Bactericidal effects of antibiotics on slowly growing and nongrowing bacteria

TLDR

Antimicrobial agents are typically tested on rapidly dividing bacteria, yet in infections bacteria often grow slowly, and the clinical significance of reduced killing under these conditions remains unclear. The study examined how various antibiotic classes affect gram‑positive and gram‑negative bacteria during nongrowing and slowly growing phases. The authors evaluated the bactericidal activity of several antibiotic classes against gram‑positive and gram‑negative bacteria in nongrowing and slowly growing states. Only ciprofloxacin and ofloxacin killed nongrowing gram‑negative bacteria, and no antibiotic achieved 3‑order‑of‑magnitude killing of Staphylococcus aureus; for very slowly growing gram‑negative bacteria, gentamicin, imipenem, meropenem, ciprofloxacin, and ofloxacin were up to 5.7 orders of magnitude more lethal than piperacillin or cefot.

Abstract

Antimicrobial agents are most often tested against bacteria in the log phase of multiplication to produce the maximum bactericidal effect. In an infection, bacteria may multiply less optimally. We examined the effects of several classes of antimicrobial agents to determine their actions on gram-positive and gram-negative bacteria during nongrowing and slowly growing phases. Only ciprofloxacin and ofloxacin exhibited bactericidal activity against nongrowing gram-negative bacteria, and no antibiotics were bactericidal (3-order-of-magnitude killing) against Staphylococcus aureus. For the very slowly growing gram-negative bacteria studied, gentamicin (an aminoglycoside), imipenem (a carbapenem), meropenem (a carbapenem), ciprofloxacin (a fluoroquinolone), and ofloxacin (a fluoroquinolone) exhibited up to 5.7 orders of magnitude more killing than piperacillin or cefotaxime. This is in contrast to optimally growing bacteria, in which a wide variety of antibiotic classes produced 99.9% killing. For the gram-positive and gram-negative bacteria we examined, antibiotic killing was greatly dependent on the growth rate. The clinical implications of slow killing by chemotherapeutic agents for established bacterial infections and infections involving foreign bodies are unknown.