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BioRxiv : the Preprint Server For... May 2024Treatment of pulmonary disease requires multiple antibiotics including intravenous β-lactams (e.g., imipenem, meropenem). produces a β-lactamase (Bla) that...
Treatment of pulmonary disease requires multiple antibiotics including intravenous β-lactams (e.g., imipenem, meropenem). produces a β-lactamase (Bla) that inactivates β-lactam drugs but less efficiently carbapenems. Due to intrinsic and acquired resistance in and poor clinical outcomes, it is critical to understand the development of antibiotic resistance both within the host and in the setting of outbreaks. We compared serial longitudinally collected subsp. isolates from the index case of a CF center outbreak and four outbreak-related strains. We found strikingly high imipenem resistance in the later patient isolates, including the outbreak strain (MIC >512 μg/ml). The phenomenon was recapitulated upon exposure of intracellular bacteria to imipenem. Addition of the β-lactamase inhibitor avibactam abrogated the resistant phenotype. Imipenem resistance was caused by an increase in β-lactamase activity and increased mRNA level. Concurrent increase in transcription of preceding gene indicated upregulation of the entire operon in the resistant strains. Deletion of the porin coincided with the first increase in MIC (from 8 to 32 μg/ml). A frameshift mutation in responsible for the rough colony morphology, and a SNP in ATP-dependent helicase co-occurred with the second increase in MIC (from 32 to 256 μg/ml). Increased Bla expression and enzymatic activity may have been due to altered regulation of the operon by the mutated HrpA alone, or in combination with other genes described above. This work supports using carbapenem/β-lactamase inhibitor combinations for treating , particularly imipenem resistant strains.
PubMed: 38903073
DOI: 10.1101/2024.05.08.593223 -
BMC Microbiology Jun 2024In Addis Ababa, Ethiopia, open ditches along innner roads in residential areas serve to convey domestic wastewater and rainwater away from residences. Contamination of...
BACKGROUND
In Addis Ababa, Ethiopia, open ditches along innner roads in residential areas serve to convey domestic wastewater and rainwater away from residences. Contamination of drinking water by wastewater through faulty distribution lines could expose households to waterborne illnesses. This prompted the study to assess the microbiological safety of wastewater and drinking water in Addis Ababa, identify the pathogens therein, and determine their antibiotic resistance patterns.
RESULTS VIBRIO CHOLERAE
O1, mainly Hikojima serotype, was isolated from 23 wastewater and 16 drinking water samples. Similarly, 19 wastewater and 10 drinking water samples yielded Escherichia coli O157:H7. V. cholerae O1 were 100% resistant to the penicillins (Amoxacillin and Ampicillin), and 51-82% were resistant to the cephalosporins. About 44% of the V. cholerae O1 isolates in this study were Extended Spectrum Beta-Lactamase (ESBL) producers. Moreover, 26% were resistant to Meropenem. Peperacillin/Tazobactam was the only effective β-lactam antibiotic against V. cholerae O1. V. cholerae O1 isolates showed 37 different patterns of multiple resistance ranging from a minimum of three to a maximum of ten antimicrobials. Of the E. coli O157:H7 isolates, 71% were ESBL producers. About 96% were resistant to Ampicillin. Amikacin and Gentamicin were very effective against E. coli O157:H7 isolates. The isolates from wastewater and drinking water showed multiple antibiotic resistance against three to eight antibiotic drugs.
CONCLUSIONS
Open ditches for wastewater conveyance along innner roads in residence areas and underground faulty municipal water distribution lines could be possible sources for V. cholerae O1 and E. coli O157:H7 infections to surrounding households and for dissemination of multiple drug resistance in humans and, potentially, the environment.
Topics: Ethiopia; Vibrio cholerae O1; Wastewater; Escherichia coli O157; Anti-Bacterial Agents; Drinking Water; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; beta-Lactamases; Humans; Water Microbiology
PubMed: 38902619
DOI: 10.1186/s12866-024-03302-8 -
BMC Infectious Diseases Jun 2024Phytobacter diazotrophicus (P. diazotrophicus) is an opportunistic pathogen that causes nosocomial outbreaks and sepsis. However, there are no reports of P....
BACKGROUND
Phytobacter diazotrophicus (P. diazotrophicus) is an opportunistic pathogen that causes nosocomial outbreaks and sepsis. However, there are no reports of P. diazotrophicus isolated from human blood in China.
CASE PRESENTATION
A 27-day-old female infant was admitted to our hospital with fever and high bilirubin levels. The clinical features included jaundice, abnormal coagulation, cholestasis, fever, convulsions, weak muscle tension, sucking weakness, ascites, abnormal tyrosine metabolism, cerebral oedema, abnormal liver function, clavicle fracture, and haemolytic anaemia. The strain isolated from the patient's blood was identified as P. diazotrophicus by whole-genome sequencing (WGS). Galactosemia type 1 (GALAC1) was diagnosed using whole-exome sequencing (WES). Based on drug sensitivity results, 10 days of anti-infective treatment with meropenem combined with lactose-free milk powder improved symptoms.
CONCLUSION
P. diazotrophicus was successfully identified in a patient with neonatal sepsis combined with galactosemia. Galactosemia may be an important factor in neonatal sepsis. This case further expands our understanding of the clinical characteristics of GALAC1.
Topics: Humans; Female; China; Galactosemias; Sepsis; Infant, Newborn; Anti-Bacterial Agents; Meropenem; Whole Genome Sequencing; Gammaproteobacteria
PubMed: 38898413
DOI: 10.1186/s12879-024-09458-y -
British Journal of Biomedical Science 2024Within cystic fibrosis microbiology, there is often mismatch between the antibiotic susceptibility result of an isolated bacterial pathogen and the clinical outcome,...
Case Report: The Conundrum of What to Pick? Antibiotic Susceptibility Variability in in Cystic Fibrosis: Implications for Antibiotic Susceptibility Testing and Treatment.
Within cystic fibrosis microbiology, there is often mismatch between the antibiotic susceptibility result of an isolated bacterial pathogen and the clinical outcome, when the patient is treated with the same antibiotic. The reasoning for this remains largely elusive. Antibiotic susceptibility to four antibiotics (ceftazidime, meropenem, minocycline and trimethoprim-sulfamethoxazole) was determined in consecutive isolates ( = 11) from an adult cystic fibrosis patient, over a 63 month period. Each isolate displayed its own unique resistotype. The first isolate was sensitive to all four antibiotics, in accordance with Clinical and Laboratory Standards Institute methodology and interpretative criteria. Resistance was first detected at four months, showing resistance to ceftazidime and meropenen and intermediate resistance to minocycline and trimethoprim-sulfamethoxazole. Pan resistance was first detected at 18 months (resistotype IV), with three resistotypes (I, II and III) preceding this complete resistotype. The bacterium continued to display further antibiotic susceptibility heterogeneity for the next 45 months, with the description of an additional seven resistotypes (resistotypes V-XI). The Relative Resistance Index of this bacterium over the 63 month period showed no relationship between the development of antibiotic resistance and time. Adoption of mathematical modelling employing multinomial distribution demonstrated that large numbers of individual colony picks (>40/sputum), would be required to be 78% confident of capturing all 11 resistotypes present. Such a requirement for large numbers of colony picks combined with antibiotic susceptibility-related methodological problems creates a conundrum in biomedical science practice, in providing a robust assay that will capture antibiotic susceptibility variation, be pragmatic and cost-effective to deliver as a pathology service, but have the reliability to help clinicians select appropriate antibiotics for their patients. This study represents an advance in biomedical science as it demonstrates potential variability in antibiotic susceptibility testing with . Respiratory physicians and paediatricians need to be made aware of such variation by biomedical scientists at the bench, so that clinicians can contextualise the significance of the reported susceptibility result, when selecting appropriate antibiotics for their cystic fibrosis patient. Furthermore, consideration needs to be given in providing additional guidance on the laboratory report to highlight this heterogeneity to emphasise the potential for misalignment between susceptibility result and clinical outcome.
Topics: Cystic Fibrosis; Humans; Anti-Bacterial Agents; Microbial Sensitivity Tests; Burkholderia cenocepacia; Burkholderia Infections; Adult; Drug Resistance, Bacterial
PubMed: 38895586
DOI: 10.3389/bjbs.2024.12749 -
Cureus May 2024Background and objective Urinary tract infections (UTIs) are a common infectious disease affecting people of various ages and genders and are prevalent in different...
The Prevalence of Multidrug-Resistant Uropathogenic Bacterial Profile With Antibiotic Susceptibility Patterns Among the Community and Hospitalized Patients During COVID Waves.
Background and objective Urinary tract infections (UTIs) are a common infectious disease affecting people of various ages and genders and are prevalent in different geographical locations. However, the way Gram-positive and Gram-negative (UTI) germs react to antibiotic treatment varies significantly. The coronavirus disease 2019 (COVID-19) pandemic has increased the frequency of secondary bacterial superinfection, leading to a spike in ongoing recommendations for antibiotic treatment, both therapeutic and preventative. In this study, we aimed to assess uropathogenic bacterial resistance and shed light on how COVID-19 epidemic waves influence the evolution of bacterial resistance. Materials and methods A cross-sectional study was conducted, assessing the different isolates of the uropathogen in all COVID-19 waves by using convenience sampling from August 2020 till the end of 2023. The VITEK-2 compact system employing industry-standard bacteriological tests to identify the bacteria and confirm their antibiotic susceptibility was utilized. Results Of the total 3877 patients, 381 (9.8%) and 3483 (89.8%) had positive and negative microbial growth, respectively. Of the 381 (9.8%) positive cases, 130 (34%) were male and 251 (65%) were female; 138 (43.3%) patients in the age range of 15-40 years developed sporadic UTIs attributed to Gram-negative bacteria. Alternatively, patients over 40 years had the highest prevalence rate (n = 180, 56.6%). The most common strains of Gram-negative and Gram-positive bacteria were and with278 (88.8%) and 13 (20.9%) cases respectively. People with Gram-negative bacteria who were not hospitalized were very resistant to trimethoprim/sulfamethoxazole (n = 219, 69.1%), cefotaxime (n = 193, 60.9%), ampicillin (n = 192, 60.6%), and amoxicillin/clavulanic acid (176, 55.5%). While high sensitivity to meropenem (n = 14, 4.4%) and imipenem (n = 13, 4.1%) was observed, hospitalized individuals had higher levels of resistance and great sensitivity to the same antibiotics. S. . were commonly present. Hospitalized patients were less sensitive to benzylpenicillin, ampicillin, and oxacillin, and there was a big rise in resistance to cefoxitin in the community. Conclusions In this study, Gram-negative germs among females were predominantly observed with extremely high multi-drug resistance (MDR). The most effective antibiotics against Gram-positive germs included linezolid, vancomycin, and nitrofurantin, while those against Gram-negative bacteria were meropenem and amikacin. Clinicians should be regularly updated and informed about antibiotic selection through routine monitoring of uropathogenic bacteria's susceptibility. Moreover, we recommend changes to the local antibiotic policy regarding the selection of UTIs; further multicentric and high-volume studies are required to gain deeper insights into the topic.
PubMed: 38894805
DOI: 10.7759/cureus.60613 -
International Journal of Molecular... May 2024The escalating threat of multidrug-resistant pathogens necessitates innovative approaches to combat infectious diseases. In this study, we examined peptides R23F*,...
The escalating threat of multidrug-resistant pathogens necessitates innovative approaches to combat infectious diseases. In this study, we examined peptides R23F*, V31K*, and R44K*, which were engineered to include an amyloidogenic fragment sourced from the S1 protein of , along with one or two cell-penetrating peptide (CPP) components. We assessed the antimicrobial efficacy of these peptides in a liquid medium against various strains of both Gram-positive bacteria, including (209P and 129B strains), MRSA (SA 180 and ATCC 43300 strains), and (strain IP 5832), and Gram-negative bacteria such as (ATCC 28753 and 2943 strains) and (MG1655 and K12 strains). Peptides R23F*, V31K*, and R44K* exhibited antimicrobial activity comparable to gentamicin and meropenem against all tested bacteria at concentrations ranging from 24 to 48 μM. The peptides showed a stronger antimicrobial effect against . Notably, peptide R44K* displayed high efficacy compared to peptides R23F* and V31K*, particularly evident at lower concentrations, resulting in significant inhibition of bacterial growth. Furthermore, modified peptides V31K* and R44K* demonstrated enhanced inhibitory effects on bacterial growth across different strains compared to their unmodified counterparts V31K and R44K. These results highlight the potential of integrating cell-penetrating peptides, amyloidogenic fragments, and amino acid residue modifications to advance the innovation in the field of antimicrobial peptides, thereby increasing their effectiveness against a broad spectrum of pathogens.
Topics: Cell-Penetrating Peptides; Antimicrobial Peptides; Microbial Sensitivity Tests; Anti-Bacterial Agents; Amino Acids; Drug Design; Amyloidogenic Proteins
PubMed: 38892216
DOI: 10.3390/ijms25116030 -
Microbiology Spectrum Jun 2024The management of infections caused by multiresistant bacteria has become of fundamental importance for any medical practice. Glycine is the most common and the simplest...
The management of infections caused by multiresistant bacteria has become of fundamental importance for any medical practice. Glycine is the most common and the simplest non-essential amino acid in humans. Glycine is very effective in improving health and supporting growth and wellbeing of humans and animals. Instead, for many bacteria, high concentrations of glycine induce lysis or deep morphological alterations. The effect of glycine on multidrug resistant (MDR) microorganisms has not yet been extensively researched. The present study was conducted 1) to establish the effect of glycine on different nosocomial pathogens isolated during routine diagnostic investigations; 2) to determine the minimum inhibitory concentration of glycine and the type of activity performed (bacteriostatic or bactericidal) on representative isolates; 3) to test the interaction between glycine and meropenem, cefiderocol, or colistin. The data reported here show a dose-dependent activity of glycine on bacteria and its bactericidal activity on MDR bacteria. Furthermore, we found that the action of glycine restores the susceptibility of multiresistant nosocomial pathogens to the tested antibiotics.IMPORTANCEAntimicrobial resistance is a constantly growing concern throughout the world, and Italy is among the Western countries where antimicrobial resistance is most widespread. In Tuscany, carbapenemase-producing are now even endemic. In this study, we challenged some resistant bacteria with a well-known molecule, glycine, the antibacterial properties of which have been known since the past century. This study could bring new insights into combining antibiotics with the simplest of all amino acids. The restoration of sensitivity to the aforementioned antibiotics by a natural compound, already used for clinical purposes, is of extreme importance in an era of proliferation of multiresistant bacteria. The use of this amino acid in evaluating its effectiveness against infections should be investigated. The low cost of this molecule can also make it easy to use even in low-income countries.
PubMed: 38888315
DOI: 10.1128/spectrum.00164-24 -
Frontiers in Cellular and Infection... 2024spp. is a genus of bacteria that is known to be closely related to . It has been debated whether should be reclassified as a subgroup of . The aim of this study is to... (Comparative Study)
Comparative Study
PURPOSE
spp. is a genus of bacteria that is known to be closely related to . It has been debated whether should be reclassified as a subgroup of . The aim of this study is to compare clinical aspects of and , a species of that is known to be bacteriologically similar to spp.
METHODS
Using data collected at a tertiary care hospital in the United States, we identified 43 patients with infection and 1173 patients with infection. We compared patient demographics (age and sex), hospitalization status, isolation sites and antibiotic resistance profiles between the two species.
RESULTS
There was no significant difference in patient demographics between the two bacteria species. The proportions of intensive care unit (ICU) admission were higher among patients with infection (p=0.008). The most common site of isolation was urine for both species (39.5% of all patients with spp. vs. 59.3% for ). The second most common site of isolation was blood stream for spp. (23.3%) and respiratory tract for (10.8%). Except for the high proportion of resistant isolates of spp. for Trimethoprim/sulfamethoxazole, the antibiotic susceptibility profiles were similar between the two bacteria species. Both were susceptible to ciprofloxacin and meropenem.
CONCLUSION
While there are no significant differences in the patient demographics and antibiotic susceptibility profiles between spp. and , may cause more serious infection requiring ICU admissions. Also, may cause blood stream infection more frequently than .
Topics: Humans; Male; Klebsiella oxytoca; Female; Middle Aged; Aged; Enterobacteriaceae; Klebsiella Infections; Anti-Bacterial Agents; Enterobacteriaceae Infections; Microbial Sensitivity Tests; Adult; Tertiary Care Centers; Intensive Care Units; United States; Aged, 80 and over; Drug Resistance, Bacterial
PubMed: 38887491
DOI: 10.3389/fcimb.2024.1260212 -
Cureus May 2024Introduction Antimicrobial resistance poses a significant global healthcare challenge in the management of bacterial infections, which is frequently attributed to rapid...
Introduction Antimicrobial resistance poses a significant global healthcare challenge in the management of bacterial infections, which is frequently attributed to rapid bacterial adaptations. This study aims to develop an antibiogram for a tertiary care hospital, providing comprehensive antibiotic sensitivity profiles for Gram-positive and Gram-negative bacteria. It informs healthcare providers of antibiotic resistance trends, enabling informed treatment decisions and enhanced infection control measures. Methods We conducted a six-month prospective observational study, during which we gathered and analyzed data from the microbiology laboratory to identify patterns of antimicrobial sensitivity. Subsequently, the data underwent analysis and interpretation using the respected WHONET software, a readily available tool designed for this specific task. Our methodology adhered to the guidelines established by the Clinical & Laboratory Standards Institute for the standardization of antibiogram generation procedures, and these guidelines are easily integrated into the WHONET software for analytical purposes. Results There were a total of 357 isolates across various hospital departments, comprising 13 distinct bacterial species. Among them, nine were identified as Gram-negative bacteria, accounting for 262 (73.3%) isolates. accounted for 131 (36.6%) isolates, while accounted for 62 (17.3%), emerging as the predominant species among them. The remaining four bacterial species were identified as Gram-positive bacteria, totaling 95 (26.6%) isolates, with being the most frequently isolated species at 51 (14.2%), followed by at 26 (7.2%). Subsequent analysis using the WHONET software facilitated the creation of an antibiogram. Among the Gram-negative bacteria, displayed high sensitivity (100%) to aztreonam and clindamycin, followed by nitrofurantoin (98%), imipenem (94%), and meropenem (95%). However, it exhibited decreased sensitivity to ampicillin (25%), cefuroxime (34%), and ceftriaxone (39%). Conversely, among the Gram-positive bacteria, demonstrated 100% sensitivity to ampicillin, amoxiclav, cefazolin, teicoplanin, linezolid, rifampicin, nitrofurantoin, and cefotaxime. However, it exhibited zero sensitivity to vancomycin and only 6% sensitivity to cotrimoxazole. Conclusion This study advances the understanding of antibiotic susceptibility in a tertiary care setting and provides an invaluable tool for optimizing treatment strategies, enhancing infection control measures, and combating antibiotic resistance.
PubMed: 38887355
DOI: 10.7759/cureus.60542 -
Annals of Clinical Microbiology and... Jun 2024Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat...
BACKGROUND
Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat pathogens due to both intrinsic resistance and the possibility of acquired antimicrobial resistance. Species identification remains challenging leading to imprecise descriptions of resistance in each taxon. Cefiderocol is a broad-spectrum siderophore cephalosporin increasingly used in the management of Achromobacter infections for which susceptibility data remain scarce. We aimed to describe the susceptibility to cefiderocol of a collection of Achromobacter strains encompassing different species and isolation sources from CF or non-CF (NCF) patients.
METHODS
We studied 230 Achromobacter strains (67 from CF, 163 from NCF patients) identified by nrdA gene-based analysis, with available susceptibility data for piperacillin-tazobactam, meropenem and trimethoprim-sulfamethoxazole. Minimal inhibitory concentrations (MICs) of cefiderocol were determined using the broth microdilution reference method according to EUCAST guidelines.
RESULTS
Strains belonged to 15 species. A. xylosoxidans represented the main species (71.3%). MICs ranged from ≤ 0.015 to 16 mg/L with MIC of ≤ 0.015/0.5 mg/L overall and 0.125/2 mg/L against 27 (11.7%) meropenem-non-susceptible strains. Cefiderocol MICs were not related to CF/NCF origin or species although A. xylosoxidans MICs were statistically lower than those of other species considered as a whole. Considering the EUCAST non-species related breakpoint (2 mg/L), 228 strains (99.1%) were susceptible to cefiderocol. The two cefiderocol-resistant strains (A. xylosoxidans from CF patients) represented 3.7% of meropenem-non-susceptible strains and 12.5% of MDR strains.
CONCLUSIONS
Cefiderocol exhibited excellent in vitro activity against a large collection of accurately identified Achromobacter strains, irrespective of species and origin.
Topics: Microbial Sensitivity Tests; Humans; Achromobacter; Anti-Bacterial Agents; Cephalosporins; Cefiderocol; Cystic Fibrosis; Gram-Negative Bacterial Infections
PubMed: 38886694
DOI: 10.1186/s12941-024-00709-z