Ciprofloxacin, a broad-spectrum antimicrobial drug, has been extensively used in inpatient and outpatient settings. The probability of cure of an infection has been shown to be dependent on the 24 h area under the curve (AUC) of ciprofloxacin and the minimal inhibitory concentration (MIC) for specific bacteria [1–5]. The quotient AUC : MIC needed for a high probability of cure varies in different studies. AUC : MIC > 125 was found to be predictive of microbiological and clinical cure in patients with serious Gram-negative infections and in Intensive Care Unit (ICU) patients [3, 5]. Microbiological cure was reached in 86% above and in 26% below this breakpoint and clinical cure in 82% above and in 42% below this breakpoint . Using a clinical outcome-based Monte Carlo simulation, it was shown that in patients with Enterobacteriaceae bacteraemia an AUC : MIC > 250 was associated with cure rates of 91% in patients with values above and of 29% below this breakpoint . Moreover in nosocomial pneumonia dose alterations based on plasma drug concentration and bacterial MIC value improved the probability of good clinical outcome and pathogen eradication .
In the nineties, it was shown that 80% of treatment failures during ciprofloxacin treatment were due to drug resistance . The MIC predicted clinical response, especially in patients with infections caused by organisms for which the MICs were at the marginal points of susceptibility. Development of resistance to ciprofloxacin was largely confined to marginally susceptible organisms such as Staphylococcus aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa. Recently Enterobacteriaceae were added to this marginally susceptible group based on a Monte Carlo simulation . Both MIC and resistance for ciprofloxacin are steadily increasing. In the Netherlands ciprofloxacin resistance increased from 1 to 15% in Escherichia coli and from 1 to 13% in Klebsiella pneumoniae from 2001 until 2009, and in susceptible bacteria MICs increased [8, 9]. In Greece ciprofloxacin resistance for E. coli increased from 9% in 2001 to 23% in 2009 and ciprofloxacin resistance for K. pneumoniae increased from 54% to 66% from 2005 to 2009% .
With increasing MICs, the targeted AUC : MIC > 125 may be less often reached, resulting in increasing ciprofloxacin resistance and higher clinical failure rates. Indeed, Perreiter et al. calculated with a population model from the literature that 66% reached the minimum AUC : MIC target of >100 , Neef et al. found in 2002 from an in vitro model that 1200 mg was the optimal dose to be given if the MIC was 0.25 mg l−1 and recent studies on critically ill patients on ICUs have shown that the AUC : MIC target of >125 is reached in only 31–84% of the patients [1, 3]. In these studies AUC of ciprofloxacin was usually low, respectively 42 ± 36  and 57 ± 33.5 mg l−1 h . In a recent study in 25 critically ill patients with chronic obstructive pulmonary disease low AUC values and high variability of kinetic parameters were found with ciprofloxacin 1200 mg . However, ciprofloxacin is also widely used in patients admitted to the general hospital wards and only sparse data regarding ciprofloxacin AUC : MIC are available in this particular population. Therefore, we have measured ciprofloxacin serum concentrations in patients admitted to such wards that were given ciprofloxacin intravenously (i.v.) and evaluated the AUC : MIC ratio. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated.