- The Fluorescent D-Amino Acid NADA as a Tool to Study the Conditional Activity of Transpeptidases in Escherichia coli. [Journal Article]
- FMFront Microbiol 2018; 9:2101
- The enzymes responsible for the synthesis of the peptidoglycan (PG) layer constitute a fundamental target for a large group of antibiotics. The family of β-lactam antibiotics inhibits the DD-transpep...
The enzymes responsible for the synthesis of the peptidoglycan (PG) layer constitute a fundamental target for a large group of antibiotics. The family of β-lactam antibiotics inhibits the DD-transpeptidase (TPase) activity of the penicillin binding proteins (PBPs), whereas its subgroup of carbapenems can also block the TPase activity of the LD-TPases. D-Ala fluorescent probes, such as NADA, are incorporated into the PG presumably by TPases in Escherichia coli and can be used to study conditions that are required for their function. Of all LD-TPases of E. coli, only LdtD was able to incorporate NADA during exponential growth. Overproduction of LdtD caused NADA to be especially inserted at mid cell in the presence of LpoB-activated PBP1b and the class C PBP5. Using the NADA assay, we could confirm that LpoB activates PBP1b at mid cell and that CpoB regulates the activity of PBP1b in vivo. Overproduction of LdtD was able to partly compensate for the inhibition of the cell division specific class B PBP3 by aztreonam. We showed that class A PBP1c and the class C PBP6b cooperated with LdtD for NADA incorporation when PBP1b and PBP5 were absent, respectively. Besides, we proved that LdtD is active at pH 7.0 whereas LdtE and LdtF are more active in cells growing at pH 5.0 and they seem to cooperate synergistically. The NADA assay proved to be a useful tool for the analysis of the in vivo activities of the proteins involved in PG synthesis and our results provide additional evidence that the LD-TPases are involved in PG maintenance at different conditions.
- A case of pediatric patient with acute enteritis due to CTX-M-1 5 extended-spectrum β-lactamase-producing Salmonella Blockley. [Journal Article]
- JJJpn J Antibiot 2016; 69(5):343-346
- This clinical case report concerns a pediatric patient with acute enteritis caused by multi-drug resistant Salmonella enterica serovar Blockley (Salmonella Blockley). A 3-year-old boy presented to ou...
This clinical case report concerns a pediatric patient with acute enteritis caused by multi-drug resistant Salmonella enterica serovar Blockley (Salmonella Blockley). A 3-year-old boy presented to our emergency room with a 5-day history of fever, abdominal pain, and bloody diarrhea. Stool culture tested positive for a Salmonella species, while the blood culture was negative. The patient was successfully treated with an oral antibiotic regimen of fosfomycin. The stool isolate was found to be resistant to multiple drugs, including cefpodoxime, cefotaxime, ceftazidime, and aztreonam, and was confirmed to be a CTX-M-15 extended-spectrum β-lactamase (ESBL)-producing strain of Salmonella Blockley. This is the first report of a pediatric patient in Japan with acute enteritis caused by a CTX-M-15 ESBL- producing strain of Salmonella Blockley.
- Sensitivity surveillance of Pseudomonas aeruginosa isolates for several antibacterial agents in Chubu area (2013-2014). [Journal Article]
- JJJpn J Antibiot 2016; 69(5):327-341
- We investigated the susceptibility to antibacterial agents of 186 clinical isolates of Pseudomonas aeruginosa isolated from medical facilities in Gifu, Aichi, Toyama, and Fukui prefectures from Octob...
We investigated the susceptibility to antibacterial agents of 186 clinical isolates of Pseudomonas aeruginosa isolated from medical facilities in Gifu, Aichi, Toyama, and Fukui prefectures from October 2013 to February 2014. MIC₅₀/₉₀ of piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ), cefepime (CFPM), imipenem (IPM), meropenem (MEPM), doripenem (DRPM), aztreonam (AZT), ciprofloxacin (CPFX), levofloxacin (LVFX), amikacin (AMK) and colistin (CL) against P aeruginosa was 8/32, 4/32, 2/8, 2/16, 1/32, 0.5/8, 0.25/4, 8/32, 0.25/8, 0.5/16, 4/8 and 1/1pg/mLrespectively. Two strains of multidrug resistant P aeruginosa were isolated (1.1%). They were isolated from the respiratory tract, intra-abdominal, and urinary infection. The susceptible ratio against P aeruginosa derived from intra-abdominal infection for carbapenem was lower than those from respiratory tract and urinary infection. The susceptible ratio against P aeruginosa derived from urinary infection for penicillin, cephem, monobactam, and fluoroquinolone was lower than those from respiratory and intra-abdominal infection. It is meaningful to pay attention to the susceptibility to antibacterial agents in each clinical specimen from infected organ.
- Clinical experience with colistin in 9 Japanese patients with infection due to multi-drug resistance pathogens. [Journal Article]
- JJJpn J Antibiot 2016; 69(5):319-326
- Colistin is a polypeptide antibiotic of the polymyxin family (polymyxin E) which has been reported to be active against many multidrug-resistant (MDR) Gram-negative aerobic bacteria collected across ...
Colistin is a polypeptide antibiotic of the polymyxin family (polymyxin E) which has been reported to be active against many multidrug-resistant (MDR) Gram-negative aerobic bacteria collected across the globe. While this agent was not currently licensed in Japan, the emergence of MDR organisms has necessitated its off-label used in the country. However, colistin was approved in March, 2015. This retrospective observational report includes nine patients with MDR Gram-negative infections due to Pseudomonas aeruginosa (n=6) and Klebsiella spp. (n=3) who received intravenous colistin therapy as part of their antimicrobial regimen. The median age and duration of administration were 40 years (range 7-90) and 8 days (range 1-19). Clinical success was observed in all eight patients for whom efficacy could be evaluated. Two patients encountered colistin related adverse effects 22.2% (2/9). In both cases the nephrotoxicity and dysgeusia resolved after discontinuation of colistin therapy. In vitro studies conducted with these clinical isolates of P aeruginosa displayed synergy with the combination of colistin plus ceftazidime, rifampicin, meropenem or aztreonam. This report provides early evidence that colistin is generally safe, effective and demonstrates in vitro synergy when used in combination for the management of MDR Gram-negative pathogens derived from Japanese patients.
- Synergy of nebulized phage PEV20 and ciprofloxacin combination against Pseudomonas aeruginosa. [Journal Article]
- IJInt J Pharm 2018 Sep 14
- Nebulization is currently used for delivery of antibiotics for respiratory infections. Bacteriophages (or phages) are effective predators of pathogens including Pseudomonas aeruginosa commonly found ...
Nebulization is currently used for delivery of antibiotics for respiratory infections. Bacteriophages (or phages) are effective predators of pathogens including Pseudomonas aeruginosa commonly found in the lungs of patients with cystic fibrosis (CF). It is known that phages and antibiotics can potentially show synergistic antimicrobial effect on bacterial killing. In the present study, we investigated synergistic antimicrobial effect of phage PEV20 with five different antibiotics against three P. aeruginosa strains isolated from sputum of CF patients. The antibiotics included ciprofloxacin, tobramycin, colistin, aztreonam and amikacin, which are approved by U.S Food and Drug Administration (FDA) for inhaled administration. Phage and antibiotic synergy was determined by assessing bacterial killing performing time-kill studies. Among the different phage-antibiotic combinations, PEV20 and ciprofloxacin exhibited the most synergistic effect. Two phage-ciprofloxacin combinations, containing 1/4 and 1/2 of the minimum inhibitory concentration (MIC) of ciprofloxacin against P. aeruginosa strains FADD1-PA001 (A) and JIP865, respectively were aerosolized using both air-jet and vibrating mesh nebulizers and the synergistic antibacterial activity was maintained after nebulization. Air-jet nebulizer generated droplets with smaller volume median diameters (3.6-3.7 µm) and slightly larger span (2.3-2.4) than vibrating mesh nebulizers (5.1-5.3 µm; 2.1-2.2), achieving a higher fine particle fraction (FPF) of 70%. In conclusion, nebulized phage PEV20 and ciprofloxacin combination shows promising antimicrobial and aerosol characteristics for potential treatment of respiratory tract infections caused by drug-resistant P. aeruginosa.
- Comparison of five commonly used automated susceptibility testing methods for accuracy in the China Antimicrobial Resistance Surveillance System (CARSS) hospitals. [Journal Article]
- IDInfect Drug Resist 2018; 11:1347-1358
- CONCLUSIONS: None of the five automated systems met the criteria for acceptable AST performance, but Vitek 2 provided a relatively accurate and conservative performance for most of the antimicrobials.
- The rates of quinolone, trimethoprim/sulfamethoxazole and aminoglycoside resistance among Enterobacteriaceae isolated from urinary tract infections in Azerbaijan, Iran. [Journal Article]
- GHGMS Hyg Infect Control 2018; 13:Doc07
- Aim: Antibiotic susceptibility patterns help to select appropriate empirical treatments of urinary tract infections (UTIs). This study aimed to investigate antibiotic resistance among Enterobacteria...
Aim: Antibiotic susceptibility patterns help to select appropriate empirical treatments of urinary tract infections (UTIs). This study aimed to investigate antibiotic resistance among Enterobacteriaceae isolated from UTIs in Azerbaijan, Iran. Methods: This study was carried out during 2016 in hospitals located in Tabriz, Urmia, and Khoy. Midstream urine specimens were cultured and identified by the standard methods. Susceptibility testing was carried out using the disk diffusion agar method for cefotaxime, ceftazidime, ceftriaxone, cefoxitin, imipenem, meropenem, ertapenem, cefepime, ampicillin, cefazolin, cefuroxime, aztreonam, nitrofurantoin, and fosfomycin and the agar dilution method for MIC determination of aminoglycosides, quinolones, sulfamethoxazole, and trimethoprim. Results: A total of 219 non-duplicated Enterobacteriaceae were isolated from UTIs. According to the agar dilution assay, the following resistance rates were determined: trimethoprim/sulfamethoxazole (co-trimoxazole) 69.8%, nalidixic acid 68.9%, ciprofloxacin 66.2%, levofloxacin 58.5%, tobramycin 47.9%, kanamycin 39.3%, gentamicin 27.8%, and amikacin 5.5%. High levels of resistance were observed to trimethoprim (78.5%), sulfamethoxazole (88.1%), ampicillin (86.3%), and cephazoline (79.4%). Conclusion: The most effective agents against Enterobacteriaceae were fosfomycin, carbapenems, and amikacin. Quinolones, trimethoprim and sulfamethoxazole are not appropriate for empirical therapy due to high levels of resistance. Amikacin is more effective among aminoglycosides and may be more effective, in complicated cases, when used in combination with fosfomycin and carbapenems.
- Simplified aztreonam dosing in patients with end stage renal disease: results of a Monte Carlo simulation. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Aug 27
- The manufacturer-labeled aztreonam dosing in patients with a creatinine clearance of <10 mL/min/1.73m2 is complex. It is unknown if simpler post-hemodialysis dosing administered once daily or thrice ...
The manufacturer-labeled aztreonam dosing in patients with a creatinine clearance of <10 mL/min/1.73m2 is complex. It is unknown if simpler post-hemodialysis dosing administered once daily or thrice weekly can reliably achieve pharmacodynamic goals. We found that 1 or 2 grams once daily post-hemodialysis had a >90% probability of target attainment up to an MIC of 4 or 8mg/L, respectively. Thrice weekly dosing should generally be avoided except in non-severe infections where the MIC is ≤0.5mg/L.
- Antimicrobial resistance and pathogen distribution in hospitalized burn patients: A multicenter study in Southeast China. [Multicenter Study]
- MMedicine (Baltimore) 2018; 97(34):e11977
- Burn infections pose a serious obstacle to recovery. To investigate and analyze the antimicrobial resistance and distribution of pathogenic bacteria among hospitalized burn patients. A 3-year retrosp...
Burn infections pose a serious obstacle to recovery. To investigate and analyze the antimicrobial resistance and distribution of pathogenic bacteria among hospitalized burn patients. A 3-year retrospective study was conducted in the southeast of China.The electronic medical records system was used to collect all clinical data on 1449 hospitalized patients from Fujian Medical University Union Hospital, the 180th Hospital of Chinese People's Liberation Army (PLA), the 92nd Hospital of PLA, and the First Hospital of Longyan City.A total of 1891 strains of pathogenic bacteria were detected from 3835 clinical specimens, and the total detection rate was 49.3% (1891/3835). The main pathogens were gram-negative bacteria (1089 strains; 57.6%), followed by gram-positive bacteria (689 strains; 36.4%), and fungi (113 strains; 6.0%). The predominant five bacteria were Staphylococcus aureus (19.0%), Acinetobacter baumannii (17.6%), Pseudomonas aeruginosa (16.7%), Klebsiella pneumoniae (7.4%), and Enterococcus faecalis (4.5%). Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 74.1% (265/359) of S aureus isolates. Staphylococcus epidermidis accounted for 40.6% (69/170) of coagulase-negative staphylococcal isolates, 72.5% (50/69) of which were methicillin-resistant Staphylococcus epidermidis (MRSE). Both MRSA and MRSE were 100% resistant to penicillin and ampicillin. A baumannii was the most commonly isolated strain of gram-negative bacteria with 100% resistance to ampicillin, amoxicillin, amoxicillin/clavulanic acid, and aztreonam. More than 80% of K pneumoniae isolates were resistant to ampicillin, amoxicillin and cefazolin. More than 80% of Escherichia coli isolates were resistant to ampicillin, piperacillin, cefazolin, amoxicillin, tetracycline, and sulfamethoxazole trimethoprim. The detection rates of extended-spectrum β-lactamases (ESBL) among K pneumoniae and E coli isolates were 44.6% (62/139) and 67.2% (41/61), respectively. Low-resistance antibiotics included teicoplanin, tigecycline, vancomycin, and linezolid.The pathogens presented high resistance to antimicrobial agents, especially MRSA and A baumannii. Monitoring of bacterial population dynamics should be established to inhibit the progression of bacterial resistance.
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- Initiative to reduce aztreonam use in patients with self-reported penicillin allergy: Effects on clinical outcomes and antibiotic prescribing patterns. [Journal Article]
- AJAm J Health Syst Pharm 2018 Sep 01; 75(17 Supplement 3):S58-S62
- CONCLUSIONS: After implementation of an initiative to encourage the use of cephalosporins rather than aztreonam in patients with SRPA, the rate of clinical response and cephalosporin use increased and rates of exposure to aztreonam and fluoroquinolones decreased.