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Journal of Infection in Developing... Feb 2022Dynamic movement in the hospital environment promotes the transmission of nosocomial pathogens and multidrug resistance mechanisms through the dissemination of organisms...
INTRODUCTION
Dynamic movement in the hospital environment promotes the transmission of nosocomial pathogens and multidrug resistance mechanisms through the dissemination of organisms that carry genetic determinants. Healthcare workers play an important role in the spread of pathogens; however, the role of visitors in this environment is poorly understood.
OBJECTIVE
This study aimed to molecularly identify and examine the antibiotic resistance of the palmar microbiota of patients' companions in a hospital waiting room.
METHODOLOGY
Twenty-five palmar surface and interdigital space sample swabs were randomly collected and cultured on blood agar plates, and 19 colonies with different macro- and microscopic characteristics were isolated. The V4 and V6 hypervariable regions of the 16S rRNA gene from each isolate were amplified by PCR and sequenced. Maximum likelihood- and Bayesian inference-based phylogenetic analyses were performed to determine taxonomic relationships. Antibiotic resistance was evaluated by disk diffusion and broth microdilution.
RESULTS
Among the isolates, 52.6% were related to Bacillus, 36.8% to Staphylococcus, 5.3% to Enterococcus and 5.3% to Atlantibacter. All of the isolates exhibited ampicillin and penicillin resistance, while 94.7% also exhibited dicloxacillin resistance. Staphylococcus aureus was resistant to penicillins but sensitive to the remaining drugs. Bacteria identified as Bacillus subtilis (MLM14B99), Bacillus pumilus (MLM23B07 and MLM25B06), Staphylococcus epidermidis (MLM24S31 and MLM29S04), and Enterococcus (MLM22E08) showed resistance to at least 46.7% of the antibiotics.
CONCLUSIONS
To decrease the transmission of pathogenic bacteria with an antibiotic resistance profile, re-evaluation of hand cleaning measures and their application by people who visit hospital centres is needed.
Topics: Bayes Theorem; Drug Resistance, Microbial; Hospitals; Humans; Phylogeny; RNA, Ribosomal, 16S; Staphylococcus epidermidis
PubMed: 35298428
DOI: 10.3855/jidc.15252 -
British Journal of Clinical Pharmacology Mar 2018The most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. Despite using prophylactic antibiotics, infections are still seen.... (Clinical Trial)
Clinical Trial
AIMS
The most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men.
METHODS
MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analysed with high performance liquid chromatography (HPLC).
RESULTS
The maximum concentration was reached in muscle tissue after 0.5 h and in adipose tissue after 0.8 h. AUC for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 h and a median of 4.1 h in muscle tissue and a minimum of 1.8 h and a median of 3.2 h in adipose tissue.
CONCLUSIONS
The unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopaedic procedures. Whether this is true in patients with compromised circulation remains to be investigated.
Topics: Adipose Tissue; Administration, Intravenous; Adult; Anti-Bacterial Agents; Area Under Curve; Chromatography, High Pressure Liquid; Dicloxacillin; Humans; Male; Microbial Sensitivity Tests; Microdialysis; Muscle, Skeletal; Staphylococcus aureus; Tissue Distribution
PubMed: 29105799
DOI: 10.1111/bcp.13468 -
Antibiotics (Basel, Switzerland) Dec 2021Gram-negative Tripartite Resistance Nodulation and cell Division (RND) superfamily efflux pumps confer various functions, including multidrug and bile salt resistance,...
Gram-negative Tripartite Resistance Nodulation and cell Division (RND) superfamily efflux pumps confer various functions, including multidrug and bile salt resistance, quorum-sensing, virulence and can influence the rate of mutations on the chromosome. Multidrug RND efflux systems are often characterized by a wide substrate specificity. Similarly to many other RND efflux pump systems, AcrAD-TolC confers resistance toward SDS, novobiocin and deoxycholate. In contrast to the other pumps, however, it in addition confers resistance against aminoglycosides and dianionic β-lactams, such as sulbenicillin, aztreonam and carbenicillin. Here, we could show that AcrD from confers resistance toward several hitherto unreported AcrD substrates such as temocillin, dicloxacillin, cefazolin and fusidic acid. In order to address the molecular determinants of the AcrD substrate specificity, we conducted substitution analyses in the putative access and deep binding pockets and in the TM1/TM2 groove region. The variants were tested in ΔΔ against β-lactams oxacillin, carbenicillin, aztreonam and temocillin. Deep binding pocket variants N136A, D276A and Y327A; access pocket variant R625A; and variants with substitutions in the groove region between TM1 and TM2 conferred a sensitive phenotype and might, therefore, be involved in anionic β-lactam export. In contrast, lower susceptibilities were observed for cells harbouring deep binding pocket variants T139A, D176A, S180A, F609A, T611A and F627A and the TM1/TM2 groove variant I337A. This study provides the first insights of side chains involved in drug binding and transport for AcrD from .
PubMed: 34943706
DOI: 10.3390/antibiotics10121494 -
Antimicrobial Agents and Chemotherapy Apr 2011The small-colony-variant (SCV) phenotype of Staphylococcus aureus has been associated with difficult-to-treat infections, reduced antimicrobial susceptibility, and...
Intra- and extracellular activities of dicloxacillin and linezolid against a clinical Staphylococcus aureus strain with a small-colony-variant phenotype in an in vitro model of THP-1 macrophages and an in vivo mouse peritonitis model.
The small-colony-variant (SCV) phenotype of Staphylococcus aureus has been associated with difficult-to-treat infections, reduced antimicrobial susceptibility, and intracellular persistence. This study represents a detailed intra- and extracellular investigation of a clinical wild-type (WT) S. aureus strain and its counterpart with an SCV phenotype both in vitro and in vivo, using the THP-1 cell line model and the mouse peritonitis model, respectively. Bacteria of both phenotypes infected the mouse peritoneum intra- and extracellularly. The SCV phenotype was less virulent and showed distinct bacterial clearance, a reduced multiplication capacity, and a reduced internalization ability. However, some of the SCV-infected mice were still culture positive up to 96 h postinfection, and bacteria of this phenotype could spread to the mouse kidney and furthermore revert to the more virulent WT phenotype in both the mouse peritoneum and kidney. The SCV phenotype is therefore, despite reduced virulence, an important player in S. aureus pathogenesis. In the THP-1 cell line model, both dicloxacillin (DCX) and linezolid (LZD) reduced the intracellular inocula of bacteria of both phenotypes by approximately 1 to 1.5 log(10) in vitro, while DCX was considerably more effective against extracellular bacteria. In the mouse peritonitis model, DCX and LZD were also able to control both intra- and extracellular infections caused by either phenotype. Treatment with a single dose of DCX and LZD was, however, insufficient to clear the SCVs in the kidneys, and the risk of recurrent infection remained. This stresses the importance of an optimal dosing of the antibiotic when SCVs are present.
Topics: Acetamides; Animals; Anti-Bacterial Agents; Dicloxacillin; Doublecortin Protein; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Linezolid; Macrophages; Mice; Oxazolidinones; Peritonitis; Phenotype; Staphylococcal Infections; Staphylococcus aureus
PubMed: 21282430
DOI: 10.1128/AAC.00205-10 -
The British Journal of Dermatology Oct 2022Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's...
BACKGROUND
Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear.
OBJECTIVES
To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy.
METHODS
We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables.
RESULTS
A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin].
CONCLUSIONS
Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS.
Topics: Acitretin; Anti-Bacterial Agents; Biological Factors; Biological Products; Clindamycin; Dapsone; Dicloxacillin; Drug Utilization; Hidradenitis Suppurativa; Humans; Isotretinoin; Rifampin; Tetracyclines
PubMed: 35603888
DOI: 10.1111/bjd.21673 -
Journal of Orthopaedic Research :... Apr 2018Staphylococcus aureus is often found in orthopaedic infections and may be protected from commonly prescribed antibiotics by forming biofilms or growing intracellularly...
Staphylococcus aureus is often found in orthopaedic infections and may be protected from commonly prescribed antibiotics by forming biofilms or growing intracellularly within osteoblasts. To investigate the effect of non-antibiotic compounds in conjunction with antibiotics to clear intracellular and biofilm forming S. aureus causing osteomyelitis. SAOS-2 osteoblast-like cell lines were infected with S. aureus BB1279. Antibiotics (vancomycin, VAN; and dicloxacillin, DICLOX), bacterial efflux pump inhibitors (piperine, PIP; carbonyl cyanide m-chlorophenyl hydrazone, CCCP), and bone morphogenetic protein (BMP-2) were evaluated individually and in combination to kill intracellular bacteria. We present direct evidence that after gentamicin killed extracellular planktonic bacteria and antibiotics had been stopped, seeding from the infected osteoblasts grew as biofilms. VAN was ineffective in treating the intracellular bacteria even at 10× MIC; however in presence of PIP or CCCP the intracellular S. aureus was significantly reduced. Bacterial efflux pump inhibitors (PIP and CCCP) were effective in enhancing permeability of antibiotics within the osteoblasts and facilitated killing of intracellular S. aureus. Confocal laser scanning microscopy (CLSM) showed increased uptake of propidium iodide within osteoblasts in presence of PIP and CCCP. BMP-2 had no effect on growth of S. aureus either alone or in combination with antibiotics. Combined application of antibiotics and natural agents could help in the treatment of osteoblast infected intracellular bacteria and biofilms associated with osteomyelitis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1086-1092, 2018.
Topics: Alkaloids; Anti-Bacterial Agents; Benzodioxoles; Bone Morphogenetic Protein 2; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Cell Line, Tumor; Dicloxacillin; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Host-Pathogen Interactions; Humans; Microbial Sensitivity Tests; Osteoblasts; Osteomyelitis; Piperidines; Polyunsaturated Alkamides; Staphylococcal Infections; Staphylococcus aureus; Vancomycin
PubMed: 28885721
DOI: 10.1002/jor.23723 -
Antimicrobial Agents and Chemotherapy Jun 2010Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response and recurrences. The intracellular persistence of the...
Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response and recurrences. The intracellular persistence of the staphylococci offers a plausible explanation for the treatment difficulties because of the impaired intracellular efficacies of the antibiotics. The intra- and extracellular time- and concentration-kill relationships were examined in vitro with THP-1 cells and in vivo by use of a mouse peritonitis model. The in vivo model was further used to estimate the most predictive pharmacokinetic/pharmacodynamic (PK/PD) indices (the ratio of the maximum concentration of drug in plasma/MIC, the ratio of the area under the concentration-time curve/MIC, or the cumulative percentage of a 24-h period that the free [f] drug concentration exceeded the MIC under steady-state pharmacokinetic conditions [fT(MIC)]) for dicloxacillin (DCX) intra- and extracellularly. In general, DCX was found to have similar intracellular activities, regardless of the model used. Both models showed (i) the relative maximal efficacy (1-log-unit reduction in the numbers of CFU) of DCX intracellularly and (ii) the equal relative potency of DCX intra- and extracellularly, with the MIC being a good indicator of the overall response in both situations. Discordant results, based on data obtained different times after dosing, were obtained from the two models when the extracellular activity of DCX was measured, in which the in vitro model showed a considerable reduction in the number of CFU from that in the original inoculum (3-log-unit decrease in the number of CFU after 24 h), whereas the extracellular CFU reduction achieved in vivo after 4 h did not exceed 1 log unit. Multiple dosing of DCX in vivo revealed increased extra- and intracellular efficacies (2.5 log and 2 log units of reduction in the numbers of CFU after 24 h, respectively), confirming that DCX is a highly active antistaphylococcal antibiotic. PK/PD analysis revealed that fT(MIC) is the index that is the most predictive of the outcome of infection both intra- and extracellularly.
Topics: Animals; Anti-Bacterial Agents; Cell Line; Colony Count, Microbial; Dicloxacillin; Doublecortin Protein; Extracellular Space; Female; Humans; In Vitro Techniques; Intracellular Space; Macrophages; Mice; Microbial Sensitivity Tests; Peritonitis; Staphylococcal Infections; Staphylococcus aureus
PubMed: 20308386
DOI: 10.1128/AAC.01400-09 -
Acta Orthopaedica Dec 2016Background and purpose - Acute kidney injury is a known complication of antibiotic use. Antibiotic prophylaxis is essential to prevent periprosthetic infections after...
Background and purpose - Acute kidney injury is a known complication of antibiotic use. Antibiotic prophylaxis is essential to prevent periprosthetic infections after total hip replacement. We experienced a rise in the incidence of acute kidney injury (AKI), and in an effort to solve this problem, we changed our antibiotic prophylaxis protocol. We investigated whether removing gentamicin from our antibiotic protocol would cause fewer and less severe cases of renal impairment. Patients and methods - We performed a retrospective study involving 136 cases of total hip replacement, with 66 patients receiving dicloxacillin and gentamicin and 70 patients receiving dicloxacillin alone. Results - We found less cases of AKI in the dicloxacillin group (p = 0.03): the mean creatine level in the dicloxacillin/gentamicin group was 126 (25-422) μmol/L whereas it was 93 (39-278) μmol/L in the group that received dicloxacillin alone. We also found that cases were less severe in the dicloxacillin group than in the dicloxacillin/gentamicin group (p = 0.02). The relative risk of developing AKI was 3 times higher if dicloxacillin and gentamicin were both used (p = 0.02). Interpretation - After removing gentamicin, there were fewer and less severe cases of acute kidney injury.
Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Arthroplasty, Replacement, Hip; Denmark; Dicloxacillin; Female; Gentamicins; Humans; Incidence; Male; Middle Aged; Prognosis; Retrospective Studies; Surgical Wound Infection
PubMed: 27648882
DOI: 10.1080/17453674.2016.1231008 -
Microorganisms Dec 2021Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This...
Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This study aimed to investigate how broad- and narrow-spectrum antibiotics affect the gut microbiome and the resistome in antibiotic naïve patients during neurointensive care. Patients admitted to the neurointensive care unit were treated with broad-spectrum (meropenem or piperacillin/tazobactam) or narrow-spectrum antibiotic treatment (including ciprofloxacin, cefuroxime, vancomycin and dicloxacillin) according to clinical indications. A rectal swab was collected from each patient before and after 5-7 days of antibiotic therapy ( = 34), respectively. Shotgun metagenomic sequencing was performed and the composition of metagenomic species (MGS) was determined. The resistome was characterized with CARD RGI software and the CARD database. As a measure for selection pressure in the patient, we used the sum of the number of days with each antibiotic (antibiotic days). We observed a significant increase in richness and a tendency for an increase in the Shannon index after narrow-spectrum treatment. For broad-spectrum treatment the effect was more diverse, with some patients increasing and some decreasing in richness and Shannon index. This was studied further by comparison of patients who had gained or lost >10 MGS, respectively. Selection pressure was significantly higher in patients with decreased richness and a decreased Shannon index who received the broad treatment. A decrease in MGS richness was significantly correlated to the number of drugs administered and the selection pressure in the patient. Bray-Curtis dissimilarities were significant between the pre- and post-treatment of samples in the narrow group, indicating that the longer the narrow-spectrum treatment, the higher the differences between the pre- and the post-treatment microbial composition. We did not find significant differences between pre- and post-treatment for both antibiotic spectrum treatments; however, we observed that most of the antibiotic class resistance genes were higher in abundance in post-treatment after broad-spectrum treatment.
PubMed: 34946144
DOI: 10.3390/microorganisms9122542 -
The Journal of Antibiotics Jul 1980The membrane fraction prepared from beta-lactamase producing Citrobacter freundii GN346 catalyzed in vitro peptidoglycan synthesis from...
Effect of a combination of benzylpenicillin or ampicillin and dicloxacillin on peptidoglycan synthesis in a cell-free enzyme system from a beta-lactamase producing strain of Citrobacter freundii.
The membrane fraction prepared from beta-lactamase producing Citrobacter freundii GN346 catalyzed in vitro peptidoglycan synthesis from uridine-5'-diphosphate-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelyl- D-alanyl-D-alanine and uridine-5'-diphosphate-N-acetylglucosamine, which was accompanied by the release of alanine from the carboxyl terminal end of the former substrate. Though this reaction was inhibited by benzylpenicillin (PCG) and ampicillin (ABPC), the reaction was relatively insensitive compared with that catalyzed by the membrane fraction from a derived beta-lactamaseless mutant strain GN346/16. In contrast, the enzyme activity of the parent strain was strongly inhibited by a combination of PCG or ABPC and dicloxacillin (MDIPC). The beta-lactamase present in the membrane fraction from the parent strain showed stronger activity than that from the mutant strain, and the activity was inhibited by MDIPC as in the case of the soluble enzyme localized in the periplasmic space.
Topics: Ampicillin; Cell-Free System; Citrobacter; Dicloxacillin; Drug Interactions; Penicillin G; Peptidoglycan; beta-Lactamases
PubMed: 6967868
DOI: 10.7164/antibiotics.33.731