Increased resistance to amikacin in a neonatal unit following intensive amikacin usage

Abstract

Gram-negative isolates from blood and cerebrospinal fluid were monitored for 1 year before and for 1 year after the first-line aminoglycoside in a busy pediatric department was changed from gentamicin to amikacin.In the general pediatric wards, the switch to amikacin resulted in no change in resistance of nosocomial gram-negative infections to either amikacin (0%Yo before and after) or gentamicin (23.9% [before] versus 26.5% [after]). In the neonatal unit, the switch to amikacin was followed by an outbreak of Serratia spp. that were commonly resistant to amikacin but susceptible to gentamicin. This outbreak abated spontaneously. In the year after the change in aminoglycoside usage, the resistance to amikacin of nosocomially acquired gram-negative infections increased from 7.6 to 27.7% (P < 0.001), and the resistance to gentamicin decreased from 71.2 to 60.2% (P = 0.07). The increase in amikacin resistance of gram-negative bacilli other than Serratia spp. has persisted for more than a year after the introduction of amikacin as the sole aminoglycoside. The different effects observed in the two sections of the pediatric department may be related to the more intensive usage of aminoglycosides in the neonatal unit.The effect of predominant amikacin usage on susceptibility of gram-negative bacteria (GNB) to aminoglycosides is well documented (1, 5-7, 11, 13, 17, 19, 22-24, 28, 30). Those studies showed that frequent usage of amikacin usually results in no increase or only a slight increase in resistance to amikacin and a decrease in resistance to other aminoglycosides. However, in none of those studies were communityand hospital-acquired infections analyzed separately. Also, GNB isolated from all sites were included, and except in one study (6), invasive disease was not separated from colonization without invasion. Because all infections were combined, increases in amikacin resistance of nosocomial infections may have been "diluted" by the inclusion of large numbers of community-acquired isolates. Similarly, combining isolates from all sections of a hospital may mask significant changes in a specific area.Further motivation for this study was the lack of information on antimicrobial resistance levels in relation to aminoglycoside usage in developing countries, where overcrowded hospitals with very high rates of patient turnover are common.Because of increasing resistance of GNB to gentamicin, both the neonatal and general pediatric wards of our hospital changed to amikacin as the sole aminoglycoside for suspected GNB infections.The purpose of this study was to record prospectively the effect of intensive amikacin usage on the aminoglycoside resistance patterns of invasive hospital-acquired GNB in a busy pediatric department. MATERIALS AND METHODSPatient population. Baragwanath is the major hospital serving Soweto, South Africa (population of 1 to 2 million).

Antimicrobial susceptibility pattern of clinical isolates of Pseudomonas aeruginosa isolated from patients of lower respiratory tract infections

“…In the present study the rate of amikacin resistance was found to be relatively high i.e. 35% however it may in accordance with Friedland et al who reported that amikacin resistance related to more intensive usage of amino glycosides (Friedland et al 1992). The increasing rate of amikacin in Pakistan was also reported by Akhtar N i.e.…”

Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success

“…Our model suggests the risk that this benefit would come at the cost of promoting high-level fluoroquinolone resistance; however, the properties of these agents to date seem to minimize such risk. Although resistance to newer fluoroquinolones has been reported (27), high-level resistance remains largely associated with previous treatment, and there has been only limited evidence of clonal spread of fluoroquinolone-resistant pneumococci (10)(11)(12)(13)28). These observations may imply a considerable fitness cost from acquiring incremental mutations associated with high-level fluoroquinolone resistance, a finding recently confirmed in animal models (28).…”

“…This result occurs when the delay leads to a large increase in Y 1 and when the new drug selects for Y 2 easily from this enlarged pool of Y 1 . Among the atypical scenarios (N ϭ 233), parameters involved in the acquired mechanism for resistance [i.e., e 12 , P, and Y 1 (0)] have means significantly higher than among the typical scenarios. Specifically, e 12 represents the likelihood of this selection and is shown to best differentiate an atypical scenario from a typical one (C-statistic ϭ 0.924).…”

“…These bacteria are resistant to the old drug but susceptible to the new drug. Use of the new drug accelerates clearance of both the susceptible (Y 0 ) and the low-level resistant (Y 1 ) strains by a rate p 2 (t), but it also selects for the highly resistant (Y 2 ) strain to emerge from a proportion (e 12 ) of the treated Y 1 hosts. We assume that the treatment is empiric, without drug sensitivity testing, as in many community-acquired infections; thus, the rate at which an individual receives an antibiotic is assumed to be independent of the drug sensitivity of the strain the individual carries.…”

“…For a bacterial pathogen that is increasingly resistant to a widely prescribed agent, promoting the use of a novel drug with activity against the resistant strains leads to fewer treatment failures and delivers benefits to current patients (4,9). On the other hand, switching to a new drug imposes a selective pressure in favor of strains that are resistant to even the new antibiotic (10)(11)(12). Thus, we may expect that such a switch achieves the first objective at the expense of the second.…”