Search

Purpose: Recurrent urinary tract infections are common in complex pediatric urological cases, particularly those requiring clean intermittent catheterization. At our institution gentamicin bladder irrigations have been used for antimicrobial prophylaxis and to treat symptomatic bacteriuria, particularly when the infection does not involve the upper urinary tract. The purpose of this study was to assess the safety of this therapy., Materials and Methods: A retrospective study was performed of all children treated with gentamicin bladder irrigations from 1999 to 2004. The dose was 14 mg gentamicin in 30 ml saline instilled via catheter once or twice daily. Serum creatinine and random gentamicin levels were obtained according to a protocol based on risk of gentamicin toxicity. Patient demographics, laboratory results and outcomes were abstracted from the medical records., Results: A total of 80 patients (38 males and 42 females) were identified. Median patient age was 10 years and median duration of treatment was 90 days. No patient had detectable serum gentamicin levels greater than 0.4 mg/dl. Small increases in serum creatinine were seen in 3 patients, all of whom had chronic renal insufficiency. A total of 21 patients (26%) had breakthrough UTIs, of which 5 (24%) were gentamicin resistant. No adverse events were documented., Conclusions: Gentamicin bladder irrigations are a helpful adjunct in the management of complex pediatric urological cases involving recurrent symptomatic bacteriuria. We no longer require intensive laboratory monitoring of low risk patients at our institution.

The Innofluor fluorescence polarization immunoassay (FPIA) kits for gentamicin, tobramycin, amikacin and vancomycin were evaluated on an Abbott TDX analyser. Intra-assay reproducibility was excellent with a coefficient of variation of <3% for all analytes. The coefficient of variation for inter-assay reproducibility was usually <5%. Assay linearity was good and standard curve stability was seen with kits of the same batch for at least 32 days. Using clinical samples, the results obtained with the Innofluor FPIA reagents correlated well with those obtained using Abbott FPIA reagents, but Innofluor gentamicin and amikacin results were slightly higher than Abbott results (P < 0.001). Results of UK NEQAS returns showed acceptable accuracy for the Innofluor kits, but mean Innofluor gentamicin returns were 4% higher (P = 0.001) and mean vancomycin returns were 5% lower (P = 0.001) than overall mean returns. Innofluor and Abbott vancomycin assay reagents showed similar cross-reactivity to degraded vancomycin.

A time-kill curve employing nine sampling times over 6 h was used to provide data which were then used to develop a theoretical (best-fit) curve. From the theoretical curve parameters describing the rate of kill (alpha), time from addition of antibiotic to initiation of killing (d) and a function of the degree of killing observed (Ym/Yo) were defined. The area-under-the-curve (AUC) was calculated from the theoretical curve. The variability of each parameter was assessed using a theoretical curve to fit the data from experiments done on three occasions and in triplicate. In terms of the parameters alpha, d, Ym/Yo and AUC, no synergy was demonstrated with combinations of piperacillin/tazobactam plus ciprofloxacin or gentamicin when compared with single antibiotics. The AUC represents the best summary parameter of a time-kill curve but should be supported by other parameters describing the best-fit curve.

The agar dilution chequerboard technique of studying antimicrobial interactions was assessed by testing a representative beta-lactam (piperacillin/tazobactam), aminoglycoside (gentamicin) and fluoroquinolone (ciprofloxacin) against themselves, that is piperacillin/tazobactam plus piperacillin/tazobactam, gentamicin plus gentamicin and ciprofloxacin plus ciprofloxacin. In addition, combinations of piperacillin/tazobactam plus gentamicin or ciprofloxacin were also tested against Enterobacteriaceae and Acinetobacter spp. in triplicate. The agar dilution chequerboard technique did not reliably show addition when agents were combined with themselves, and there was also considerable variation when beta-lactam plus aminoglycoside or fluoroquinolone combinations when tested in triplicate. These observations, and problems with the design of the method, indicate that the chequerboard technique should be used only with adequate controls and replication, and then interpreted with extreme caution; ideally, it should not be used as a method of assessing antimicrobial interactions.

Three new immunoassays for determination of serum gentamicin concentration were assessed: a latex agglutination assay (Technicon), an enzyme immunoassay (EMIT 2000) and a multi-layer thin-film immunoassay (Opus). All three were easy to use, had good within- and between-assay reproducibility, good reliability and acceptable linearity. The standard curve stability was shortest with the latex agglutination assay and longest with the thin-film. The thin-film assay calibrators gave approximately double the expected concentration when assayed by polarisation fluoroimmunoassay but this did not effect the assay's performance. When compared with the polarisation fluoroimmunoassay results of patient samples, all three methods gave an excellent correlation. The technical aspects of these three methods make them acceptable for clinical use.

To determine whether daily intraventricular injection of gentamicin sulfate is ototoxic, adult male rabbits were given 0.2 ml of saline (group 1; n = 8) or 0.25 mg/kg of gentamicin sulfate in 0.2 ml of saline (group 2; n = 7) by intraventricular infusion once a day for 21 d. All rabbits were also given intramuscular gentamicin sulfate, 2 mg/kg, twice daily. Before and after antibiotic treatment, brainstem auditory evoked responses (BAERs) were recorded. During the experimental period, neurologic examinations were performed on all rabbits. After treatment, the animals were euthanized; brain tissue and cochleas were then removed for histopathologic examination. The ratios of neurologic abnormalities observed in group 1 and 2 animals, respectively, were 0/8 and 5/7; of abnormal BAERs, 0/8 and 5/7; of abnormal brain morphology, 2/5 and 6/6; and of abnormal cochlear morphology, 0/6 and 7/7. The electrophysiologic evidence of auditory deficit and the structural evidence of ototoxic insult are significantly associated (p less than or equal to 0.006) with intraventricularly administered gentamicin sulfate. These data suggest that intraventricular gentamicin should be used with caution.

The adenylytransferase/acetyltransferase methods of gentamicin assay have been evaluated for accuracy, speed, and cost. For a comparable cost of materials the latter method is more accurate than that using the adenylytransferase enzyme. The acetyltransferase method is much quicker than the adenyltransferase due to the shorter time necessary for radioactive counting. Sonication is an easier method of enzyme preparation than the previously used osmotic shock technique. The acetyltransferase method is reproducible and there was a very good correlation between it and a microbiological agar-plate diffusion method.

To determine whether daily intraventricular injection of gentamicin sulfate would cause neurologic or morphologic abnormalities of the central nervous system, adult male rabbits were given gentamicin sulfate, 2 mg/kg, intramuscularly twice a day plus saline, 0.2 ml (group 1), or gentamicin, 0.05 mg/kg (group 2), 0.25 mg/kg (group 3), or 0.5 mg/kg (group 4), given as the sulfate intraventricularly once a day. The majority of the animals in group 4 developed neurologic abnormalities which progressed to death in animals that were not euthanized; neuropathologic studies revealed chemical ventriculitis and meningitis that were associated with high levels of gentamicin in the cerebrospinal fluid and tissue of the central nervous system. Similar neurologic and morphologic changes were seen in most animals of group 3 but not in rabbits of groups 1 and 2. The ototoxicity and nephrotoxicity of gentamicin are well known; these data indicate that it may be toxic to the central nervous system as well.

Five geographically separate outbreaks of hospital acquired infection caused by gentamicin-resistant strains of Serratia marcescens occurred in the period October 1977 to January 1980 in southwest England. The patients affected were in wards for general or urological surgery, or in neurosurgical, cardiothoracic or general intensive therapy units. Asymptomatic colonization was more common than symptomatic infection, although deaths and serious infections occurred. Control of spread of the bacteria proved difficult. Most strains were resistant to many currently available antibiotics besides gentamicin; only one strain became resistant to amikacin. Representative isolates where characterized by O serotype, bacteriophage type, antibiotic sensitivity pattern, production of beta-lactamases and amino-glycoside-aminocyclitol (ACAG)-modifying enzymes, and plasmid visualization. Plasmid studies provided information that complemented conventional typing methods in determining epidemiological relationships among the outbreaks.

A substrate-labelled fluoroimmunoassay (SLFIA) for gentamicin was used to assay netilmicin by substituting serum calibrators containing netilmicin. The assay proved highly reproducible and the results obtained showed a good correlation with the results of EMIT and microbiological assays.

A Staphylococcus aureus strain, resistant to aminoglycosides, including gentamicin and tobramycin, and to penicillin, lincomycin, and other antibiotics, caused an outbreak of hospital infection in a surgical ward which spread to the intensive-therapy unit and to two other hospitals. 21 patients were colonised and 9 of these had overt clinical infection. Administration of antibiotics to which the staphylococcus was resistant was associated with colonisation. The use of gentamicin, tobramycin, and lincomycin in these hospitals has increased as has the occurrence of bacterial resistance to these agents. An antibiotic policy to control their use is essential to preserve their value in life-threatening infections by bacteria resistant to other agents.