Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.

Retrospective analysis of colistin-resistant bacteria in a tertiary care centre in India.

The incidence of carbapenem-resistant Enterobacteriaceae has been steadily rising. The morbidity, mortality and financial implications of such patients are significant. We did a retrospective analysis of the case records of 11 patients who had culture report positive for pan drug-resistant (PDR) organisms. There were total 15 isolates of PDR organisms in 11 patients. These were associated with catheter-associated urinary tract infections (7), tracheitis (4), bacteraemia (2), meningitis (1) and soft-tissue infection (1). Average APACHE II score was 23.72 (range 7-36) indicating patients with multiple co-morbidities and organ dysfunction. The average length of hospital stay was 60.72 (25-123) days. The overall mortality rate was 81.81 per cent, while PDR infection-related mortality was 18.18 per cent. Strict implementation of antibiotic stewardship programme is essential to limit use and prevent abuse of colistin.

Antimicrobial resistance among Escherichia coli isolates from dogs presented with urinary tract infections at a veterinary teaching hospital in South Africa.

BACKGROUND: This study investigated the burden and predictors of canine E. coli urinary tract infections (UTI) and antimicrobial resistance among dogs presented at a veterinary teaching hospital in South Africa, 2007-2012. METHODS: The Cochran-Armitage trend test was used to investigate temporal trends while logistic regression models were used to investigate predictors (age, sex, breed, year) of E. coli infections and antimicrobial resistance (AMR). RESULTS: A total of 22.3% (168/755) of the urinary specimens tested positive for E. coli. A significant (p = 0.0004) decreasing temporal trend in the percentage of E. coli positive isolates was observed over the study period. There were high levels of AMR to penicillin-G (99%), clindamycin (100%), tylosine (95%), cephalothin (84%) but relatively low levels of resistance to enrofloxacin (16%), orbifloxacin (21%). Almost all (98%, 164/167) the isolates exhibited multidrug resistance (MDR), while only 11% (19/167) and 2% (4/167) exhibited extensive drug resistance (XDR) and pan-drug resistance (PDR), respectively. CONCLUSIONS: Although, the risk of E. coli UTI declined during the study period, the risk of AMR increased. The high levels of AMR and MDR as well as the presence of XDR and PDR is concerning as these have the potential of affecting prognosis of UTI treatments.

The challenges of multi-drug-resistance in hepatology.

Antimicrobial resistance has become a major global public health security problem that needs coordinated approaches at regional, national and international levels. Antibiotic overuse and the failure of control measures to prevent the spread of resistant bacteria in the healthcare environment have led to an alarming increase in the number of infections caused by resistant bacteria, organisms that resist many (multi-drug and extensively drug-resistant strains), if not all (pan-drug-resistant bacteria) currently available antibiotics. While Gram-positive cocci resistance (methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci) shows a heterogeneous geographical distribution, extended-spectrum ß-lactamase-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae have become pandemic worldwide and endemic in some parts of the world, respectively. Moreover, currently available therapeutic options for resistant bacteria are very limited, with very few new agents in development. Antimicrobial resistance is especially relevant in decompensated cirrhosis. Firstly, cirrhotic patients are highly susceptible to develop infections caused by resistant bacteria as risk factors of multiresistance concentrate in this population (mainly repeated hospitalizations and antibiotic exposure). Secondly, inappropriate empirical antibiotic schedules easily translate into increased morbidity (acute kidney injury, acute-on-chronic liver failure, septic shock) and hospital mortality in advanced cirrhosis. Therefore, hepatologists must face nowadays a complex clinical scenario that requires new empirical antibiotic strategies that may further spread resistance. Global, regional and local preventive measures should therefore be implemented to combat antimicrobial resistance in cirrhosis including the restriction of antibiotic prophylaxis to high-risk populations, investigation on non-antibiotic prophylaxis, stewardship programs on adequate antibiotic prescription and on increasing awareness of the problem among health professionals, and well-defined early de-escalation policies based on rapid microbiological diagnostic tests. Other infection control practices such as hand hygiene and barrier precautions are also important. Clinical impact and cost-effectiveness of epidemiological surveillance programs (periodic rectal and nasal swabs) should also be explored.

Extensively and pan-drug resistant Pseudomonas aeruginosa keratitis: clinical features, risk factors, and outcome.

BACKGROUND: Emergence of multi-drug resistant (MDR), extensively drug resistant (XDR), and pan-drug resistant (PDR) strains of Pseudomonas aeruginosa pose a significant therapeutic challenge. Managing XDR and PDR Pseudomonas aeruginosa keratitis would be extremely difficult due to paucity of safe and effective topical medications. We aim to describe the clinical features, risk factors, and outcome of XDR and PDR Pseudomonas aeruginosa keratitis. METHODS: A retrospective chart review of consecutive cases of XDR and PDR Pseudomonas aeruginosa keratitis were identified from Ocular Microbiology Department. XDR and PDR were defined based on criteria established by Centers for Disease Control and European Centre for Disease Prevention and Control. The following data was collected: age, gender, occupation, symptom duration, systemic and ocular risk factors, infiltrate characteristics, antimicrobial susceptibility, complications, surgical interventions, presenting, and final visual acuity and final outcome. Complete success was defined as resolution of the infiltrate with scar formation on medical treatment alone. Partial success was the resolution following tissue adhesive application. Failure was an inadequate response to medical therapy with progressive increase in infiltrate, corneal melting, and/or perforation necessitating one or more therapeutic penetrating keratoplasties or evisceration. RESULTS: Fifteen eyes of 13 patients were included. Seven (53.8 %) were male with left eye involvement in nine (60 %) cases. Most common risk factors were bandage contact lens (6, 40 %), topical steroids (5, 33.3 %), previous therapeutic graft (4, 26.6 %), and ocular surface disorder (OSD) following Stevens Johnson Syndrome (SJS) (4, 26.6 %). Of 15 isolates, six (40 %) were sensitive only to imipenem, three (20 %) to colistin, two (13.3 %) to neomycin, one (6.7 %) each to imipenem and colistin, imipenem and ceftazidime, and azithromycin respectively. One isolate was resistant to all antibiotics. Complete success was noted in two (16.67 %), partial success in three (25 %) and failure in seven (58.33 %) eyes. Five (33.3 %) eyes healed on imipenem (three eyes), azithromycin (one eye), and imipenem and colistin (one eye). CONCLUSION: XDR and PDR Pseudomonas aeruginosa keratitis are extremely difficult to treat. Globe salvage was possible in all cases; however, more than half required therapeutic grafts. Close monitoring of patients with known ocular and systemic factors is warranted.

Characterization and genomic analysis of novel bacteriophage NK20 to revert colistin resistance and combat pandrug-resistant Klebsiella pneumoniae in a rat respiratory infection model.

AIM: We investigated the therapeutic capacity of the isolated Klebsiella bacteriophage NK20 against pandrug-resistant strains. Moreover, we assessed the impact of resistance development on the overall therapeutic outcome both in vitro and in vivo. MAIN METHODS: The pandrug-resistant K. pneumoniae Kp20 is used as a host strain for the isolation of bacteriophages using sewage samples. Spot assay was then used to compare the spectra of the isolated phages, while kinetic and genomic analysis of the phage with the broadest spectrum was assessed. Antibacterial potential of the phage was assessed using turbidimetric assay and MIC with and without colistin. Finally, the therapeutic efficacy was evaluated in vivo using a rat respiratory infection model. KEY FINDINGS: The isolated lytic bacteriophage (NK20) showed a relatively broad spectrum and an acceptable genomic profile. In vitro antibacterial assay revealed bacterial resistance development after 12 h. Colistin inhibited bacterial regrowth and reduced pandrug-resistant strains' colistin MICs. Despite the isolation of resistant clones, intranasal administration of NK20 significantly (p < 0.05) reduced the bacterial load in both the pulmonary and blood compartments and rescued 100 % of challenged rats. Histological and immunological analysis of treated animals' lung tissue revealed less inflammation and lower TNF-α and caspase-3 expression. SIGNIFICANCE: NK20 is a promising candidate that rescued rats from untreatable, pan-drug-resistant K. pneumoniae Kp20. Moreover, it steers the evolution of resistant mutants with higher sensitivity to colistin and less virulence, opening the door for using phages as sensitizing and anti-virulence entities rather than direct killer.

Clinical Management of a Pandrug-Resistant OXA-48 Klebsiella pneumoniae Infection in the Pediatric Intensive Care Unit.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the serious forms of health care-associated infection. Pan-drug resistant (PDR) CRKP infections can cause severe infections. Mortality and treatment costs in the pediatric intensive care unit (PICU) are high. This study aims to share our experience regarding the treatment of oxacillinase (OXA)-48-positive PDR-CRKP infection in our 20-bed tertiary PICU with isolated rooms and 1 nurse for every 2-3 patients. Methods: Patient demographic characteristics, underlying diseases, previous infections, source of infection PDR-CRKP, treatment modalities, measures used, and outcomes were recorded. Findings: Eleven patients (eight men and three women) were found to have PDR OXA-48-positive CRKP. Because of the simultaneous detection of PDR-CRKP in three patients and the rapid spread of the disease, it was classified as a clinical outbreak, and strict infection control measures were taken. Combination therapy with double carbapenemase (meropenem and imipenem), amikacin, colistin, and tigecycline was used for treatment. The mean duration of treatment and isolation was 15.7 and 65.4 days, respectively. No treatment-related complication was observed, only one patient died, and the mortality rate was 9%. Conclusions: This severe clinical outbreak can be successfully treated with effective treatment with combined antibiotics and strict adherence to infection control measures. ClinicalTrial.gov ID: 28/01/2022 - 1/5.

The menace of colistin resistance across globe: Obstacles and opportunities in curbing its spread.

Colistin-resistance in bacteria is a big concern for public health, since it is a last resort antibiotic to treat infectious diseases of multidrug resistant and carbapenem resistant Gram-negative pathogens in clinical settings. The emergence of colistin resistance in aquaculture and poultry settings has escalated the risks associated with colistin resistance in environment as well. The staggering number of reports pertaining to the rise of colistin resistance in bacteria from clinical and non-clinical settings is disconcerting. The co-existence of colistin resistant genes with other antibiotic resistant genes introduces new challenges in combatting antimicrobial resistance. Some countries have banned the manufacture, sale and distribution of colistin and its formulations for food producing animals. However, to tackle the issue of antimicrobial resistance, a one health approach initiative, inclusive of human, animal, and environmental health needs to be developed. Herein, we review the recent reports in colistin resistance in bacteria of clinical and non-clinical settings, deliberating on the new findings obtained regarding the development of colistin resistance. This review also discusses the initiatives implemented globally in mitigating colistin resistance, their strength and weakness.

Identification and Characterization of vB_PreP_EPr2, a Lytic Bacteriophage of Pan-Drug Resistant Providencia rettgeri.

Providencia rettgeri is an emerging opportunistic Gram-negative pathogen with reports of increasing antibiotic resistance. Pan-drug resistant (PDR) P. rettgeri infections are a growing concern, demonstrating a need for the development of alternative treatment options which is fueling a renewed interest in bacteriophage (phage) therapy. Here, we identify and characterize phage vB_PreP_EPr2 (EPr2) with lytic activity against PDR P. rettgeri MRSN 845308, a clinical isolate that carries multiple antibiotic resistance genes. EPr2 was isolated from an environmental water sample and belongs to the family Autographiviridae, subfamily Studiervirinae and genus Kayfunavirus, with a genome size of 41,261 base pairs. Additional phenotypic characterization showed an optimal MOI of 1 and a burst size of 12.3 ± 3.4 PFU per bacterium. EPr2 was determined to have a narrow host range against a panel of clinical P. rettgeri strains. Despite this fact, EPr2 is a promising lytic phage with potential for use as an alternative therapeutic for treatment of PDR P. rettgeri infections.

First Detection of Extensively Drug-Resistant Salmonella Typhi Isolates Harboring VIM and GES Genes for Carbapenem Resistance from Faisalabad, Pakistan.

Rapid emergence of resistance in Salmonella enterica serovar Typhi (Salmonella Typhi) against most of the available therapeutic options for typhoid has rendered its treatment more difficult. This study sought to determine the current scenario of antimicrobial resistance in local isolates of Faisalabad following several treatment failure reports. Out of 300 clinical specimens collected in 2018, 45 isolates were identified as Salmonella Typhi. To assess changes, we compared their antibiogram profile with 31 Salmonella Typhi strains isolated in 2005. The isolates collected during 2018 showed a significant rise in antimicrobial drug resistance as compared with isolates revived from the cultures of 2005, including 15 multidrug-resistant (MDR), 20 extensively drug-resistant, and 14 pan drug-resistant isolates compared with only 8 MDRs from 2005. Notably, in 2018 isolates, resistance to azithromycin was seen in 75% of the isolates. Extended-spectrum beta-lactamase production was detected in 47% of Salmonella Typhi isolates and 18% isolates showed resistance against carbapenems. The sequences of two carbapenemase genes, VIM and GES, found in Salmonella Typhi were submitted in NCBI. The carbapenem resistance is rare in Enterobacteriaceae and probably first time reported in Salmonella Typhi. H58 haplotype was identified in the 2018 Salmonella Typhi isolates and PCR-restriction fragment length polymorphism method identified 16.7% of H58 strains that belonged to lineage I, 19.4% of H58 strains that belonged to lineage II, and the remaining 63.9% that belonged to the node. The regional difference in the antimicrobial resistance trend needs effective epidemiological studies.

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey.

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.

A Systematic Review of Antibiotic Resistance Trends and Treatment Options for Hospital-Acquired Multidrug-Resistant Infections.

Antimicrobial resistance is a major public health challenge described by the World Health Organization as one of the top 10 public health challenges worldwide. Drug-resistant microbes contribute significantly to morbidity and mortality in the hospital, especially in the critical care unit. The primary etiology of increasing antibiotic resistance is inappropriate and excessive use of antibiotics. The alarming rise of drug-resistant microbes worldwide threatens to erode our ability to treat infections with our current armamentarium of antibiotics. Unfortunately, the pace of development of new antibiotics by the pharmaceutical industry has not kept up with rising resistance to expand our options to treat microbial infections. The costs of antibiotic resistance include death and disability, extended hospital stays due to prolonged sickness, need for expensive therapies, rising healthcare expenditure, reduced productivity from time out of the workforce, and rising penury. This review sums up the common mechanisms, trends, and treatment options for hospital-acquired multidrug-resistant microbes.

Molecular Mechanisms of Colistin Resistance in Klebsiella pneumoniae in a Tertiary Care Teaching Hospital.

Background: Over the last two decades, the prevalence of colistin resistance among the members of Enterobacteriaceae has been increasing, particularly among Klebsiella pneumoniae isolates; this limits the potential use of colistin and leads to worsened clinical outcomes. Methods: We investigated the prevalence and genetic characteristics of colistin-resistant K. pneumoniae (COLR-KP) in clinical isolates using genomic sequencing. Results: In total, 53 K. pneumoniae isolates (4.5%, 53/1,171) were confirmed as COLR-KP, of which eight isolates carried mobile colistin-resistant (mcr) gene. Although the overall prevalence rate (0.7%, 8/1,171) of mcr-like genes in clinical K. pneumoniae remained relatively low, the presence of mcr (15.1%, 8/53) among the COLR-KP isolates indicated that the mobile resistance gene was already widespread among K. pneumoniae isolates in hospital setting. We randomly selected 13 COLR-KP isolates (four mcr-bearing and nine non-mcr-bearing isolates) for whole-genome sequencing, including two pandrug-resistant and four sequence type 11 (ST11) isolates. Phylogenetic analysis revealed that all COLR-KP isolates were genetically diverse. Among the four mcr-bearing isolates, three (KP4, KP18, and KP30) were positive for mcr-1 and one (KP23) for mcr-8; none of the other mcr genes were detected. The mcr-1 in the KP4 and KP30 isolates were located in an IncX4 plasmid (approximately 33 kb) and could be successfully transferred to Escherichia coli J53AZR. In contrast, for the mcr-8-bearing plasmid in KP23 (IncFII), colistin resistance could not be transferred by conjugation. The mcr-1-producing isolate KP18 coexists a novel plasmid-carried tigecycline resistance gene tmexCD1-toprJ1. The most common chromosomal mutation associated with colistin resistance was a T246A amino acid substitution in PmrB, which was identified in most COLR-KP isolates (11/13, 84.6%). All ST11 isolates additionally had an R256G amino acid substitution. Critical virulence factors associated with hypervirulent K. pneumoniae were detected in four COLR-KP isolates; these virulence factors included aerobactin, salmochelin, and yersiniabactin. Conclusion: We found that mcr-bearing COLR-KP emerged in our hospital and was growing at an increasing rate. Simultaneous emergence of hypervirulence and colistin-tigecycline-carbapenem resistance in the epidemic clone ST11 K. pneumoniae was also observed; this highlights the significance of active and continuous surveillance.

Characteristics of Asymptomatic Bacteriuria in Diabetes Mellitus Patients: A Retrospective Observational Study.

Background and objective The term asymptomatic bacteriuria (ASB) refers to the isolation of bacteria in a urine specimen of individuals without any symptoms of urinary tract infection (UTI). Diabetes mellitus (DM) is a disease involving multiple organ systems, characterized by its chronicity and hence endless complications including ASB. This study aimed to determine the characteristics of ASB and antibiotic susceptibility patterns among patients with diabetes. Materials and methods This was a retrospective observational study conducted in a tertiary care hospital. The study included patients with a diagnosis of diabetes with no signs and symptoms of UTI but who still showed the growth of an organism in urine culture. A total of 222 urine cultures were analyzed retrospectively, ensuring that they met the inclusion criteria through non-probability consecutive sampling. Results The mean age of the study participants was 62.89 ± 13.77 years; 76% of them were females, and 61% had a family history of diabetes. The most frequent organisms isolated were Escherichia coli (E. coli), Enterococcus, Klebsiella pneumonia, Pseudomonas aeruginosa, and Enterobacter species. A total of 20 subjects had dual bacterial growth in their cultures, with Enterococcus species (n=17) being the most common organism. Gender, family history of diabetes, levels of hemoglobin A1c (HbA1c), and advanced age were all found significantly associated with ASB. Conclusion Our study is the first of its kind to analyze and examine the risk factors associated with ASB in DM patients, and to identify the pathogens involved, along with assessing their antibiotic resistance profiles.

Rare but Fatal Case of Cavitary Pneumonia Caused by Alcaligenes Faecalis.

Alcaligenes faecalis is a gram-negative bacterium that is commonly found in the environment. This pathogen is usually transmitted in the form of droplets through ventilation equipment and nebulizers, but transmission through direct contact has also been documented in few case reports. This pathogen can cause rare but fatal infections including appendicitis, abscesses, meningitis, bloodstream infection, endocarditis, and post-operative endophthalmitis. Pan drug resistance to all commercially available antibiotics has been emerging globally. We present the case of a 66-year-old male who had respiratory failure along with multiple comorbidities. A large cavitary lesion caused by pan drug-resistant Alcaligenes faecalis was found on chest imaging. Despite the treatment with broad-spectrum antibiotics, the clinical outcome was very poor.

Pan-Drug Resistant Acinetobacter baumannii, but Not Other Strains, Are Resistant to the Bee Venom Peptide Mellitin.

Acinetobacter baumannii is a prevalent pathogen in hospital settings with increasing importance in infections associated with biofilm production. Due to a rapid increase in its drug resistance and the failure of commonly available antibiotics to treat A. baumannii infections, this bacterium has become a critical public health issue. For these multi-drug resistant A. baumannii, polymyxin antibiotics are considered the only option for the treatment of severe infections. Concerning, several polymyxin-resistant A. baumannii strains have been isolated over the last few years. This study utilized pan drug-resistant (PDR) strains of A. baumannii isolated in Brazil, along with susceptible (S) and extreme drug-resistant (XDR) strains in order to evaluate the in vitro activity of melittin, an antimicrobial peptide, in comparison to polymyxin and another antibiotic, imipenem. From a broth microdilution method, the determined minimum inhibitory concentration showed that S and XDR strains were susceptible to melittin. In contrast, PDR A. baumannii was resistant to all treatments. Treatment with the peptide was also observed to inhibit biofilm formation of a susceptible strain and appeared to cause permanent membrane damage. A subpopulation of PDR showed membrane damage, however, it was not sufficient to stop bacterial growth, suggesting that alterations involved with antibiotic resistance could also influence melittin resistance. Presumably, mutations in the PDR that have arisen to confer resistance to widely used therapeutics also confer resistance to melittin. Our results demonstrate the potential of melittin to be used in the control of bacterial infections and suggest that antimicrobial peptides can serve as the basis for the development of new treatments.

First Report of aacC5-aadA7Δ4 Gene Cassette Array and Phage Tail Tape Measure Protein on Class 1 Integrons of Campylobacter Species Isolated from Animal and Human Sources in Egypt.

Campylobacter species are common commensals in the gastrointestinal tract of livestock animals; thus, animal-to-human transmission occurs frequently. We investigated for the first time, class 1 integrons and associated gene cassettes among pan drug-resistant (PDR), extensively drug-resistant (XDR), and multidrug-resistant (MDR) Campylobacter species isolated from livestock animals and humans in Egypt. Campylobacter species were detected in 58.11% of the analyzed chicken samples represented as 67.53% Campylobacter jejuni(C. jejuni) and 32.47% Campylobacter coli (C. coli). C. jejuni isolates were reported in 51.42%, 74.28%, and 66.67% of examined minced meat, raw milk, and human stool samples, respectively. Variable antimicrobial resistance phenotypes; PDR (2.55%), XDR (68.94%), and MDR (28.5%) campylobacters were reported. Molecular analysis revealed that 97.36% of examined campylobacters were integrase gene-positive; all harbored the class 1 integrons, except one possessed an empty integron structure. DNA sequence analysis revealed the predominance of aadA (81.08%) and dfrA (67.56%) alleles accounting for resistance to aminoglycosides and trimethoprim, respectively. This is the first report of aacC5-aadA7Δ4 gene cassette array and a putative phage tail tape measure protein on class 1 integrons of Campylobacter isolates. Evidence from this study showed the possibility of Campylobacter-bacteriophage interactions and treatment failure in animals and humans due to horizontal gene transfer mediated by class 1 integrons.

Prevalence and Predictors of Antimicrobial Resistance Among Enterococcus spp. From Dogs Presented at a Veterinary Teaching Hospital, South Africa.

Background: While surveillance of antimicrobial drug resistance is ongoing in human medicine in South Africa, there is no such activity being performed in veterinary medicine. As a result, there is a need to investigate antimicrobial resistance among enterococci isolated from dogs in South Africa to improve understanding of the status of antimicrobial drug resistance given its public and veterinary public health importance. This study investigated antimicrobial resistance and factors associated with resistance profiles of enterococci isolated from dogs presented for veterinary care at a veterinary teaching hospital in South Africa. Methods: In total 102 Enterococcus isolated between 2007 and 2011 by a bacteriology laboratory at a teaching hospital were included in this study. Antimicrobial susceptibility of the isolates was determined against a panel of 18 antimicrobials using the Kirby Bauer disc diffusion technique. Univariate analysis was used to assess simple associations between year, season, breed group, age group, sex, and specimen as covariates and extensive drug resistance (XDR) as the outcome. Variables that were significant in the univariate analysis at a generous p-value ≤ 0.2 were included in the multivariable logistic models to investigate predictors of XDR. Results: All the Enterococcus isolates were resistant to at least one antimicrobial. High proportions of isolates were resistant against lincomycin (93%), kanamycin (87%), orbifloxacin (85%), and aminogycoside-lincosamide (77%). Ninety three percent (93%), 35.3, and 8.8% of the isolates exhibited multi-drug, extensive-drug and pan-drug resistance, respectively. Only year was significantly (p = 0.019) associated with extensive-drug resistance. Conclusion: Given the zoonotic potential of Enterococcus spp., the high antimicrobial resistance and multi-drug resistance observed in this study are a public health concern from one health perspective. The identified resistance to various antimicrobials may be useful in guiding clinicians especially in resource scarce settings where it is not always possible to perform AST when making treatment decisions.

Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics.

Bacterial infections involving antibiotic-resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR), extensive-drug resistant (XDR) or pan-drug resistant (PDR) bacterial strains. Most recently, plasmid-mediated resistance to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR, XDR and PDR gram-negative bacteria has been reported. Plasmid-mediated colistin resistant gram-negative bacteria have been described to be PDR, implying a state devoid of alternative antibiotic therapeutic options. This review concisely describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and discusses the potential role of high-throughput sequencing technologies, genomics, and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antibiotic resistance as a whole.

Effect of N-acetyl cysteine, rifampicin, and ozone on biofilm formation in pan-resistant Klebsiella pneumoniae: an experimental study

ABSTRACT BACKGROUND: To the best of our knowledge, this is the first study to evaluate the effectiveness of specific concentrations of antibiofilm agents, such as N-acetyl cysteine (NAC), rifampicin, and ozone, for the treatment of pan-resistant Klebsiella pneumoniae (PRKp). OBJECTIVES: We evaluated the effectiveness of antibiofilm agents, such as NAC, rifampicin, and ozone, on biofilm formation in PRKp at 2, 6, 24, and 72 h. DESIGN AND SETTING: This single-center experimental study was conducted on June 15, 2017, and July 15, 2018, at Istanbul Faculty of Medicine, Istanbul University, Turkey. METHODS: Biofilm formation and the efficacy of these agents on the biofilm layer were demonstrated using colony counting and laser-screened confocal microscopy. RESULTS: NAC at a final concentration of 2 μg/mL was administered to bacteria that formed biofilms (24 h), and no significant decrease was detected in the bacterial counts of all isolates (all P > 0.05). Rifampicin with a final concentration of 0.1 μg/mL was administered to bacteria that formed biofilm (24 h), and no significant decrease was detected in bacterial count (all P > 0.05). Notably, ozonated water of even 4.78 mg/L concentration for 72 h decreased the bacterial count by ≥ 2 log10. CONCLUSION: Different approaches are needed for treating PRKp isolates. We demonstrate that PRKp isolates can be successfully treated with higher concentrations of ozone.