scholarly journals Tasked with a Challenging Objective: Why Do Neutrophils Fail to Battle Pseudomonas aeruginosa Biofilms

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 283 ◽  
Author(s):  
Jennifer Geddes-McAlister ◽  
Abirami Kugadas ◽  
Mihaela Gadjeva

Multidrug-resistant (MDR) bacterial infections are a leading cause of mortality, affecting approximately 250,000 people in Canada and over 2 million people in the United States, annually. The lack of efficacy of antibiotic-based treatments is often caused by inability of the drug to penetrate bacterial biofilms in sufficient concentrations, posing a major therapeutic challenge. Here, we review the most recent information about the architecture of Pseudomonas aeruginosa biofilms in vivo and describe how advances in imaging and mass spectroscopy analysis bring about novel therapeutic options and challenge existing dogmas.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S580-S581
Author(s):  
Robert K Flamm ◽  
Michael A Pfaller ◽  
Paul G Ambrose ◽  
David Andes ◽  
John S Bradley ◽  
...  

Abstract Background In 2015 USCAST, the National Advisory Committee for the United States (US) to EUCAST, produced a report (Version 1.0) on their website (www.uscast.org) re-evaluating fluoroquinolone (FQ) breakpoint interpretive criteria (IC) based on analysis of current microbiology and pharmacokinetic/pharmacodynamic (PK/PD) data. EUCAST initiated a consultative process using USCAST analyses in an effort to update FQ IC, released in 2017. CLSI formed an ad-hoc working group in late 2015 to review the USCAST FQ document and formulate questions about content. In 2018, USCAST released V1.3 of the FQ document and CLSI subsequently published updated FQ MIC IC in the M100-S29 (2019) document. This study evaluated the impact on susceptibility (S) rates for US surveillance data that these IC changes created. Methods Clinical isolates (reference broth microdilution MIC) from 2016–2018 US SENTRY Program were analyzed for S based on current and previous IC. FQ results for ciprofloxacin (CIP), levofloxacin (LEV), and moxifloxacin (MOX) were evaluated. Benchmark S comparison data for meropenem, cefepime, piperacillin–tazobactam and delafloxacin (new FQ) were also included. Results S rates for Enterobacteriaceae (ENT;Figure) were reduced by 3.8/3.7% for CIP/LEV (CLSI) and 2.3/2.5% (EUCAST). MOX-S rate vs. ENT declined 5.7% (EUCAST). Although reductions in S occurred for most organism groups, K. pneumoniae (6.0/5.5% for CIP/LEV [CLSI] and 4.0/4.2% [EUCAST]) and S. marcescens (7.4/4.1% for CIP/LEV [CLSI] and 4.1/5.0% [EUCAST]) reductions were among the largest changes. For Pseudomonas aeruginosa (PSA), CIP-S decreased 6.8% and LEV-S 10.1% (CLSI); but potential for false-S results remain using CLSI IC (5 pathogens). Conclusion USCAST’s comprehensive analyses of FQ IC in 2015 led to revised breakpoints for most organism/drug combinations among ENT and PSA compared with those being used before. USCAST analysis was most influenced by PK/PD in vivo data as current clinical outcomes data by MIC was limited. Awareness and interactions (both formal and informal) among breakpoint setting organizations has modified FQ ICs which are lower than previously recommended, and although not perfectly harmonized in time and detail, this represents a successful model. Disclosures All authors: No reported disclosures.


Author(s):  
Bekana K. Tadese ◽  
Anna Nutt ◽  
Ifrah Chaudhary ◽  
Charlene Offiong ◽  
Charles Darkoh

Abstract Klebsiella pneumoniae carbapenemase-producing P. aeruginosa (KPC-CRPA) are rare in the United States. An outbreak of KPC-CRPA was investigated in Texas using molecular and epidemiologic methods and 17 cases of KPC-CRPA were identified. The isolates were genetically related and harbored the emerging P. aeruginosa multilocus sequence type 235, the first in the United States.


2020 ◽  
Vol 7 (9) ◽  
Author(s):  
Saima Aslam ◽  
Elizabeth Lampley ◽  
Darcy Wooten ◽  
Maile Karris ◽  
Constance Benson ◽  
...  

Abstract Background Due to increasing multidrug-resistant (MDR) infections, there is an interest in assessing the use of bacteriophage therapy (BT) as an antibiotic alternative. After the first successful case of intravenous BT to treat a systemic MDR infection at our institution in 2017, the Center for Innovative Phage Applications and Therapeutics (IPATH) was created at the University of California, San Diego, in June 2018. Methods We reviewed IPATH consult requests from June 1, 2018, to April 30, 2020, and reviewed the regulatory process of initiating BT on a compassionate basis in the United States. We also reviewed outcomes of the first 10 cases at our center treated with intravenous BT (from April 1, 2017, onwards). Results Among 785 BT requests to IPATH, BT was administered to 17 of 119 patients in whom it was recommended. One-third of requests were for Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium abscessus. Intravenous BT was safe with a successful outcome in 7/10 antibiotic-recalcitrant infections at our center (6 were before IPATH). BT may be safely self-administered by outpatients, used for infection suppression/prophylaxis, and combined successfully with antibiotics despite antibiotic resistance, and phage resistance may be overcome with new phage(s). Failure occurred in 2 cases despite in vitro phage susceptibility. Conclusions We demonstrate the safety and feasibility of intravenous BT for a variety of infections and discuss practical considerations that will be critical for informing future clinical trials.


2019 ◽  
Vol 95 (2) ◽  
pp. 212-215 ◽  
Author(s):  
James A. Karlowsky ◽  
Sibylle H. Lob ◽  
Katherine Young ◽  
Mary R. Motyl ◽  
Daniel F. Sahm

2000 ◽  
Vol 38 (4) ◽  
pp. 1581-1586 ◽  
Author(s):  
D. L. Baggesen ◽  
D. Sandvang ◽  
F. M. Aarestrup

A total of 136 isolates of Salmonella enterica serovar Typhimurium DT104 from Denmark (n = 93), Germany (n = 10), Italy (n = 4), Spain (n = 5), and the United Kingdom (n = 9) were characterized by antimicrobial resistance analysis, plasmid profiling, pulsed-field gel electrophoresis (PFGE) with the restriction enzymes XbaI and BlnI, and analysis for the presence of integrons and antibiotic resistance genes. The isolates from Denmark were from nine pig herds, while the isolates from other countries were both of animal and of human origin. All but 10 isolates were resistant to ampicillin, chloramphenicol, spectinomycin, streptomycin, sulfonamides, and tetracycline. Five isolates from the United Kingdom and Spain were sensitive to all antibiotics examined, whereas four isolates from the United Kingdom and the United States were also resistant to one or more of the antibiotics, namely, gentamicin, neomycin, and trimethoprim. All but two strains had the same PFGE profiles when the XbaI restriction enzyme was used, while seven different profiles were observed when theBlnI restriction enzyme was used. Different dominatingBlnI types were observed among European isolates compared with the types observed among those from the United States. All the isolates harbored common 95-kb plasmids either alone or in combination with smaller plasmids, and a total of 11 different plasmid profiles were observed. Furthermore, all but one of the multidrug-resistant isolates contained two integrons, ant (3")-Ia andpse-1. Sensitive isolates contained no integrons, and isolates that were resistant to spectinomycin, streptomycin, and sulfonamides had only one integron containing ant (3")-Ia. When restriction enzyme BlnI was used, the 14 isolates from one of the nine herds in Denmark showed unique profiles, whereas isolates from the remaining herds were homogeneous. Among isolates from seven of nine herds, the same plasmid profile (95 kb) was observed, but isolates from two herds had different profiles. Thus, either PFGE (withBlnI) or plasmid profiling could distinguish isolates from three of nine pig herds in Denmark. The epidemiological markers (antimicrobial susceptibility testing, plasmid profiling, and PFGE) applied demonstrated high in vivo stability in the Danish herds. This may indicate that some different strains of multidrug-resistantS. enterica serovar Typhimurium DT104 have been introduced into Danish food animal herds. The presence of isolates from six different countries with similar profiles by PFGE with XbaI and highly homogeneous profiles by PFGE with BlnI indicate that multidrug-resistant S. enterica serovar Typhimurium DT104 has probably been spread clonally in these countries. However, some minor variation could be observed by using plasmid profiling and profiling by PFGE with BlnI. Thus, a more sensitive technique for subtyping of strains of DT104 and a broader investigation may help in elucidating the epidemiological spread of DT104 in different parts of the world.


2020 ◽  
Vol 2 (2) ◽  
pp. 69-76
Author(s):  
Dini Aulia Azmi ◽  
Nurlailah Nurlailah ◽  
Ratih Dewi Dwiyanti

Streptococcus pyogenes and Pseudomonas aeruginosa are some of the causes of infectious diseases. Centella asiatica (L.) Urban has many benefits for humans, including overcoming fever, anti-bacterial, and anti-inflammatory. This study aims to determine the inhibition of Centella asiatica (L.) Urban leaves ethanol extract on the growth of Streptococcus pyogenes and Pseudomonas aeruginosa. This research is the initial stage of the development of herbal medicines to treat Streptococcus pyogenes and Pseudomonas aeruginosa infections. The independent variable was the concentration of ethanol extract of Centella asiatica (L.) Urban leaves and the dependent variable was the growth of Streptococcus pyogenes and Pseudomonas aeruginosa. The anti-bacterial activity test was carried out by the liquid dilution method. The concentrations used are 20%, 40%, 60%, 80%. 100% The results showed that the minimum inhibitory concentration (MIC) against Streptococcus pyogenes: 40% and Pseudomonas aeruginosa: 40%. Minimum bactericidal concentration (MBC) results for Streptococcus pyogenes: 60% and Pseudomonas aeruginosa: 60%. So it can be concluded that there is inhibition of the ethanol extract of Centella asiatica (L.) Urban leaves on the growth of Streptococcus pyogenes and Pseudomonas aeruginosa. Centella Asiatica (L.) Urban extract has potential as herbal medicine against bacterial infections but requires further research to determine its effect in vivo.


2020 ◽  
Vol 41 (S1) ◽  
pp. s305-s305
Author(s):  
Karoline Sperling ◽  
Amy Priddy ◽  
Nila Suntharam ◽  
Adam Karlen

Background: With increasing medical tourism and international healthcare, emerging multidrug resistant organisms (MDROs) or “superbugs” are becoming more prevalent. These MDROs are unique because they are resistant to antibiotics and can carry special resistance mechanisms. In April 2019, our hospital was notified that a superbug, New Delhi Metallo-β-lactamase(NDM)–producing carbapenem-resistant Enterobacteriaceae (CRE), was identified in a patient who had been transferred to another hospital after being at our hospital for 3 weeks. Our facility had a CRE admission screening protocol in place since 2013, but this patient did not meet the criteria to be screened on admission. Methods: The infection prevention (IP) team consulted with the Minnesota Department of Health (MDH) and gathered stakeholders to discuss containment strategies using the updated 2019 CDC Interim Guidance for Public Health Response to Contain Novel or Targeted Multidrug-resistant Organisms (MDROs) to determine whether transmission to other patients had occurred. NDM CRE was classified under tier 2 organisms, meaning those primarily associated with healthcare settings and not commonly identified in the region, and we used this framework to conduct an investigation. A point-prevalence study was done in an intensive care unit that consisted of rectal screening of 7 patients for both CRE and Candida auris, another emerging MDRO. These swabs were sent to the Antibiotic Resistance Laboratory Network (ARLN) Central Regional Lab at MDH for testing. An on-site infection control risk assessment was done by the MDH Infection Control Assessment and Response (ICAR) team. Results: All 7 patients were negative for both CRE and C. auris, and no further screening was done. During the investigation, it was discovered that the patient had had elective ambulatory surgery outside the United States in March 2019. The ICAR team assessment provided overall positive feedback to the nursing unit about isolation procedures, cleaning products, and hand hygiene product accessibility. Opportunities included set-up of soiled utility room and updating our process to the 2019 MDH recommendation to screen patients for CRE and C. auris on admission who have been hospitalized, had outpatient surgery, or hemodialysis outside the United States in the previous year. Conclusions: Point-prevalence study results showed no transmission of CRE and highlighted the importance of standard precautions. This event supports the MDH recommendation to screen for CRE any patients who have been hospitalized, had outpatient surgery, or had hemodialysis outside the United States in the previous year.Funding: NoneDisclosures: None


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S195-S195
Author(s):  
Naeemah Z Logan ◽  
Beth E Karp ◽  
Kaitlin A Tagg ◽  
Claire Burns-Lynch ◽  
Jessica Chen ◽  
...  

Abstract Background Multidrug-resistant (MDR) Shigella sonnei infections are a serious public health threat, and outbreaks are common among men who have sex with men (MSM). In February 2020, Australia’s Department of Health notified CDC of extensively drug-resistant (XDR) S. sonnei in 2 Australian residents linked to a cruise that departed from Florida. We describe an international outbreak of XDR S. sonnei and report on trends in MDR among S. sonnei in the United States. Methods Health departments (HDs) submit every 20th Shigella isolate to CDC’s National Antimicrobial Resistance Monitoring System (NARMS) laboratory for susceptibility testing. We defined MDR as decreased susceptibility to azithromycin (MIC ≥32 µg/mL) with resistance to ampicillin, ciprofloxacin, and cotrimoxazole, and XDR as MDR with additional resistance to ceftriaxone. We used PulseNet, the national subtyping network for enteric disease surveillance, to identify US isolates related to the Australian XDR isolates by short-read whole genome sequencing. We screened these isolates for resistance determinants (ResFinder v3.0) and plasmid replicons (PlasmidFinder) and obtained patient histories from HDs. We used long-read sequencing to generate closed plasmid sequences for 2 XDR isolates. Results NARMS tested 2,781 S. sonnei surveillance isolates during 2011–2018; 80 (2.9%) were MDR, including 1 (0.04%) that was XDR. MDR isolates were from men (87%), women (9%), and children (4%). MDR increased from 0% in 2011 to 15.3% in 2018 (Figure). In 2020, we identified XDR isolates from 3 US residents on the same cruise as the Australians. The US residents were 41–42 year-old men; 2 with available information were MSM. The US and Australian isolates were highly related (0–1 alleles). Short-read sequence data from all 3 US isolates mapped to the blaCTX-M-27 harboring IncFII plasmids from the 2 Australian isolates with >99% nucleotide identity. blaCTX-M-27 genes confer ceftriaxone resistance. Increase in Percentage of Shigella sonnei Isolates with Multidrug Resistance* in the United States, 2011–2018† Conclusion MDR S. sonnei is increasing and is most often identified among men. XDR S. sonnei infections are emerging and are resistant to all recommended antibiotics, making them difficult to treat without IV antibiotics. This outbreak illustrates the alarming capacity for XDR S. sonnei to disseminate globally among at-risk populations, such as MSM. Disclosures All Authors: No reported disclosures


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