APPENDIX 2: Spectrum of Activity

A Note on Spectrum of Activity

Spectrum of activity is usually thought of as “does this drug cover this bug?” It is important to realize that this is a substantial oversimplification. A more accurate statement would be, “What is the probability, in this patient, that the pathogen I am concerned about is susceptible in vitro to this antibiotic?” The key components are “probability” and “in this patient.” Some antibiotics are always active against some organisms (e.g., penicillin and Streptococcus pyogenes) and a fair number of antibiotics are never active against some organisms at safe concentrations (e.g., vancomycin and Escherichia coli). But it is more common that there is some degree of variability in susceptibility across different isolates of the organism, and that there is variability in this variability! For example, Table A–1 describes the susceptibility of E. coli to ciprofloxacin at three hospitals—Major Medical Center, Trauma Hospital, and the Regional Children’s Hospital—all located in the same city (this example is based on actual data, but the names have been changed to protect the “innocent” institutions).

TABLE A–1 Susceptibility of E. coli to Ciprofloxacin at Three Hospitals

One key aspect of variability is time: you can see that in 1998, ciprofloxacin had excellent activity against E. coli isolated from inpatients at Major Medical Center. Over the next decade, its activity declined sharply. So it is important to keep “when” in perspective when reading the literature about spectrum of activity; sadly, the general trend is for susceptibility to decrease over time.

Another aspect of variability is “where.” Trauma Hospital is just on the other side of town from Major Medical Center, but among patients there, ciprofloxacin is much more active. There can be substantial geographic variability in susceptibility in different countries, states, regions, and even, as illustrated here, within a city. Although the variability in this case is most related to the last consideration, “who,” as illustrated by the excellent activity of ciprofloxacin against E. coli among patients at the Regional Children’s Hospital. Regional Children’s Hospital is located within the Major Medical Center, so it is not a matter of geography per se. Those patients are less likely to be exposed to fluoroquinolones and thus less likely to develop and spread resistant organisms to each other. So to best answer the question, “Does ciprofloxacin cover E. coli in this city?”, you want to know when the data were collected, where the patient acquired the infection, and who the patient is (in terms of risk factors for resistance).

With that caution, no one can hold all of the different percentage susceptibilities for different drug–bug combinations in their heads, so learning general patterns of susceptibility is the first step. Tables A–2 and A–3 represent the usual (average across most areas and patient populations), clinically useful (not just good in the test tube) spectrum of activity for antibiotics and antifungal for empiric use.

TABLE A–2 Clinically Useful Spectra of Activity for Empiric Antibiotic

Selection

Key: ++ = good activity; + = some activity; +/− = variable activity

*Anerobes here include GI anerobes except Clostridium difficile, for which the only antibiotics with good clinical activity on this list are vancomycin and metronidazole.

†Aminoglycosides have useful synergistic activity versus Gram-positive cocci only when paired with a cell-wall active agent (e.g., beta-lactams, vancomycin).

Abbreviations: MSSA = methicillin-sensitive Staphylococcus aureus; MRSA = methicillin-resistant

Staphylococcus aureus; Strep = streptococci; GNR = aerobic Gram-negative rods (in general, and not including Pseudomonas aeruginosa); Pseudo = Pseudomonas aeruginosa; Imi/Mero/Dori=imipenem, meropenem, doripenem; Gent/Tobra=gentamicin, tobramycin; Amp/Sulb = ampicillin/sulbactam; Pip/Tazo = piperacillin/tazobactam; Quin/Dalf = quinupristin/dalfopristin; TMP/SMX = trimethoprim/sulfamethoxazole.

TABLE A–3 Clinically Useful Spectra of Activity for Empiric Antifungal

Selection

Key: ++ = good activity; + = some activity; +/− = variable activity

Abbreviation: Anidula/Caspo/Mica = anidulafungin, caspofungin, micafungin.