1. Description of the problem

Principles of antimicrobial therapy

In patients suspected of being infected, the following elements of management should always be considered but may not all necessarily apply in all cases:

  • Supportive care, e.g., treat shock, hypoxia.

  • Antimicrobial therapy.

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  • Need for surgery – for diagnosis or therapy, e.g., drainage of abscess.

  • Community – is this contagious? What interventions are required to prevent spread within the community (ward, hospital, family, broader community)?

  • Prevention – e.g., immunization, antimicrobial chemoprophylaxis of contacts, care of vascular catheters.

This chapter addresses antimicrobial therapy.

The first set of decisions to be made:

  • Is an infection likely?

  • Where is it located? This usually provides the answer to the third and most important question:

  • What are the most likely causative organisms?

  • What are the likely antimicrobial susceptibilities of these organisms?

Initial management is empiric; to answer questions 3 and 4, one should use the following: (1) information from published studies of this infection; and (2) information from your specific unit.

Microbiologic information should be obtained from the patient to provide directed therapy. The most important principle in obtaining microbiological information is that specimens should be obtained from the site or presumed site of infection whenever possible. Blood cultures give information only about organisms in the blood.

The second decision to be made:

Given the answers to the first set of questions, what is the optimal agent to use?

This must take into account:

  • The necessary antimicrobial spectrum of the agent(s).

  • Pharmacokinetics.

  • Will it reach the site of the infection?

  • Adverse effects.

  • Drug-drug interactions.

  • Route of administration.

  • Cost (use the cheapest drug, other factors being equal).

The overriding principle is to use the narrowest spectrum agent possible for the clinical circumstance.

The susceptibilities of different bacteria to different antimicrobial agents are fairly predictable. However these susceptibilities vary over time and place. Therefore, it is important to know the susceptibilities of specific organisms in your hospital and unit.

Table I indicates commonly encountered/important microbial agents in the intensive care unit, and their usual susceptibilities.

Table II lists the organisms causing different types of infections at different sites in different types of hosts and suggested empiric therapy (i.e. the initial therapy based on the clinical and epidemiological information, prior to the availability of microbiological information). Once or if a specific agent is identified, therapy should be tailored accordingly.

Table I.n

Commonly encountered or important organisms and their usual antimicrobial susceptibilities

Table II.n

Microbial causes of infections according to site, and type of host, and recommended empiric antimicrobial therapy.

Table III lists the dosages, dosing intervals and routes of administration of antimicrobial agents by categories for children after the newborn period and for adults.

Table III.n

Dosages, dosing intervals, and routes of administration of antimicrobial agents, by categories, for children after the newborn period and adults.

Table IV lists the major adverse effects of antimicrobial agents.

Table IV:
Drug Adverse Reaction
Aminoglycosides Ototoxicity (auditory and vestibular), nephrotoxicity, potentiation of neuromuscular blockade
Carbapenems Seizures
Cephalosporins Allergy, rashes, Coombs positivity, prolonged PT/PTT, thrombocytopenia
   Ceftriaxone Gallbladder sludge; displacement of bilirubin from albumen;
do not administer with iv calcium
   Cefotaxime Photosensitivity
   Ceftazidime Photosensitivity
   Cefepime Allergy, diarrhea, neurotoxicity
   Cefazolin Allergy, elevated transaminases, decreased renal function, neutropenia, thrombocytopenia
Clindamycin Diarrhea, rash, potentiation of neuromuscular blockade
Daptomycin Myositis, eosinophilic pneumonia, peripheral neuropathy
Fluoroquinolones Dizziness, abdominal pain, photosensitivity, arthralgia, tendon rupture, interactions (especially Q-T interval prolongation; mental status changes (especially with non-steroidal drugs)
Linezolid Myelosuppression, peripheral and optic neuropathy (long-term usage), interactions, especially with serotoninergic agents
Macrolides Interactions (especially prolonged Q-Tc), gastrointestinal
   Erythromycin Upper abdominal discomfort, nausea/vomiting, diarrhea, cholestasis (estolate salt), dysrhythmia (iv), pyloric stenosis (neonate)
   Azithromycin Gastrointestinal, interactions
Metronidazole Metallic taste; disulfiram reaction; encephalopathy (prolonged usage)
Penicillins (most) Allergy, rashes, seizures (high dosages), interstitial nephritis, thrombocytopenia, neutropenia, eosinophilia, Coombs positivity, sodium excess
   Nafcillin Interaction with warfarin, increased transaminases
   Oxacillin Increased transaminases
   Piperacillin/tazobactam Coagulopathy (associated with renal failure)
Polymyxin/Colistin Nephrotoxicity, neurotoxicity, neuromuscular blockade
Rifampin Body fluid discoloration, interactions (very important), hepatotoxicity, thrombocytopenia, and “flu-like” symptoms when taken intermittently
Tetracyclines Diarrhea, bacterial overgrowth, photosensitivity, pseudotumor cerebri, hepatotoxicity, nephrotoxicity, vestibular disturbance (minocycline), dental staining (you must be alive to develop this!)
   Tigecycline Nausea/vomiting, diarrhea
Trim/sulfa* Allergy, Stevens-Johnson syndrome and other skin reactions, crystalluria, nephrotoxicity, bone-marrow suppression, hemolysis – with and without G6PD deficiency, hyperkalemia, bilirubin displacement (newborn)
Vancomycin Ototoxicity, nephrotoxicity, anaphylactoid reactions (“red man syndrome”)
   Isoniazid (INH) Hepatotoxicity, peripheral neuropathy, hypersensitivity
   Rifampin See above
   Pyrazinamide Hepatotoxicity, hyperuricemia, arthralgia
   Ethambutol Optic neuropathy
   Streptomycin Ototoxicity (hearing and vestibular), nephrotoxicity
   Ethionamide Gastrointestinal, hepatotoxicity, neurotoxicity, hypothyroidism
Amphotericin B Nephrotoxicity, hypokalemia, fever and chills, hypotension
Azoles Nausea, vomiting, drug-drug interactions, prolonged Q-Tc, hepatotoxicity
   Fluconazole Hepatotoxicity, interactions
   Voriconazole Hepatotoxicity, interactions, visual disturbance (transient after dose), fluorosis (prolonged usage)
   Posaconazole Adrenal insufficiency, nephrotoxicity, prolonged Q-Tc
   Itraconazole Nausea, vomiting, diarrhea, rash
Echinocandins Relatively free of adverse effects
   Micafungin Drug-drug interaction (sirolimus, nifedipine)
   Acyclovir Neurotoxicity, nephrotoxicity (crystalluria), neutropenia, phlebitis (iv)
   Cidofovir Nephrotoxicity
   Foscarnet Nephrotoxicity, electrolyte disturbances, especially of ionized calcium, magnesium and phosphorus, neurotoxicity, neutropenia
   Ganciclovir Neutropenia, thrombocytopenia, anemia, upper intestinal symptoms, mental status changes
   Oseltamivir Nausea, vomiting, diarrhea, skin reactions, behavioral changes
Antiretrovirals Interactions (very important), nausea, diarrhea, severe hypersensitivity – affecting skin and viscera, hepatotoxicity, hyperlipidemia, fat maldistribution
   Abacavir Severe hypersensitivity (test for HLA-B*5701)
   Atazanavir Indirect hyperbilirubinemia, 1st degree heart block, rash, hyperglycemia, nephrolithiasis, hyperlipidemia
   Darunavir Rash, hepatotoxicity, hyperglycemia, hyperlipidemia
   Dolutegravir Hypersensitivity, insomnia, headache
   Efavirenz Rash, psychologic disturbances, hepatotoxicity, ? teratogenic
   Emtricitabine Skin discoloration, exacerbation of liver disease when discontinued in individuals with hepatitis B
   Lamivudine Lactic acidosis, fever, cough, exacerbation of liver disease when discontinued in individuals with hepatitis B
   Nevirapine Hepatotoxicity, severe hypersensitivity reactions
   Raltegravir Rash, dizziness, insomnia, fever, rhabdomyolysis
   Tenofovir disoproxil fumarate Nephrotoxicity, decreased mineral bone density
   Zidovudine Anemia, neutropenia, lactic acidosis, myopathy, lipoatrophy
   Artemisinins Myelosuppression
   Artemether- lumefantrine Palpitations, arthralgia, myalgia, fatigue
   Artesunate Prolonged Q-Tc, dizziness, insomnia, hearing problems, anemia (3-4 weeks later)
   Atovaquone/proguanil Nausea, abdominal pain, headache, interactions, elevated transaminases
   Chloroquine Dizziness, nausea, vomiting, blurred vision, pruritus
   Quinidine Hypotension, dysrhythmias, including prolonged Q-Tc, diarrhea, interactions
   Quinine Cinchonism (tinnitus, visual disturbance, headache, nausea, abdominal pain), Hemolysis, deafness, photosensitivity IV: hypotension, hypoglycemia, dysrhythmias

Trim/sulfa = trimethoprim/sulfamethoxazole

2. Emergency Management


3. Diagnosis






Special considerations for nursing and allied health professionals.


What's the evidence?

Baltimore, RS, Gewitz, M, Baddour, LM. “Infective endocarditis in childhood: 2015 update. A scientific statement from the American Heart Association”. Circulation. vol. 132. 2015. pp. 1487-1515.

Green, M. “Introduction: Infections in solid organ transplantation”. Am J Transplant. vol. 13. 2013. pp. 3-8.

Fishman, JA. “Infection in Solid-Organ Transplant Recipients”. N Engl J Med. vol. 357. 2007. pp. 2601-14.

Jankelevich, S, Zeichner, SL, Read, JS. “Serious infections caused by typical bacteria”. Handbook of Pediatric HIV Care. 2006. pp. 653-73.

Lehrnbecher, T, Phillips, R, Alexander, S. “Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation”. J Clin Oncol. vol. 20. 2012. pp. 4427-4438.

Freifeld, AG, Bow, EJ, Sepkowitz, KA. “Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America”. Clin Infect Dis. vol. 52. 2011. pp. e56-e93.

Long, SS, Pickering, LK, Prober, CG. Principles and Practice of Pediatric Infectious Diseases. 2012.

Bennett, JE, Dolin, R, Blaser, MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 2015.

Red Book 2015 Report of the Committee on Infectious Diseases.

Bradley, JS, Nelson, JD. “Nelson's Pocket Book of Pediatric Antimicrobial Therapy”. 2016.

Gilbert, DN, Chambers, HF, Eliopoulos, GM, Saag, MS. The Sanford Guide to Antimicrobial Therapy 2015.