patients with a perforated tympanic membrane or a tympanostomy tube in situ because of the risk of inner ear damage; however, this complication appears to be rare.



Quinolones

Quinolones should generally be reserved for treatment of infections resistant to other drugs or when alternative antibiotics are contraindicated, since fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions (e.g. tendinitis and tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy and CNS effects)

  • Ciprofloxacin is active against both aerobic Gram-positive and Gram-negative bacteria, including Salmonella, Shigella, Campyblobacter, Neisseria and Pseudomonas. Most anaerobic organisms are not susceptible.
  • Moxifloxacin, an extended-spectrum quinolone, has increased activity against gram-positive aerobic bacteria (including staphylococci and streptococci) compared to ciprofloxacin.
  • Norfloxacin is reserved mainly for multidrug-resistant cystitis, provided the pathogen is susceptible.

Resistance to quinolones is now widespread, particularly in Enterobacterales (enteric gram-negative bacilli), Pseudomonas aeruginosa, Campylobacter species and Neisseria gonorrhoeae.



Macrolides

The macrolides have an antibacterial spectrum that is similar but not identical to that of penicillin; they are thus an alternative in penicillin-allergic patients.

  • Clarithromycin is also used in combination with other drugs for nontuberculous mycobacteria (including Mycobacterium avium complex) and eradication of Helicobacter pylori.
  • Azithromycin is less active than erythromycin against gram-positive bacteria but has a broader range of gram-negative activity (e.g. Salmonella species and Haemophilus influenzae). Azithromycin is also active against nontuberculous mycobacteria (including MAC), Rickettsia species and some parasites (e.g. Toxoplasma gondii).

Azithromycin, erythromycin and clarithromycin can prolong the QT interval.

Erythromycin and clarithromycin are potent inhibitors of the cytochrome P450 enzyme CYP3A4, so they have many clinically significant drug interactions.



Tetracyclines

The tetracyclines are broad spectrum antibiotics whose value has decreased owing to increasing bacterial resistance.

  • However, they remain the treatment of choice for infections caused by Chlamydia species, Rickettsia species, Mycoplasma species, spirochaetes, some nontuberculous mycobacteria and some protozoa (e.g. Plasmodium species causing malaria).
  • Minocycline has a broader spectrum than other tetracyclines (e.g. doxycycline), but adverse effects (e.g. benign intracranial hypertension, vestibular adverse effects, skin pigmentation) limit its use.
  • Tetracyclines have many clinically significant drug interactions, such as antacids.
  • Photosensitivity reactions can occur with tetracyclines; warn patients to avoid sun exposure.



Sulfonamides and Trimethoprim

This class of antibiotics (sulfadiazine, sulfamethoxazole and trimethoprim) are most commonly used for uncomplicated UTIs, sinusitis and otitis media.

  • Because of its mechanism of action, trimethoprim can interfere with folate metabolism, and high doses or prolonged treatment may result in megaloblastic changes (e.g. macrocytic anaemia, mild thrombocytopenia, leucopenia). Folate supplementation may be considered.
  • Trimethoprim also inhibits tubular excretion of potassium and can cause hyperkalaemia.

The combination of trimethoprim+sulfamethoxazole (cotrimoxazole) should be restricted to indications for which the combination is more effective than trimethoprim alone.

Avoid trimethoprim+sulfamethoxazole in neonates (up to 28 days old) because of the risk of kernicterus (precipitated by the displacement of bilirubin from albumin by sulfonamides).

Some patients are hypersensitive to sulfonamide antibiotics.



Vancomycin

The glycopeptide vancomycin has bactericidal activity against a wide range of aerobic and anaerobic Gram-positive bacteria; gram-negative bacteria are not susceptible.

  • The primary indication for parenteral glycopeptides is treatment of infection with methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphylococci (e.g. Staphylococcus epidermidis) and Enterococcus faecium.
  • Glycopeptides are sometimes used for prophylaxis of these infections.

Oral vancomycin is used to treat Clostridioides difficile (formerly known as Clostridium difficile) infection.

  • In patients with severe disease, particularly in the presence of ileus, vancomycin can be given as a retention enema in addition to oral therapy.



Oxazolidinones

Linezolid is inactive against Gram-negative organisms; active primarily against Gram-positive organisms such as staphylococci (including MRSA), streptococci (including penicillin-resistant Streptococcus pneumoniae) and vancomycin-resistant Enterococci (VRE), hence should be reserved for infections caused by multidrug-resistant bacteria.

  • Myelosuppression is reversible, and includes anaemia (common), thrombocytopenia, leukopenia, neutropenia, rarely pancytopenia; occurs particularly in people treated for >10-14 days or with risk factors.
  • Linezolid inhibits mitochondrial protein synthesis, which is thought to result in adverse effects such as optic and peripheral neuropathy, anaemia and lactic acidosis. These usually resolve after stopping linezolid, but there may be permanent damage, e.g. blindness. Long courses of treatment, particularly >28 days, increase the risk as may some mitochondrial DNA mutations.
  • Linezolid is a weak monoamine oxidase inhibitor, so may interact with some foods and drugs.



Polymyxins

Polymyxins are polypeptide antibiotics used to treat MDR gram negative organisms such as carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA).
  • Conversely, some organisms are intrinsically or naturally resistant to polymyxins (Serratia spp., Proteus spp., Providencia spp., Morganella spp., Burkholderia cepacia).
Polymyxins are hydrophilic drugs that have concentration-dependent with time-dependent kill characteristics.
  • Both polymyxin E (Colistin) and Polymyxin B have the same spectrum of activity but their difference is mainly attributed to the fact that Polymyxin B is administered in its active form whilst Polymyxin E (Colistin) is administered as an inactive prodrug.
  • Besides that, Polymyxin E (Colistin) requires dose adjustment for renal impairment whilst Polymyxin B does not.



Lincosamides

Lincosamides are active against most gram-positive aerobic bacteria (such as staphylococci, streptococci, but not Enterococcus species), most anaerobes (including Bacteroides fragilis) and some protozoa (e.g. Toxoplasma gondii).

  • Despite limited clinical evidence, lincosamides are used to reduce bacterial toxin production in necrotising skin and soft tissue infections and toxic shock syndromes.
  • Clindamycin may be active against Cutibacterium acnes (formerly Propionibacterium acnes).

Clindamycin and lincomycin have similar adverse effects; they can both cause antibiotic-associated diarrhoea.



Metronidazole

Metronidazole is an antimicrobial drug with high activity against anaerobic bacteria and protozoa (including Trichomonas vaginalis, Giardia intestinalis and Entamoeba histolytica).

  • Metronidazole may cause nausea, vomiting, flushing, headache and palpitations if taken concomitantly with alcohol.



Rifamycins

Rifampicin and rifabutin are active against gram-positive bacteria (including staphylococci), gram-negative bacteria and mycobacteria.

  • These drugs must always be used in combination with antimicrobials from a different class because of the rapid emergence of resistance.
  • Rifampicin is mainly used for the treatment of tuberculosis, nontuberculous mycobacteria (including MAC) and methicillin-resistant Staphylococcus aureus (MRSA) infection. Rifampicin is also used as prophylaxis in contacts of patients with Haemophilus influenzae type b infection and meningococcal disease.
  • Rifampicin and rifabutin have many clinically significant drug interactions.



Urinary Agents

Nitrofurantoin is active against bacteria that commonly cause cystitis, including many gram-negative bacilli (e.g. Escherichia coli) and gram-positive cocci (e.g. Enterococcus faecalis).

Fosfomycin has activity against many strains of multidrug-resistant gram-negative bacteria, including isolates that produce extended-spectrum beta-lactamase enzymes (ESBLs), but is inactive against Pseudomonas aeruginosa.



Miscellaneous

Daptomycin is a lipopeptide antibacterial with a spectrum of activity similar to vancomycin, but its efficacy against enterococci has not been established.

Sodium fusidate is a narrow-spectrum antibiotic, mainly active against Staphylococcus aureus.

  • It should always be used in combination with other antibiotics because resistance develops readily.

Sulbactam component of 9 g is required for Acinetobacter baumanii.

Topical mupirocin is effective for bacterial skin infections, particularly those caused by Gram-positive organisms, except pseudomonal infection.

  • Prolonged or widespread use causes high-level mupirocin resistance in methicillin-resistant Staphylococcus aureus (MRSA).



Summary

Gram Stain

Bacterial organisms

  • Gram-positive
    • Streptococcal, Pneumococcal, Gonococcal and Meningococcal infections - consider Benzylpenicillin, phenoxymethylpenicillin, ampicillin and amoxicillin, but these drugs are inactivated by beta-lactamase (common in staphylococcus aureus)
    • Methicillin-susceptible Staphylococcus aureus (MSSA) - consider dicloxacillin, flucloxacillin, 1st/2nd generation cephalosporins, amoxicillin with clavulanate.
    • Methicillin-resistant Staphylococcus aureus (MRSA) - consider vancomycin, daptomycin, linezolid, ceftaroline
    • Vancomycin-resistant Enterococci (VRE) - consider linezolid, daptomycin
    • Clostridium difficile - consider oral vancomycin, metronidazole
  • Gram-negative
    • Aerobic (e.g. HNPEK: Haemophilus, Neisseria, Proteus, E. coli, Klebsiella, and CAPES: Citrobacter, Acinetobacter, Providencia, Serratia) - consider aminoglycosides, piperacillin/tazobactam, cefepime, carbapenems
    • Acinetobacter baumanii - consider sulbactam
    • Pseudomonas aeruginosa - consider piperacillin/tazobactam, cefepime, ceftazidime, carbapenems (except ertapenem), aztreonam
    • Carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) - consider polymyxins
  • Anaerobes
    • Consider metronidazole, lincosamides (e.g. clindamycin), carbapenem
  • Atypical
    • Chlamydia spp., Legionella spp., Mycoplasma pneumoniae - consider macrolides, tetracyclines, quinolones
    • Mycobacterium tuberculosis - consider rifamycins
  • Urinary tract pathogens
    • Consider trimethoprim, nitrofurantoin, fosfomycin (also effective against some ESBL-producing organisms)

Commonly Used Antibiotics for Specific Pathogens



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