BACKGROUNDAerosolized amikacin (AA) is a current option for the management of ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB.

METHODSIn this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit (ICU) in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups (AA group, n = 27 and placebo group, n = 25). Amikacin (400 mg, q8h) or saline placebo (4 ml, q8h) was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were followed up for 28 days. Bacteriological eradication, clinical pulmonary infection score (CPIS), and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28.

RESULTSThe baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group (41% vs. 14%, P= 0.024). As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication (41% vs. 16%, P= 0.049). The adjunction of AA reduced CPIS (4.2 ± 1.6 vs. 5.8 ± 2.1, P= 0.007). New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors (48% vs. 35%, P= 0.444), weaning rate (48% vs. 32%, P= 0.236), and mortality (22% vs. 32%, P= 0.427) were detected between the two groups on day 28.

CONCLUSIONSAs an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.

Administration, Inhalation ; Aged ; Amikacin ; administration & dosage ; therapeutic use ; Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Colistin ; administration & dosage ; therapeutic use ; Double-Blind Method ; Drug Resistance, Multiple, Bacterial ; Female ; Gram-Negative Bacteria ; drug effects ; pathogenicity ; Humans ; Intensive Care Units ; statistics & numerical data ; Male ; Middle Aged ; Pneumonia, Ventilator-Associated ; drug therapy

BACKGROUND/AIMS: The number of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is increasing. In an outpatient setting, there are limited therapeutic options to treat ESBL-producing pathogens. We evaluated the outcomes of amikacin outpatient parenteral antibiotic therapy (OPAT) for UTIs caused by ESBL-EC in patients not pre-treated with carbapenem. METHODS: We retrospectively evaluated the outcomes of amikacin OPAT for UTIs caused by ESBL-EC. RESULTS: From November 2011 to October 2012, eight females, who could not be hospitalized for carbapenem treatment, were treated with amikacin OPAT for nine episodes of non-bacteremic ESBL-EC UTIs. Seven of the eight patients had one or more comorbidities. Of the nine UTI cases, three had symptomatic lower UTIs and six had non-bacteremic upper UTIs. In all of the cases, symptomatic and laboratory improvements were observed following amikacin OPAT. One patient showed a delayed relapse with bilateral microabscesses 3 weeks after treatment cessation; however, a clinical and microbiological cure was eventually reached. All of the patients were able to tolerate amikacin OPAT without any significant nephrotoxicity or ototoxicity. CONCLUSIONS: Amikacin OPAT represents a feasible therapeutic option for non-bacteremic UTIs caused by ESBL-EC in settings with limited resources.
Adult ; Aged ; Aged, 80 and over ; Ambulatory Care ; Amikacin/administration & dosage/adverse effects/*therapeutic use ; Drug Administration Schedule ; Escherichia coli/*drug effects/enzymology/isolation & purification ; Escherichia coli Infections/diagnosis/*drug therapy/microbiology/urine ; Humans ; Microbial Sensitivity Tests ; Middle Aged ; Recurrence ; Remission Induction ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Urinalysis ; Urinary Tract Infections/diagnosis/*drug therapy/microbiology/urine ; Urine/microbiology ; beta-Lactamase Inhibitors/administration & dosage/adverse effects/*therapeutic use ; beta-Lactamases/*metabolism

BACKGROUND: Acinetobacter baumannii has emerged as a major cause of nosocomial outbreaks. It is particularly associated with nosocomial pneumonia and bloodstream infections in immunocompromised and debilitated patients with serious underlying pathologies. Over the last two decades, a remarkable rise in the rates of multidrug resistance to most antimicrobial agents that are active against A. baumannii has been noted worldwide. We evaluated the rates of antimicrobial resistance and changes in resistance over a 5-year period (2010–2014) in A. baumannii strains isolated from hospitalized patients in a tertiary Greek hospital. MATERIALS AND METHODS: Identification of A. baumannii was performed by standard biochemical methods and the Vitek 2 automated system, which was also used for susceptibility testing against 18 antibiotics: ampicillin/sulbactam, ticarcillin, ticarcillin/clavulanic acid, piperacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, gentamicin, amikacin, tobramycin, ciprofloxacin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute criteria, except for tigecycline, for which the Food and Drug Administration breakpoints were applied. Multidrug resistance was defined as resistance to ≥3 classes of antimicrobial agents. RESULTS: Overall 914 clinical isolates of A. baumannii were recovered from the intensive care unit (ICU) (n = 493), and medical (n = 252) and surgical (n = 169) wards. Only 4.9% of these isolates were fully susceptible to the antimicrobials tested, while 92.89% of them were multidrug resistant (MDR), i.e., resistant to ≥3 classes of antibiotics. ICU isolates were the most resistant followed by isolates from surgical and medical wards. The most effective antimicrobial agents were, in descending order: colistin, amikacin, trimethoprim/sulfamethoxazole, tigecycline, and tobramycin. Nevertheless, with the exception of colistin, no antibiotic was associated with a susceptibility rate >40% for the entire study period. The most common phenotype showed resistance against ampicillin/sulbactam, cephalosporins, carbapenems, aminoglycosides, ciprofloxacin, and tigecycline. An extremely concerning increase in colistin-resistant isolates (7.9%) was noted in 2014, the most recent study year. CONCLUSION: The vast majority of A. baumannii clinical isolates in our hospital are MDR. The remaining therapeutic options for critically ill patients who suffer from MDR A. baumannii infections are severely limited, with A. baumannii beginning to develop resistance even against colistin. Scrupulous application of infection control practices should be implemented in every hospital unit. Lastly, given the lack of available therapeutic options for MDR A. baumannii infections, well-controlled clinical trials of combinations of existing antibiotics are clearly needed.
Acinetobacter baumannii* ; Acinetobacter* ; Amikacin ; Aminoglycosides ; Anti-Bacterial Agents ; Anti-Infective Agents ; Carbapenems ; Cefotaxime ; Ceftazidime ; Cephalosporins ; Ciprofloxacin ; Colistin ; Critical Illness ; Disease Outbreaks ; Drug Resistance, Multiple ; Gentamicins ; Hospital Units ; Humans ; Imipenem ; Infection Control ; Intensive Care Units ; Pathology ; Phenotype ; Piperacillin ; Pneumonia ; Tetracycline ; Ticarcillin ; Tobramycin ; United States Food and Drug Administration

To report on Achromobacter xylosoxidans keratitis in two healthy patients who had worn contact lenses foran extended period of time. A 36-year-old female and a 21-year-old female visited our hospital with ocular pain and blurred vision. Both patients had a history of wearing soft contact lenses for over fve years with occasional overnight wear. At the initial presentation, a slit lamp examination revealed corneal stromal infiltrations and epithelial defects with peripheral neovascularization in both patients. Microbiological examinations were performed from samples of corneal scrapings, contact lenses, contact lens cases, and solution. The culture resulting from the samples taken from the contact lenses, contact lens cases, and solution were all positive for Achromobacter xylosoxidans. Confrming that the direct cause of the keratitis was the contact lenses, the frst patient was prescribed ceftazidime and amikacin drops sensitive to Achromobacter xylosoxidans. The second patient was treated with 0.3% gatifoxacin and fortifed tobramycin drops. After treatment, the corneal epithelial defects were completely healed, and subepithelial corneal opacity was observed. Two cases of Achromobacter xylosoxidans keratitis were reported in healthy young females who wore soft contact lenses. Achromobacter xylosoxidans should be considered a rare but potentially harmful pathogen for lens-induced keratitis in healthy hosts.
Achromobacter denitrificans/*isolation & purification ; Adult ; Amikacin/administration & dosage ; Anti-Bacterial Agents/*administration & dosage ; Ceftazidime/administration & dosage ; Contact Lenses, Extended-Wear/*adverse effects ; Female ; Fluoroquinolones/administration & dosage ; Gram-Negative Bacterial Infections/diagnosis/*drug therapy/*microbiology ; Humans ; Keratitis/diagnosis/*drug therapy/*microbiology ; Tobramycin/administration & dosage

OBJECTIVETo establish the rat model of chronic bacterial prostatitis and investigate the penetrability of amikacin to chronic inflammatory prostatic tissues.

METHODSA total of 180 male rats were randomly divided into a normal control group (NC, n=48), a chronic bacterial prostatitis group (CBP, n = 84) and a CBP treatment group (CBPT, n = 48). The prostates of the animals were injected with Xiaozhiling and E. coli respectively to make CBP and CBPT models. The animals of the CBPT group were treated with amikacin by intramuscular injection, their prostate tissues and sera isolated at 1-150 min after the treatment and detected for antibiotic activities, bacteria counts and pathological changes.

RESULTSObvious chronic inflammatory pathological changes including leukocyte invasion and fibre hyperplasia were observed and E. coli isolated from the prostate tissues of the rats in the CBP and CBPT groups, but no pathological changes, antibiotic activity and bacteria were detected in the the NC group. The numbers of E. coli in the prostate tissues markedly decreased with the time in the two model groups, 30 CFU/mg in the CBP rats at 28 days and 0 CFU/mg in the CBPT group at 10 days after the treatment. Obvious antibiotic activities were found in both the prostate tissues and sera at 2-150 min after the injection. No antimicrobial activities were detected at 12 hours after the treatment either in the sera or in the prostate samples. With the increase of the treatment time and decrease of the bacteria counts, the chronic inflammatory pathological changes were obviously alleviated in the CBPT group.

CONCLUSIONRat models of CBP with chronic inflammatory pathological changes can be successfully established by direct injection of Xiaozhiling and E. coli into the prostate. Amikacin, given by intramuscular injection, can penetrate into the prostate of the CBP rat and produce an antibiotic activity equal to or higher than that of the sera, which may kill sensitive bacteria in the prostate and help to reduce the inflammatory pathological changes and repair the damage to the prostate tissues.

Amikacin ; blood ; pharmacokinetics ; therapeutic use ; Animals ; Anti-Bacterial Agents ; administration & dosage ; pharmacokinetics ; therapeutic use ; Disease Models, Animal ; Escherichia coli ; drug effects ; Injections, Intramuscular ; Male ; Prostate ; drug effects ; metabolism ; microbiology ; Prostatitis ; drug therapy ; metabolism ; microbiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the changes of pharmacokinetic parameters of amikacin in the subeschar tissue fluid (STF) in the early stage of severe burns.

METHODSAmikacin concentration in the STF of 10 severely burned patients were determined by fluorescence polarization immunoassay (FPIA) at different time points after intravenous amikacin infusion of the initial dose of 400 mg given within 60 min. The pharmacokinetic parameters of amikacin were measured using 3P97 program and statistically analyzed with SPSS10.0 software.

RESULTS AND CONCLUSIONAfter the initial dose of 400 mg of amikacin, the STF concentration-time curves of amikacin were fitted in two compartment model. The pharmacokinetic parameters of amikacin in the STF were: t(1/2alpha)=(4.35-/+1.66) h, t(1/2beta)= (80.04-/+9.52) h, Vc= (13.17-/+1.32) L, AUC= (1802.49-/+285.68) microg. h.ml(-1), and CLs= (0.2272-/+0.0383) L. h(-1), demonstrating significantly lower clearance and longer elimination half life of amikacin in the STF following amikacin administration in early stage of severe burns. Elimination half-life of amikacin in the STF in severely burned patients was 28.20-44.78 times longer than that in the serum of normal volunteers, and the effective inhibitory concentration of amikacin could maintain for at least 24 h, suggesting antibiotic retention in the third space after early and short-term use of potent antibiotics and formation of antibiotic barrier in the STF, which may help prevent bacterial infection of the wound.

Adult ; Amikacin ; administration & dosage ; pharmacokinetics ; therapeutic use ; Anti-Bacterial Agents ; administration & dosage ; pharmacokinetics ; therapeutic use ; Burns ; drug therapy ; metabolism ; Extracellular Space ; metabolism ; Exudates and Transudates ; metabolism ; Female ; Humans ; Infusions, Intravenous ; Male ; Skin ; drug effects ; metabolism ; pathology

OBJECTIVETo determine the adequate timing of antibiotics application in severely burned patients by observing the dynamic changes of amikacin in blister fluid during early postburn stage.

METHODSTwenty patients in early stage of sever burns were divided into 4 groups (n=5) according to the timing of amikacin administration, namely at 3-4 h (group A), 10 h (group B, 20 h (group C), and 30 h (group D) postburn. Amikacin was administered intravenously via a single dose of 400 mg within 30 min, and at the time points of 0.25 to 7 h after completion of the infusion, the blister fluid was collected from each patient for determination of amikacin concentration with fluorescence polarization immunoassay.

RESULTSFifteen minutes after intravenous administration, amikacin could be detected in the blister fluid, reaching the highest level at 1-2 h after administration followed by gradual declination. In group B, blister fluid amikacin concentration reached 4.96+1.60 microg/ml 15 min after administration, and at the subsequent time points until 4 h, amikacin concentration was significantly higher in groups A and B than in groups C and D (P<0.05). Amikacin concentration in the blister fluid in group D was not sufficient for effective antibacterial therapy.

CONCLUSIONAmikacin administration in the early postburn stage may ensure higher amikacin concentration in the blister fluid and wound exudate. Better antibacterial effect can be expected when amikacin is applied within the initial 10 h postburn.

Adult ; Amikacin ; administration & dosage ; analysis ; Anti-Bacterial Agents ; administration & dosage ; analysis ; Blister ; drug therapy ; pathology ; Burns ; drug therapy ; pathology ; Exudates and Transudates ; chemistry ; Female ; Humans ; Infusions, Intravenous ; Male ; Young Adult

OBJECTIVETo analyze the use of antibiotics and the drug resistance of Pseudomonas aeruginosa in the burn ward of our hospital in the past 11 years, so as to optimize the use of antibiotics in the future.

METHODSBacterial epidemiology during 1991-2001 in our burn ward was investigated. The change of the drug resistance of Pseudomonas aeruginosa was observed by defined daily dose (DDD) of antibiotics in adult patients and by the ranking of antibiotic administration days.

RESULTS(1) Staphylococcus aureus (10.53%-34.40%) and Pseudomonas aeruginosa (75.66%-11.47%) were dominant in our burn ward. (2) Predominant antibiotics used included Penicillin, Amikacin, Vancomycin, Imipenem and Ceftazidime. (3) There was increasing drug resistance of Pseudomonas aeruginosa to the following antibiotics ranking in following order: Piperacillin (41.57%-100.00%), Imipenem (36.36%-98.46%), Ceftazidime (23.46%-97.85%), Amikacin (13.16%-100.00%) and ciprofloxacin (6.90%-100.00%).

CONCLUSIONThere was increasing drug resistance of Pseudomonas aeruginosa to all antibiotics, which might be related to antibiotic abuse.

Amikacin ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Burn Units ; Ceftazidime ; therapeutic use ; Drug Administration Schedule ; Drug Resistance, Bacterial ; drug effects ; Humans ; Imipenem ; therapeutic use ; Penicillins ; therapeutic use ; Pseudomonas aeruginosa ; drug effects ; Vancomycin ; therapeutic use

The histopathological alterations in the vestibule due to aminoglycosides are well defined. Although there are reports comparing the vestibulotoxic effects of the many aminoglycosides, this is the first study to compare the effects of the most commonly used aminoglycosides i.e., streptomycin, gentamicin, amikacin and netilmicin administered both transtympanically and systemically. The transtympanic and systemic administration of each aminoglycoside caused similar histopathological alterations in the vestibule. The most severe degeneration in the cristae ampullaris, utriculus and sacculus was observed after streptomycine administration. The severity of the vestibular damage in terms of magnitude was in the order of streptomycine, gentamicin, amikacin, and netilmicin.
Amikacin/administration & dosage/*poisoning ; Animals ; Comparative Study ; Gentamicins/administration & dosage/*poisoning ; Guinea Pigs ; Injections, Intraperitoneal ; Netilmicin/administration & dosage/*poisoning ; Streptomycin/administration & dosage/*poisoning ; Tympanic Membrane ; Vestibule/*drug effects

AIMTo assess the efficacy and safety of anal submucosal injection (ASI) of amikacin in chronic bacterial prostatitis (CBP).

METHODSFifty male outpatients with CBP were randomly divided into two groups. Thirty cases of ASI group were given amikacin 400 mg daily by ASI for ten times and the other twenty cases of intramuscular injection (IM) group were given the same drug daily by IM. All patients were evaluated with NIH-Chronic prostatitis symptom index (NIH-CPSI), the bacteria culture of the expressed prostate secretion (EPS), proctoscopic examination, rectal biopsy and the clinical manifestation were checked at pretreatment and on day 7 and 90 after cessation of therapy.

RESULTSThe cure rate, apparent effective rate and effective rate of ASI group and IM group were 33.3% vs 5% (P<0.05), 43.3% vs 10% (P<0.05) and 16.7% vs 20% (P>0.05), respectively. The score of NIH-CPSI in both of ASI group and IM group decreased significantly 7 days after cessation of therapy, both ASI and IM of amikacin could relieve symptoms within a short time. However, 3 months after cessation of therapy the score of NIH-CPSI in ASI group continued down in spite of no significant differences compared with 7 days after cessation of therapy, but the score of IM group was rebound nearly closed to level of pretreatment at 23.8 8.5 and significantly higher than that of ASI group. The amount of white blood cell (WBC) of EPS in ASI group increased slightly at 7 days after cessation of therapy without significant difference with pretreatment (P>0.05), but it significantly decreased at 3 months after cessation of therapy, the amount of WBC of EPS in ASI group was lower than that of IM group at 3 months after cessation of therapy (P<0.05). Proctoscopic examination of anal canal were normal after ASI therapy and the rectum biopsy showed no obvious histopathologic abnormality at the site of injection except mild focal submucosal infiltration of lymphocytes and plasma cells at 7 days after cessation of therapy which disappeared on 3 months after cessation of therapy. All patients had no evident complications.

CONCLUSIONASI could be recommended as a new safe, effective, painless method of antibiotics administration in the treatment of CBP.

Adult ; Amikacin ; administration & dosage ; adverse effects ; Anal Canal ; cytology ; Anti-Bacterial Agents ; administration & dosage ; adverse effects ; Biopsy ; Gram-Negative Bacterial Infections ; drug therapy ; Humans ; Injections ; methods ; Male ; Middle Aged ; Mucous Membrane ; Prostatitis ; drug therapy ; microbiology ; Treatment Outcome