METHODS: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution.
RESULTS: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin).
CONCLUSIONS: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.
METHODOLOGY: One hundred and ninety-one episodes of fever and neutropenia in 128 patients from October 1997 to December 1998 were included in a prospective, open-label, single-centre study. Patients were randomly assigned to either treatment group and evaluated as successes or failures according to defined criteria. Daily assessments were made on all patients and all adverse events recorded. Univariate and multivariate analysis of outcomes and a cost analysis were carried out.
RESULTS: There were 176 evaluable patient-episodes with 51.1% in the single-daily ceftriaxone-amikacin group and 48.9% in the ceftazidime-amikacin group. There were 50 positive blood cultures: 12 Gram-positive bacteria, 33 Gram-negative bacteria and five fungi. Pseudomonas aeruginosa (P. aeruginosa) accounted for 14% of total isolates. The overall success rate was 55.5% in the ceftriaxone group compared to 51.2% in the ceftazidime group (P = 0.56). Mean time to defervescence was 4.2 days in the single-daily group and 4.3 days in the thrice-daily group. There were nine infection-related deaths; five in the single-daily ceftriaxone group. The daily cost of the once-daily regime was 42 Malaysian Ringgit less than the thrice-daily regime. There was a low incidence of adverse effects in both groups, although ototoxicity was not evaluable.
CONCLUSIONS: The once-daily regime of ceftriaxone plus amikacin was as effective as the 'standard' combination of thrice-daily ceftazidime and amikacin with no significant adverse effects in either group. The convenience and substantial cost benefit of the once-daily regime will be particularly useful in developing countries with limited health resources and in centres with a low prevalence of P. aeruginosa.
Materials and Methods: A. hydrophila was biochemically identified and subjected to antibiotic susceptibility tests. The isolate was then intraperitoneally injected into red hybrid tilapia, and the mortality, clinicopathological changes, and LD50 were determined up to 240 h post-infection (hpi).
Results: The isolate demonstrated multiple antibiotic resistances (MAR) toward amikacin, ampicillin, cefotaxime, amoxicillin, trimethoprim-sulfamethoxazole, erythromycin, and streptomycin, with a MAR index of 0.5. The experimental infection of A. hydrophila at 105 CFU/mL in the red hybrid tilapia resulted in 100% mortality at 240 hpi. The LD50 was determined at 1.1×104 CFU/mL. Infected fish demonstrated occasional erratic swimming patterns, localized hemorrhages and depigmentation on the body and operculum areas, fin erosion, enlargement of the gall bladder, and hemorrhage in internal organs. Microscopic observation of infected fish revealed brain congestion, tubular necrosis, and glomerular shrinkage in the kidneys, necrosis of hepatocytes, and congestion of blood vessels in the liver.
Conclusion: The high virulence of A. hydrophila to the red hybrid tilapia emphasizes the importance of active, on-going monitoring of its prevalence in Malaysian tilapia farming.
Methods: 219 P. aeruginosa isolates were studied: (a) 105 clinical isolates from 1977 to 1985 (n = 52) and 2015 (n = 53), and (b) 114 environmental isolates from different fresh water sources. All isolates were subjected to ERIC-PCR typing, antimicrobial susceptibility testing and virulence factor genes screening.
Results: Clinical and environmental isolates of P. aeruginosa were genetically heterogenous, with only four clinical isolates showing 100% identical ERIC-PCR patterns to seven environmental isolates. Most of the clinical and environmental isolates were sensitive to almost all of the antipseudomonal drugs, except for ticarcillin/clavulanic acid. Increased resistant isolates was seen in 2015 compared to that of the archived isolates; four MDR strains were detected and all were retrieved in 2015. All clinical isolates retrieved from 1977 to 1985 were susceptible to ceftazidime and ciprofloxacin; but in comparison, the clinical isolates recovered in 2015 exhibited 9.4% resistance to ceftazidime and 5.7% to ciprofloxacin; a rise in resistance to imipenem (3.8% to 7.5%), piperacillin (9.6% to 11.3%) and amikacin (1.9% to 5.7%) and a slight drop in resistance rates to piperacillin/tazobactam (7.7% to 7.5%), ticarcillin/clavulanic acid (19.2% to 18.9%), meropenem (15.4% to 7.5%), doripenem (11.5% to 7.5%), gentamicin (7.7% to 7.5%) and netilmicin (7.7% to 7.5%). Environmental isolates were resistant to piperacillin/tazobactam (1.8%), ciprofloxacin (1.8%), piperacillin (4.4%) and carbapenems (doripenem 11.4%, meropenem 8.8% and imipenem 2.6%). Both clinical and environmental isolates showed high prevalence of virulence factor genes, but none were detected in 10 (9.5%) clinical and 18 (15.8%) environmental isolates. The exoT gene was not detected in any of the clinical isolates. Resistance to carbapenems (meropenem, doripenem and imipenem), β-lactamase inhibitors (ticarcillin/clavulanic acid and piperacillin/tazobactam), piperacillin, ceftazidime and ciprofloxacin was observed in some of the isolates without virulence factor genes. Five virulence-negative isolates were susceptible to all of the antimicrobials. Only one MDR strain harbored none of the virulence factor genes.
Conclusion: Over a period of 30 years, a rise in antipseudomonal drug resistance particularly to ceftazidime and ciprofloxacin was observed in two hospitals in Malaysia. The occurrence of resistant environmental isolates from densely populated areas is relevant and gives rise to collective anxiety to the community at large.
METHODS: CLSI broth microdilution methodology was used to determine antimicrobial activity and EUCAST breakpoints version 9.0 were used to determine rates of susceptibility and resistance. Isolates were also screened for the genes encoding extended-spectrum β-lactamases (ESBLs) or carbapenemases (including metallo-β-lactamases [MBLs]).
RESULTS: Between 2015 and 2017, this study collected a total of 7051 Enterobacterales isolates and 2032 Pseudomonas aeruginosa isolates from hospitalized patients in Australia, Japan, South Korea, Malaysia, the Philippines, Taiwan, and Thailand. In the Asia-Pacific region, Enterobacterales isolates that were ESBL-positive, carbapenemase-negative (17.9%) were more frequently identified than isolates that were carbapenemase-positive, MBL-negative (0.7%) or carbapenemase-positive, MBL-positive (1.7%). Multidrug-resistant (MDR) isolates of P. aeruginosa were more commonly identified (23.4%) than isolates that were ESBL-positive, carbapenemase-negative (0.4%), or carbapenemase-positive, MBL-negative (0.3%), or carbapenemase-positive, MBL-positive (3.7%). More than 90% of all Enterobacterales isolates, including the ESBL-positive, carbapenemase-negative subset and the carbapenemase-positive, MBL-negative subset, were susceptible to amikacin and ceftazidime-avibactam. Among the carbapenemase-positive, MBL-positive subset of Enterobacterales, susceptibility to the majority of agents was reduced, with the exception of colistin (93.4%). Tigecycline was active against all resistant subsets of the Enterobacterales (MIC90, 1-4 mg/L) and among Escherichia coli isolates, > 90% from each resistant subset were susceptible to tigecycline. More than 99% of all P. aeruginosa isolates, including MDR isolates and the carbapenemase-positive, MBL-positive subset, were susceptible to colistin.
CONCLUSIONS: In this study, amikacin, ceftazidime-avibactam, colistin and tigecycline appear to be potential treatment options for infections caused by Gram-negative pathogens in the Asia-Pacific region.
Methods: A cross sectional prospective study was conducted at Shaheed Ziaur Rahman Medical College Hospital, Bogura, Bangladesh among clinically suspected urinary tract infection patients from January to December, 2018. Clean-catch midstream or catheter-catch urine samples were subjected to bacteriological culture using chromogenic agar media. Antimicrobial susceptibility testing of the isolates was done by Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. Descriptive statistical methods were used for data analysis.
Results: Culture yielded a total of 537 (42.8%) significant bacterial growths including 420 (78.2%) multi drug resistant uropathogens from 1255 urine samples. Escherichia coli was the most common isolate (61.6%) followed by Klebsiella spp. (22.5%), Pseudomonas spp. (7.8%), Staphylococcus aureus (5.4%) and Enterobacter spp. (2.6%) with multi drug resistance frequency of 77.6%, 71.9%, 90.5%, 86.2% and 92.9% respectively. There was female preponderance (M:F; 1:1.97; P=0.007) but insignificant differences between paediatric and adult population (43.65% vs. 42.57%) and also among different age groups. Diabetes, chronic renal failure, fever and supra-pubic pain had significant association as co-morbidities and presentations of urinary tract infections (P<0.05). Multi drug resistance ranged from 3.7 to 88.1% including moderate to high resistance found against commonly used antibiotics like ciprofloxacin, cephalosporin, azithromycin, aztreonam, cotrimoxazole and nalidixic acid (28.6 to 92.9%). Isolates showed 2.4 to 32.2% resistance to nitrofurantoin, amikacin, netilmicin and carbapenems except Pseudomonas spp. (66.7% resistance to nitrofurantoin) and Enterobacter spp. (28.6 to 42.9% resistance to carbapenems).
Conclusion: There is very high prevalence of multi drug resistant uropathogens among hospitalized patients and emergence of carbapenem resistance is an alarming situation. Antibiotic stewardship program is highly recommended for hospitals to combat antimicrobial resistance.
Objectives: This study aimed to evaluate the patterns of intraperitoneal (IP) antibiotic utilization for the treatment of peritonitis in CAPD patients.
Materials and Methods: This is a retrospective study conducted at a tertiary hospital setting in Malaysia. Medical records of CAPD patients who were diagnosed with peritonitis and registered with National Kidney Registry from 2013 to 2018 were reviewed. Types of antibiotics used and its dose and duration were recorded and reported using the anatomical therapeutic chemical/defined daily dose (ATC/DDD) system.
Results: A total of 105 peritonitis episodes were recorded from 72 patients. The most common first-line empirical antibiotic combinations used were ceftazidime/cefazolin (40%, n = 42), followed by cefepime/cefazolin (30.5%, n = 32) and ceftazidime/cloxacillin (25.7%, n = 27). The definitive therapy for culture-proven CAPD-related peritonitis (CAPD-P) showed that vancomycin was the most frequently prescribed antibiotic (31.7%, n = 26/82), followed by amikacin (14.6%, n = 12/82), meropenem (11%, n = 9/82) and ampicillin (11%, n = 9/82). Ciprofloxacin was among the least prescribed definitive antibiotics for CAPD-P (2.4%, n = 2/82) but the DDD/100 patient-days estimates showed that it had the highest therapeutic intensity.
Conclusion: There are various IP antibiotics used for CAPD-P and the most common empirical therapy was the combination of ceftazidime and cefazolin while vancomycin is predominantly used for definitive therapy. Future studies to evaluate the clinical outcomes of the antibiotic use should be conducted to have a better insight on the efficacy of the peritonitis treatment.