scholarly journals Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

2010 ◽  
Vol 23 (1) ◽  
pp. 99-139 ◽  
Author(s):  
Benjamin P. Howden ◽  
John K. Davies ◽  
Paul D. R. Johnson ◽  
Timothy P. Stinear ◽  
M. Lindsay Grayson
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Treatment Failure ◽  
Treatment Outcomes ◽  
Susceptibility Testing ◽  
Point Mutations ◽  
Resistance Mechanisms ◽  
Wall Thickening ◽  
Clinical Implications ◽  
The Past

SUMMARY The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus, it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus.

scholarly journals Recent Insights into Antibiotic Resistance inHelicobacter pyloriEradication

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wenming Wu ◽  
Yunsheng Yang ◽  
Gang Sun
Keyword(s):  
Antibiotic Resistance ◽  
Treatment Failure ◽  
Point Mutations ◽  
Resistance Mechanisms ◽  
Current Status ◽  
Quadruple Therapy ◽  
The Past ◽  
Highly Active ◽  
Alternative Approaches ◽  
H Pylori

Antibiotics have been useful in the treatment ofH. pylori-related benign and malignant gastroduodenal diseases. However, emergence of antibiotic resistance often decreases the eradication rates ofH. pyloriinfections. Many factors have been implicated as causes of treatment failure, but the main antibiotic resistance mechanisms described to date are due to point mutations on the bacterial chromosome, a consequence of a significantly phenotypic variation inH. pylori. The prevalence of antibiotic (e.g., clarithromycin, metronidazole, tetracycline, amoxicillin, and furazolidone) resistance varies among different countries; it appears to be partly determined by geographical factors. Since the worldwide increase in the rate of antibiotic resistance represents a problem of relevance, some studies have been performed in order to identify highly active and well-tolerated anti-H. pyloritherapies including sequential, concomitant quadruple, hybrid, and quadruple therapy. These represent a promising alternatives in the effort to overcome the problem of resistance. The aim of this paper is to review the current status of antibiotic resistance inH. pylorieradication, highlighting the evolutionary processes in detail at alternative approaches to treatment in the past decade. The underlying resistance mechanisms will be also followed.

scholarly journals Summary of Linezolid Activity and Resistance Mechanisms Detected during the 2012 LEADER Surveillance Program for the United States

2013 ◽  
Vol 58 (2) ◽  
pp. 1243-1247 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
Patricia A. Hogan ◽  
James E. Ross ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Susceptibility Testing ◽  
The United States ◽  
Resistance Mechanisms ◽  
Regulatory Approval ◽  
Surveillance Program ◽  
Gram Positive ◽  
Content Type

ABSTRACTThis study summarizes the linezolid susceptibility testing results for 7,429 Gram-positive pathogens from 60 U.S. sites collected during the 2012 sampling year for the LEADER Program. Linezolid showed potent activity when tested against 2,980Staphylococcus aureusisolates, inhibiting all but 3 at ≤2 μg/ml. Similarly, linezolid showed coverage against 99.5% of enterococci, as well as for all streptococci tested. These results confirm a long record of linezolid activity against U.S. Gram-positive isolates since regulatory approval in 2000.

scholarly journals Setting up a methadone maintenance clinic in a hostel in London's West End

2006 ◽  
Vol 30 (9) ◽  
pp. 337-339
Author(s):  
John Dunn ◽  
David Robertson ◽  
Paul Davis ◽  
Babak Khosrawan ◽  
Suneel Christian
Keyword(s):  
Treatment Outcomes ◽  
Substance Misuse ◽  
Methadone Maintenance ◽  
Homeless People ◽  
Clinical Implications ◽  
Original Cohort ◽  
Heroin Use ◽  
The Past ◽  
Outreach Clinic ◽  
Set Up

Aims and MethodA satellite methadone prescribing service was set up in a hostel in London's West End. The aim was to investigate if it were feasible to engage and retain these hard-to-reach, chaotic, polydrug users in treatment. A basic needs assessment was undertaken with staff and clients at the hostel. Treatment outcomes were assessed at 16 weeks using the Maudsley Addiction Profile.ResultsAt 16 weeks 87% of the original cohort (26 out of 30) were still in treatment. There were also significant reductions in mean heroin use (from 29.7 to 14.5 out of the past 30 days, P<0.001) and in the frequency of injecting (from 25.9 to 15.9 days, P<0.001).Clinical ImplicationsThis outreach clinic offers a model for developing services to homeless people with substance misuse problems.

scholarly journals 1603. Observation of Treatment Outcomes During an Outbreak of Multidrug-Resistant Shigella sonnei Infections in a Retirement Community—Vermont, 2018

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S584-S585
Author(s):  
Radhika Gharpure ◽  
Louise Francois Watkins ◽  
Louise Francois Watkins ◽  
Veronica Fialkowski ◽  
Jennifer P Collins ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Treatment Outcomes ◽  
Clinical Decision Making ◽  
Susceptibility Testing ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Shigella Sonnei ◽  
Retirement Community ◽  
Severe Illness ◽  
Clinical Failure

Abstract Background In 2018, CDC and the Vermont Department of Health investigated an outbreak of multidrug-resistant Shigella sonnei infections in a retirement community. Most Shigella infections are self-limited, but antibiotics are indicated for severe illness and sometimes to limit transmission. The Clinical and Laboratory Standards Institute has not yet established breakpoints for azithromycin, so laboratories cannot report resistance. Although breakpoints exist for ciprofloxacin, isolates with one fluoroquinolone resistance mechanism typically have minimum inhibitory concentrations within the susceptible range (≤ 0.25 µg/mL). Methods We reviewed charts for treatment outcomes of outbreak patients to evaluate clinical and microbiologic response. We defined clinical failure as ≥ 3 loose stools per day for ≥ 1 day after completion of antibiotics and microbiologic failure as a positive stool culture after completion of antibiotics. We used broth microdilution to perform antimicrobial susceptibility testing, and whole-genome sequencing to identify resistance mechanisms. Results Among the 24 patients with culture-confirmed Shigella infection, 4 were hospitalized and 2 died. All isolates were multidrug-resistant (Table 1) and harbored mechanisms for resistance to ampicillin, ceftriaxone, trimethoprim-sulfamethoxazole, azithromycin, and ciprofloxacin. Fifteen patients received one course of ciprofloxacin, 5 received multiple courses of antibiotics, and 4 received no antibiotics. Overall, 6 patients had treatment failure (Table 2); all 4 patients who received azithromycin had subsequent clinical failure and 2 also had microbiologic failure. Two patients had failure after ciprofloxacin (1 clinical, 1 microbiologic). Conclusion This outbreak of highly resistant shigellosis highlights the importance of comprehensive susceptibility testing and systematic outcome studies. Evidence of treatment failure after azithromycin suggests that an appropriate clinical breakpoint is needed to inform clinical decision-making. Ciprofloxacin treatment failures were observed in patients with a susceptible strain harboring a resistance mechanism, warranting further investigation. Disclosures All authors: No reported disclosures.

scholarly journals Altering the Proclivity towards Daptomycin Resistance in Methicillin-Resistant Staphylococcus aureus Using Combinations with Other Antibiotics

2012 ◽  
Vol 56 (10) ◽  
pp. 5046-5053 ◽  
Author(s):  
Andrew D. Berti ◽  
Justine E. Wergin ◽  
Gary G. Girdaukas ◽  
Scott J. Hetzel ◽  
George Sakoulas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Membrane ◽  
Membrane Integrity ◽  
Wall Thickening ◽  
Methicillin Resistant ◽  
Content Type ◽  
Cell Membrane Integrity ◽  
Cell Membrane Fluidity

ABSTRACTDaptomycin (DAP) is increasingly used as a part of combination therapy, particularly in complex methicillin-resistantStaphylococcus aureus(MRSA) infections. While multiple studies have reported the potential for synergy between DAP and adjunctive anti-infectives, few have examined the influence of adjunctive therapy on the emergence of DAP resistance. This study examined eight adjunctive antimicrobial combinations with DAPin vitroand the emergence of DAP resistance over time (up to 4 weeks) using clinical isolates of DAP-susceptible MRSA (MIC, 0.5 μg/ml) in which DAP resistance subsequently developed during patient therapy (MIC, 3 μg/ml). In addition to DAP susceptibility testing, selected strains were examined for phenotypic changes associated with DAP resistance, including changes to cell wall thickness (CWT) and cell membrane alterations. The addition of either oxacillin or clarithromycin in medium containing DAP significantly inhibited the development of DAP resistance through the entirety of the 4-week exposure (10- to 32-fold MIC reduction from that of DAP alone). Combinations with rifampin or fosfomycin were effective in delaying the emergence of DAP resistance through the end of week one only (week one MIC, 0.5 μg/ml; week four MIC, 24 μg/ml). Cell wall thickening was observed for all antibiotic combinations regardless of their effect on the DAP MIC (14 to 70% increase in CWT), while changes in cell membrane fluidity were variable and treatment dependent. DAP showed reduced activity against strains with DAP MICs of 1 to 12 μg/ml, but cell membrane integrity was still disrupted at concentrations achieved with doses greater than 10 mg/kg of body weight. The emergence of DAP resistance in MRSA is strongly influenced by the presence of subinhibitory concentrations of adjunctive antimicrobials. These data suggest that combining DAP with oxacillin or clarithromycin may delay the development of DAP resistance in cases requiring prolonged antibiotic therapy.

scholarly journals Correlation between resistance mechanisms in Staphylococcus aureus and cell wall and septum thickening

2017 ◽  
Vol Volume 10 ◽  
pp. 353-356 ◽  
Author(s):  
Ana Belén García ◽  
José Manuel Viñuela Prieto ◽  
Laura Lopez González ◽  
Francisco Javier Candel
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Resistance Mechanisms

scholarly journals Complete Reconstitution of the Vancomycin-Intermediate Staphylococcus aureus Phenotype of Strain Mu50 in Vancomycin-Susceptible S. aureus

2016 ◽  
Vol 60 (6) ◽  
pp. 3730-3742 ◽  
Author(s):  
Yuki Katayama ◽  
Miwa Sekine ◽  
Tomomi Hishinuma ◽  
Yoshifumi Aiba ◽  
Keiichi Hiramatsu
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Mutant Strain ◽  
Vancomycin Resistance ◽  
Wall Thickening ◽  
Cell Physiology ◽  
Content Type ◽  
Sequence Deletion ◽  
Quadruple Mutant ◽  
Genetic Events

Complete reconstitution of the vancomycin-intermediateStaphylococcus aureus(VISA) phenotype of strain Mu50 was achieved by sequentially introducing mutations into six genes of vancomycin-susceptibleS. aureus(VSSA) strain N315ΔIP. The six mutated genes were detected in VISA strain Mu50 but not in N315ΔIP. Introduction of the mutation Ser329Leu intovraS, encoding the sensor histidine kinase of thevraSRtwo-component regulatory (TCR) system, and another mutation, Glu146Lys, intomsrR, belonging to the LytR-CpsA-Psr (LCP) family, increased the level of vancomycin resistance to that detected in heterogeneous vancomycin-intermediateS. aureus(hVISA) strain Mu3. Introduction of two more mutations, Asn197Ser intograRof thegraSRTCR system and His481Tyr intorpoB, encoding the β subunit of RNA polymerase, converted the hVISA strain into a VISA strain with the same level of vancomycin resistance as Mu50. Surprisingly, however, the constructed quadruple mutant strain ΔIP4 did not have a thickened cell wall, a cardinal feature of the VISA phenotype. Subsequent study showed that cell wall thickening was an inducible phenotype in the mutant strain, whereas it was a constitutive one in Mu50. Finally, introduction of the Ala297Val mutation intofdh2, which encodes a putative formate dehydrogenase, or a 67-amino-acid sequence deletion intosle1[sle1(Δ67aa)], encoding the hydrolase ofN-acetylmuramyl-l-alanine amidase in the peptidoglycan, converted inducible cell wall thickening into constitutive cell wall thickening.sle1(Δ67aa) was found to cause a drastic decrease in autolysis activity. Thus, all six mutated genes required for acquisition of the VISA phenotype were directly or indirectly involved in the regulation of cell physiology. The VISA phenotype seemed to be achieved through multiple genetic events accompanying drastic changes in cell physiology.

scholarly journals Predictors of Adverse Outcomes in Children With Staphylococcus aureus Bacteremia

2017 ◽  
Vol 22 (3) ◽  
pp. 218-226
Author(s):  
Ganesh Kumarachandran ◽  
Jennifer Kristie Johnson ◽  
Debbie-Ann Shirley ◽  
Eileen Graffunder ◽  
Emily L. Heil
Keyword(s):  
Staphylococcus Aureus ◽  
Minimum Inhibitory Concentration ◽  
High Risk ◽  
Treatment Failure ◽  
Treatment Outcomes ◽  
Inhibitory Concentration ◽  
Factors Associated ◽  
Staphylococcus Aureus Bacteremia ◽  
Vancomycin Minimum Inhibitory Concentration ◽  
Risk Source

OBJECTIVES Staphylococcus aureus bacteremia is a common infection, associated with significant morbidity and mortality in children. Factors associated with adverse treatment outcomes are poorly understood in the pediatric population. METHODS Our study compared clinical and microbiologic characteristics of children admitted during a 5-year period (2007–2012) to a large university-based hospital and found to have S aureus bacteremia with outcome measures, in order to identify risk factors associated with treatment failure (defined as 30-day mortality, delayed microbiologic resolution, or recurrence of S aureus bacteremia within 60 days of completing effective antibiotic therapy). RESULTS In all, 71 patients were found to have S aureus bacteremia, and of these, 17 patients (24%) experienced treatment failure. Based on the logistic regression model, only high vancomycin minimum inhibitory concentration in combination with a high-risk source of infection (i.e., infected graft or device, intra-abdominal infection, or respiratory tract infection) was significantly associated with risk of treatment failure. CONCLUSIONS Infection associated with a high-risk source may increase the chance of treatment failure in pediatric patients with S aureus bacteremia. Vancomycin minimum inhibitory concentration alone was not found to be a predictor of treatment outcomes.

scholarly journals Is Early Monitoring Better? Impact of Early Vancomycin Exposure on Treatment Outcomes and Nephrotoxicity in Patients with Methicillin-Resistant Staphylococcus aureus Infections

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 672 ◽  
Author(s):  
Thanawat Chattaweelarp ◽  
Dhitiwat Changpradub ◽  
Baralee Punyawudho ◽  
Sudaluck Thunyaharn ◽  
Wichai Santimaleeworagun
Keyword(s):  
Staphylococcus Aureus ◽  
Acute Kidney Injury ◽  
Treatment Failure ◽  
Treatment Outcomes ◽  
Clinical Outcomes ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Kidney Injury ◽  
Methicillin Resistant ◽  
Increased Risk ◽  
Broth Microdilution Method

Optimal early vancomycin target exposure remains controversial. To clarify the therapeutic exposure range, we investigated the association between vancomycin exposure and treatment outcomes or nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. This retrospective study reviewed clinical data obtained from 131 patients with MRSA infections between January 2017 and September 2019. Clinical outcomes included treatment failure, 30-day mortality, microbiological failure, and acute kidney injury. We measured serum vancomycin levels after the first dose to 48 h and estimated vancomycin exposure using the Bayesian theorem. The minimum inhibitory concentration (MIC) of antimicrobial agents was determined using the broth microdilution method. Classification and Regression Tree analyses identified day 1 and 2 exposure thresholds associated with an increased risk of failure and nephrotoxicity. Treatment failure (27.9% vs. 33.3%) and 30-day mortality (26.6% vs. 31.74%) were numerically but not significantly reduced in patients with the area under the curve (AUC)24–48h/MICBMD ≥ 698. Patients with AUCss/MICBMD ≥ 679 exhibited a significantly increased risk of acute kidney injury (27.9% vs. 10.9%, p = 0.041). These findings indicate that AUCss/MICBMD ratios > 600 may cause nephrotoxicity. AUC/MICBMD at days 1 and 2 do not appear to be significantly associated with particular clinical outcomes, but further studies are needed.

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