scholarly journals Trends in Antibiotic Resistance in Coagulase-Negative Staphylococci in the United States, 1999 to 2012

2013 ◽  
Vol 58 (3) ◽  
pp. 1404-1409 ◽  
Author(s):  
Larissa May ◽  
Eili Y. Klein ◽  
Richard E. Rothman ◽  
Ramanan Laxminarayan

ABSTRACTCoagulase-negative staphylococci (CoNS) are important bloodstream pathogens that are typically resistant to multiple antibiotics. Despite the concern about increasing resistance, there have been no recent studies describing the national prevalence of CoNS pathogens. We used national resistance data over a period of 13 years (1999 to 2012) from The Surveillance Network (TSN) to determine the prevalence of and assess the trends in resistance forStaphylococcus epidermidis, the most common CoNS pathogen, and all other CoNS pathogens. Over the course of the study period,S. epidermidisresistance to ciprofloxacin and clindamycin increased steadily from 58.3% to 68.4% and from 43.4% to 48.5%, respectively. Resistance to levofloxacin increased rapidly from 57.1% in 1999 to a high of 78.6% in 2005, followed by a decrease to 68.1% in 2012. Multidrug resistance for CoNS followed a similar pattern, and this rise and small decline in resistance were found to be strongly correlated with levofloxacin prescribing patterns. The resistance patterns were similar for the aggregate of CoNS pathogens. The results from our study demonstrate that the antibiotic resistance in CoNS pathogens has increased significantly over the past 13 years. These results are important, as CoNS can serve as sentinels for monitoring resistance, and they play a role as reservoirs of resistance genes that can be transmitted to other pathogens. The link between the levofloxacin prescription rate and resistance levels suggests a critical role for reducing the inappropriate use of fluoroquinolones and other broad-spectrum antibiotics in health care settings and in the community to help curb the reservoir of resistance in these colonizing pathogens.

2016 ◽  
Vol 60 (5) ◽  
pp. 2680-2683 ◽  
Author(s):  
Guillermo V. Sanchez ◽  
Ahmed Babiker ◽  
Ronald N. Master ◽  
Tony Luu ◽  
Anisha Mathur ◽  
...  

ABSTRACTA retrospective analysis was performed using The Surveillance Network, USA, to examine the prevalence of antibiotic resistance among urine isolates from U.S. female outpatients in 2012 and assessed trends in antibiotic resistance comparing data from 2003 and 2012. The most common pathogen identified in 2012 (n= 285,325) wasEscherichia coli(64.9% of isolates). In 2012,E. coliresistance to nitrofurantoin was low (<3%) across all age groups.E. coliresistance to ciprofloxacin was high among adults (11.8%) and elderly outpatients (29.1%). When comparing the 2003 and 2012 data from isolates from adults,E. coliresistance to nitrofurantoin changed only slightly (from 0.7% to 0.9%), whereas increases in resistance to ciprofloxacin (3.6% to 11.8%) and trimethoprim-sulfamethoxazole (17.2% to 22.2%) changed substantially. In the United States,E. colihas become increasingly resistant to ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX) in adult female outpatients. Nitrofurantoin retains high levels of antibiotic activity against urinaryE. coli.


2019 ◽  
Author(s):  
Mona Nasaj ◽  
Zahra Saeidi ◽  
Babak Asghari ◽  
Ghodratollah Roshanaei ◽  
Mohammad Arabestani

Abstract Objection : Coagulase-negative staphylococci (CoNS) are considered opportunistic pathogens which capable of producing several toxins, enzymes and also resistance genes. The current study aimed to determine the occurrence of different hemolysins and patterns of antibiotic resistance among CoNS species. Results : The highest frequency of antibiotic resistance was observed against cefoxitin in 49 isolates (53.8%), and the lowest resistance was against novobiocin in 5 isolates (5.5%). None of the isolates were resistant to vancomycin. The prevalence of hla, hla_yidD, hld, and hlb genes were determined as 87.9%, 62.6%, 56%, and 47.3%, respectively. The hla/yidD and hld genes were detected in 69.4% of S. epidermidis and the hla gene in 94.6% of S. haemolyticus ; hlb gene was detected in 53.1% of the S. epidermidis isolates. mecA gene was identified in 50 (55%) of the CoNS isolates. In conclusion, the results of statistical analysis showed that the hld gene had a significant association with resistance to levofloxacin and erythromycin and the hlb with clindamycin resistance. The results of this study showed that there is a significant relationship between hemolysin encoding genes and antibiotic resistance patterns; therefore, detection of virulence factors associated with antibiotic resistance has become a significant issue of concern.


2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Robert K. Flamm ◽  
Leonard R. Duncan ◽  
Kamal A. Hamed ◽  
Jennifer I. Smart ◽  
Rodrigo E. Mendes ◽  
...  

ABSTRACT Ceftobiprole medocaril is an advanced-generation cephalosporin prodrug that has qualified infectious disease product status granted by the US FDA and is currently being evaluated in phase 3 clinical trials in patients with acute bacterial skin and skin structure infections (ABSSSIs) and in patients with Staphylococcus aureus bacteremia. In this study, the activity of ceftobiprole and comparators was evaluated against more than 7,300 clinical isolates collected in the United States from 2016 through 2018 from patients with skin and skin structure infections. The major species/pathogen groups were S. aureus (53%), Enterobacterales (23%), Pseudomonas aeruginosa (7%), beta-hemolytic streptococci (6%), Enterococcus spp. (4%), and coagulase-negative staphylococci (2%). Ceftobiprole was highly active against S. aureus (MIC50/90, 0.5/1 mg/liter; 99.7% susceptible by EUCAST criteria; 42% methicillin-resistant S. aureus [MRSA]). Ceftobiprole also exhibited potent activity against other Gram-positive cocci. The overall susceptibility of Enterobacterales to ceftobiprole was 84.8% (>99.0% susceptible for isolate subsets that exhibited a non-extended-spectrum β-lactamase [ESBL] phenotype). A total of 74.4% of P. aeruginosa, 100% of beta-hemolytic streptococci and coagulase-negative staphylococci, and 99.6% of Enterococcus faecalis isolates were inhibited by ceftobiprole at ≤4 mg/liter. As expected, ceftobiprole was largely inactive against Enterobacterales that contained ESBL genes and Enterococcus faecium. Overall, ceftobiprole was highly active against most clinical isolates from the major Gram-positive and Gram-negative skin and skin structure pathogen groups collected at U.S. medical centers participating in the SENTRY Antimicrobial Surveillance Program during 2016 to 2018. The broad-spectrum activity of ceftobiprole, including potent activity against MRSA, supports its further evaluation for a potential ABSSSI indication.


2015 ◽  
Vol 59 (12) ◽  
pp. 7597-7601 ◽  
Author(s):  
Zhaowei Wu ◽  
Fan Li ◽  
Dongliang Liu ◽  
Huping Xue ◽  
Xin Zhao

ABSTRACTExcision and integration of staphylococcal cassette chromosomemec(SCCmec) are mediated by cassette chromosome recombinases (Ccr), which play a crucial role in the worldwide spread of methicillin resistance in staphylococci. We report a novelccrgene,ccrC2, in the SCCmecof aStaphylococcus aureusisolate, BA01611, which showed 62.6% to 69.4% sequence identities to all publishedccrC1sequences. A further survey found that theccrC2gene was mainly located among coagulase-negative staphylococci (CoNS) and could be found in staphylococcal isolates from China, the United States, France, and Germany. Theccrgene complex harboring theccrC2gene was designated a type 9 complex, and the SCCmecof BA01611 was considered a novel type and was designated type XII (9C2). This novel SCCmecelement in BA01611 was flanked by a pseudo-SCC element (ΨSCCBA01611) carrying a truncatedccrA1gene. Both individual SCC elements and a composite SCC were excised from the chromosome based on detection of extrachromosomal circular intermediates. We advocate inclusion of the ccrC2gene and type 9ccrgene complex during revision of the SCCmectyping method.


2012 ◽  
Vol 56 (6) ◽  
pp. 2933-2940 ◽  
Author(s):  
Robert K. Flamm ◽  
Helio S. Sader ◽  
David J. Farrell ◽  
Ronald N. Jones

ABSTRACTTheAssessingWorldwideAntimicrobialResistanceEvaluation (AWARE) surveillance program is a sentinel resistance monitoring system designed to track the activity of ceftaroline and comparator agents. In the United States, a total of 8,434 isolates were collected during the 2010 surveillance program from 65 medical centers distributed across the nine census regions (5 to 10 medical centers per region). All organisms were isolated from documented infections, including 3,055 (36.2%) bloodstream infections, 2,282 (27.1%) respiratory tract infections, 1,965 (23.3%) acute bacterial skin and skin structure infections, 665 (7.9%) urinary tract infections, and 467 (5.5%) miscellaneous other infection sites. Ceftaroline was the most potent β-lactam agent tested against staphylococci. The MIC90values were 1 μg/ml for methicillin-resistantStaphylococcus aureus(MRSA; 98.4% susceptible) and 0.5 μg/ml for methicillin-resistant coagulase-negative staphylococci (CoNS). Ceftaroline was 16- to 32-fold more potent than ceftriaxone against methicillin-susceptible staphylococcal strains. All staphylococcus isolates (S. aureusand CoNS) were inhibited at ceftaroline MIC values of ≤2 μg/ml. Ceftaroline also displayed potent activity against streptococci (MIC90, 0.015 μg/ml for beta-hemolytic streptococci; MIC90, 0.25 μg/ml for penicillin-resistantStreptococcus pneumoniae). Potent activity was also shown against Gram-negative pathogens (Haemophilus influenzae,Haemophilus parainfluenzae, andMoraxella catarrhalis). Furthermore, wild-type strains ofEnterobacteriaceae(non-extended-spectrum β-lactamase [ESBL]-producing strains and non-AmpC-hyperproducing strains) were often susceptible to ceftaroline. Continued monitoring through surveillance networks will allow for the assessment of the evolution of resistance as this new cephalosporin is used more broadly to provide clinicians with up-to-date information to assist in antibiotic stewardship and therapeutic decision making.


2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Marissa A. Valentine-King ◽  
Katherine Cisneros ◽  
Margaret O. James ◽  
Robert W. Huigens ◽  
Mary B. Brown

ABSTRACT Escalating levels of antibiotic resistance in mycoplasmas, particularly macrolide resistance in Mycoplasma pneumoniae and M. genitalium, have narrowed our antibiotic arsenal. Further, mycoplasmas lack a cell wall and do not synthesize folic acid, rendering common antibiotics, such as beta-lactams, vancomycin, sulfonamides, and trimethoprim, of no value. To address this shortage, we screened nitroxoline, triclosan, and a library of 20 novel, halogenated phenazine, quinoline, and NH125 analogues against Ureaplasma species and M. hominis clinical isolates from urine. We tested a subset of these compounds (n = 9) against four mycoplasma type strains (M. pneumoniae, M. genitalium, M. hominis, and Ureaplasma urealyticum) using a validated broth microdilution or agar dilution method. Among 72 Ureaplasma species clinical isolates, nitroxoline proved most effective (MIC90, 6.25 µM), followed by an N-arylated NH125 analogue (MIC90, 12.5 µM). NH125 and its analogue had significantly higher MICs against U. urealyticum isolates than against U. parvum isolates, whereas nitroxoline did not. Nitroxoline exhibited bactericidal activity against U. parvum isolates but bacteriostatic activity against the majority of U. urealyticum isolates. Among the type strains, the compounds had the greatest activity against M. pneumoniae and M. genitalium, with 8 (80%) and 5 (71.4%) isolates demonstrating MICs of ≤12.5 µM, respectively. Triclosan also exhibited lower MICs against M. pneumoniae and M. genitalium. Overall, we identified a promising range of quinoline, halogenated phenazine, and NH125 compounds that showed effectiveness against M. pneumoniae and M. genitalium and found that nitroxoline, approved for use outside the United States for the treatment of urinary tract infections, and an N-arylated NH125 analogue demonstrated low MICs against Ureaplasma species isolates.


mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Anna C. Jacobs ◽  
Mitchell G. Thompson ◽  
Chad C. Black ◽  
Jennifer L. Kessler ◽  
Lily P. Clark ◽  
...  

ABSTRACT Acinetobacter baumannii is recognized as an emerging bacterial pathogen because of traits such as prolonged survival in a desiccated state, effective nosocomial transmission, and an inherent ability to acquire antibiotic resistance genes. A pressing need in the field of A. baumannii research is a suitable model strain that is representative of current clinical isolates, is highly virulent in established animal models, and can be genetically manipulated. To identify a suitable strain, a genetically diverse set of recent U.S. military clinical isolates was assessed. Pulsed-field gel electrophoresis and multiplex PCR determined the genetic diversity of 33 A. baumannii isolates. Subsequently, five representative isolates were tested in murine pulmonary and Galleria mellonella models of infection. Infections with one strain, AB5075, were considerably more severe in both animal models than those with other isolates, as there was a significant decrease in survival rates. AB5075 also caused osteomyelitis in a rat open fracture model, while another isolate did not. Additionally, a Tn5 transposon library was successfully generated in AB5075, and the insertion of exogenous genes into the AB5075 chromosome via Tn7 was completed, suggesting that this isolate may be genetically amenable for research purposes. Finally, proof-of-concept experiments with the antibiotic rifampin showed that this strain can be used in animal models to assess therapies under numerous parameters, including survival rates and lung bacterial burden. We propose that AB5075 can serve as a model strain for A. baumannii pathogenesis due to its relatively recent isolation, multidrug resistance, reproducible virulence in animal models, and genetic tractability. IMPORTANCE The incidence of A. baumannii infections has increased over the last decade, and unfortunately, so has antibiotic resistance in this bacterial species. A. baumannii is now responsible for more than 10% of all hospital-acquired infections in the United States and has a >50% mortality rate in patients with sepsis and pneumonia. Most research on the pathogenicity of A. baumannii focused on isolates that are not truly representative of current multidrug-resistant strains isolated from patients. After screening of a panel of isolates in different in vitro and in vivo assays, the strain AB5075 was selected as more suitable for research because of its antibiotic resistance profile and increased virulence in animal models. Moreover, AB5075 is susceptible to tetracycline and hygromycin, which makes it amenable to genetic manipulation. Taken together, these traits make AB5075 a good candidate for use in studying virulence and pathogenicity of this species and testing novel antimicrobials.


2001 ◽  
Vol 45 (1) ◽  
pp. 267-274 ◽  
Author(s):  
Daniel F. Sahm ◽  
Ian A. Critchley ◽  
Laurie J. Kelly ◽  
James A. Karlowsky ◽  
David C. Mayfield ◽  
...  

ABSTRACT Given the propensity for Enterobacteriaceae and clinically significant nonfermentative gram-negative bacilli to acquire antimicrobial resistance, consistent surveillance of the activities of agents commonly prescribed to treat infections arising from these organisms is imperative. This study determined the activities of two fluoroquinolones, levofloxacin and ciprofloxacin, and seven comparative agents against recent clinical isolates ofEnterobacteriaceae, Pseudomonas aeruginosa,Acinetobacter baumannii, and Stenotrophomonas maltophilia using two surveillance strategies: 1) centralized in vitro susceptibility testing of isolates collected from 27 hospital laboratories across the United States and 2) analysis of data from The Surveillance Network Database-USA, an electronic surveillance network comprising more than 200 laboratories nationwide. Regardless of the surveillance method, Enterobacteriaceae,P. aeruginosa, and A. baumannii demonstrated similar rates of susceptibility to levofloxacin and ciprofloxacin. Susceptibilities to the fluoroquinolones approached or exceeded 90% for all Enterobacteriaceae except Providenciaspp. (≤65%). Approximately 70% of P. aeruginosa and 50% of A. baumanii isolates were susceptible to both fluoroquinolones. Among S. maltophilia isolates, 50% more isolates were susceptible to levofloxacin than to ciprofloxacin. Overall, the rate of ceftazidime nonsusceptibility amongEnterobacteriaceae was 8.7%, with fluoroquinolone resistance rates notably higher among ceftazidime-nonsusceptible isolates than ceftazidime-susceptible ones. Multidrug-resistant isolates were present among all species tested but were most prevalent for Klebsiella pneumoniae andEnterobacter cloacae. No gram-negative isolates resistant only to a fluoroquinolone were encountered, regardless of species. Thus, while levofloxacin and ciprofloxacin have maintained potent activity against Enterobacteriaceae, the potential for fluoroquinolone resistance, the apparent association between fluoroquinolone and cephalosporin resistance, and the presence of multidrug resistance in every species examined emphasize the need to maintain active surveillance of resistance patterns among gram-negative bacilli.


2016 ◽  
Vol 60 (10) ◽  
pp. 5640-5648 ◽  
Author(s):  
Vien T. M. Le ◽  
Christine Tkaczyk ◽  
Sally Chau ◽  
Renee L. Rao ◽  
Etyene Castro Dip ◽  
...  

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) causes large-scale epidemics of acute bacterial skin and skin structure infections (ABSSSI) within communities across the United States. Animal models that reproduce ABSSSI as they occur in humans are urgently needed to test new therapeutic strategies. Alpha-toxin plays a critical role in a variety of staphylococcal infection models in mice, but its role in the pathogenesis of ABSSSI remains to be elucidated in rabbits, which are similar to humans in their susceptibility toS. aureussuperantigens and certain bicomponent pore-forming leukocidins. We report here a new rabbit model of ABSSSI and show that those infected with a mutant deficient in expression of alpha-toxin (Δhla) developed a small dermonecrotic lesion, whereas those infected with isogenic USA300 MRSA wild-type or complemented Δhlastrains developed ABSSSI that mimic the severe infections that occur in humans, including the large central dermonecrotic core surrounded by erythema, induration, and marked subcutaneous hemorrhage. More importantly, immunoprophylaxis with MEDI4893*, an anti-alpha-toxin human monoclonal antibody, significantly reduced the severity of disease caused by a USA300 wild-type strain to that caused by the Δhlamutant, indicating that this toxin could be completely neutralized during infection. Thus, this study illustrates a potential high standard for the development of new immunotherapeutic agents in which a toxin-neutralizing antibody provides protection to the same degree achieved with a toxin gene knockout. When MEDI4893* was administered as adjunctive therapy with a subtherapeutic dose of linezolid, the combination was significantly more efficacious than either agent alone in reducing the severity of ABSSSI.


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