Implications Of Antibiotic Resistance Research Articles

AMR mechanisms in L. interrogans serovars: a comprehensive study.

Antimicrobial resistance (AMR) is one of the global health challenges of the 21st century. Data regarding AMR mechanisms in Leptospira interrogans, the causative agents of leptospirosis, have been relatively limited. Therefore, our study aimed to identify resistance genes and explore potential resistance mechanisms specific to particular serovars. We conducted a comprehensive analysis of 98 Leptospira strains, representing 10 common serovars, using whole-genome sequencing (WGS) FASTA files. Employing the PATRIC tool from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), we scrutinized the genomes for AMR genes. Our investigation revealed 32 genes associated with AMR, with 20 key genes consistently prevalent across most strains. Notably, we identified unique efflux pump systems in serovar Pomona, indicating distinctive resistance mechanisms in this serovar. In summary, our findings shed light on the genetic landscape of AMR in Leptospira, uncovering both common and serovar-specific resistance elements. The presence of unique efflux pump systems in serovar Pomona introduces a novel dimension to our understanding of resistance mechanisms. These insights underscore the importance of tailored intervention strategies and collaborative efforts between human and veterinary healthcare professionals, as well as environmental scientists, to address the complex dynamics of leptospirosis and its implications for antibiotic resistance.

Multiple micronutrient deficiencies in early life cause multi-kingdom alterations in the gut microbiome and intrinsic antibiotic resistance genes in mice.

Globally, ~340 million children suffer from multiple micronutrient deficiencies, accompanied by high pathogenic burden and death due to multidrug-resistant bacteria. The microbiome is a reservoir of antimicrobial resistance (AMR), but the implications of undernutrition on the resistome is unclear. Here we used a postnatal mouse model that is deficient in multiple micronutrients (that is, zinc, folate, iron, vitamin A and vitamin B12 deficient) and shotgun metagenomic sequencing of faecal samples to characterize gut microbiome structure and functional potential, and the resistome. Enterobacteriaceae were enriched in micronutrient-deficient mice compared with mice fed an isocaloric experimental control diet. The mycobiome and virome were also altered with multiple micronutrient deficiencies including increased fungal pathogens such as Candida dubliniensis and bacteriophages. Despite being antibiotic naïve, micronutrient deficiency was associated with increased enrichment of genes and gene networks encoded by pathogenic bacteria that are directly or indirectly associated with intrinsic antibiotic resistance. Bacterial oxidative stress was associated with intrinsic antibiotic resistance in these mice. This analysis reveals multi-kingdom alterations in the gut microbiome as a result of co-occurring multiple micronutrient deficiencies and the implications for antibiotic resistance.

The Contribution of the Human Oral Microbiome to Oral Disease: A Review.

The oral microbiome is an emerging field that has been a topic of discussion since the development of next generation sequencing and the implementation of the human microbiome project. This article reviews the current literature surrounding the oral microbiome, briefly highlighting most recent methods of microbiome characterization including cutting edge omics, databases for the microbiome, and areas with current gaps in knowledge. This article also describes reports on microorganisms contained in the oral microbiome which include viruses, archaea, fungi, and bacteria, and provides an in-depth analysis of their significant roles in tissue homeostasis. Finally, we detail key bacteria involved in oral disease, including oral cancer, and the current research surrounding their role in stimulation of inflammatory cytokines, the role of gingival crevicular fluid in periodontal disease, the creation of a network of interactions between microorganisms, the influence of the planktonic microbiome and cospecies biofilms, and the implications of antibiotic resistance. This paper provides a comprehensive literature analysis while also identifying gaps in knowledge to enable future studies to be conducted.

PH variation in medical implant biofilms: Causes, measurements, and its implications for antibiotic resistance.

The advent of implanted medical devices has greatly improved the quality of life and increased longevity. However, infection remains a significant risk because bacteria can colonize device surfaces and form biofilms that are resistant to antibiotics and the host's immune system. Several factors contribute to this resistance, including heterogeneous biochemical and pH microenvironments that can affect bacterial growth and interfere with antibiotic biochemistry; dormant regions in the biofilm with low oxygen, pH, and metabolites; slow bacterial growth and division; and poor antibody penetration through the biofilm, which may also be regions with poor acid product clearance. Measuring pH in biofilms is thus key to understanding their biochemistry and offers potential routes to detect and treat latent infections. This review covers the causes of biofilm pH changes and simulations, general findings of metabolite-dependent pH gradients, methods for measuring pH in biofilms, effects of pH on biofilms, and pH-targeted antimicrobial-based approaches.

Research and market structure: Evidence from an antibiotic-resistant pathogenic outbreak

We provide causal evidence that upstream research shocks impact unconnected downstream product markets. Focusing on the Indian pharmaceutical market, we use a natural experiment involving a publication that identified a pathogenic outbreak involving a carbapenem antibiotic resistant superbug. Consistent with theory, we find that this upstream research shock caused multinational firms selling carbapenem antibiotics in India to reduce their downstream market exposure. Rational antibiotic stewardship implies that we should observe a similar response by domestic Indian firms. Surprisingly, we observe the opposite, domestic Indian firms filled the void in the market left by multinational firms. We confirm this aggregate finding with prescription level data; Indian physicians prescribed fewer focal multinational products relative to domestic firm products. Results are robust to alternate control groups and placebo testing. Implications for antibiotic resistance, global health policy and innovation policy are discussed.

Microbial Multitrophic Communities Drive the Variation of Antibiotic Resistome in the Gut of Soil Woodlice (Crustacea: Isopoda).

Multitrophic communities inhabit in soil faunal gut, including bacteria, fungi, and protists, which have been considered a hidden reservoir for antibiotic resistance genes (ARGs). However, there is a dearth of research focusing on the relationships between ARGs and multitrophic communities in the gut of soil faunas. Here, we studied the contribution of multitrophic communities to variations of ARGs in the soil woodlouse gut. The results revealed diverse and abundant ARGs in the woodlouse gut. Network analysis further exhibited strong connections between key ecological module members and ARGs, suggesting that multitrophic communities in the keystone ecological cluster may play a pivotal role in the variation of ARGs in the woodlouse gut. Moreover, long-term application of sewage sludge significantly altered the woodlice gut resistome and interkingdom communities. The variation portioning analysis indicated that the fungal community has a greater contribution to variations of ARGs than bacterial and protistan communities in the woodlice gut after long-term application of sewage sludge. Together, our results showed that changes in gut microbiota associated with agricultural practices (e.g., sewage sludge application) can largely alter the gut interkingdom network in ecologically relevant soil animals, with implications for antibiotic resistance, which advances our understanding of the microecological drivers of ARGs in terrestrial ecosystem.

Antibiotic resistance during and beyond COVID-19.

Antibiotics underpin the ‘modern medicine’ that has increased life expectancy, leading to societies with sizeable vulnerable elderly populations who have suffered disproportionately during the current COVID-19 pandemic. Governments have responded by shuttering economies, limiting social interactions and refocusing healthcare. There are implications for antibiotic resistance both during and after these events. During spring 2020, COVID-19-stressed ICUs relaxed stewardship, perhaps promoting resistance. Counterpoised to this, more citizens died at home and total hospital antibiotic use declined, reducing selection pressure. Restricted travel and social distancing potentially reduced community import and transmission of resistant bacteria, though hard data are lacking. The future depends on the vaccines now being deployed. Unequivocal vaccine success should allow a swift return to normality. Vaccine failure followed by extended and successful non-pharmaceutical suppression may lead to the same point, but only after some delay, and with indefinite travel restrictions; sustainability is doubtful. Alternatively, failure of vaccines and control measures may prompt acceptance that we must live with the virus, as in the prolonged 1889–94 ‘influenza’ (or coronavirus OC43) pandemic. Vaccine failure scenarios, particularly those accepting ‘learning to live with the virus’, favour increased outpatient management of non-COVID-19 infections using oral and long t½ antibiotics. Ultimately, all models—except those envisaging societal collapse—suggest that COVID-19 will be controlled and that hospitals will revert to pre-2020 patterns with a large backlog of non-COVID-19 patients awaiting treatment. Clearing this will increase workloads, stresses, nosocomial infections, antibiotic use and resistance. New antibiotics, including cefiderocol, are part of the answer. The prescribing information for cefiderocol is available at: https://shionogi-eu-content.com/gb/fetcroja/pi.

Antibiotic Stewardship for Ambulatory Urological Procedures: Cystoscopy and Vasectomy.

We evaluated physician adherence to antibiotic stewardship for outpatient cystoscopy and vasectomy, which are associated with a low risk of infection and for which prophylactic antibiotics are not routinely recommended. We used Truven Health MarketScan® data to identify individuals who underwent diagnostic cystoscopy or vasectomy between 2009 and 2015. Prophylactic antibiotic use was captured within a 30-day preprocedural window for oral and a 24-hour preprocedural window for parenteral medication, respectively. We assessed demographic and clinical characteristics such as geographic location as possible covariates impacting preprocedural antibiotic use. Trends in antibiotic use and the impact of covariates were determined using logistic regression models with SAS® v9.4 software. Significance was set as 2-tailed p <0.05. During the study period 1,060,199 cystoscopy and 433,013 vasectomy claims were processed. Prophylactic antibiotics were used in 38% of all cystoscopies and 16% of all vasectomies. Antibiotic use increased throughout the study period for cystoscopy (34.9% to 45.2%, p=0.002) and vasectomy (15.8% to 19.5%, p=0.032). On multivariable analysis younger age and geographic residence in the South were the most important predictors of antimicrobial prophylaxis use for cystoscopy while older age, higher Charlson comorbidity index score and geographic residence in the South were associated with an increased likelihood of prophylactic antibiotic use for vasectomy. Despite evidence-based recommendations against routine prophylactic antibiotics for uncomplicated office procedures like cystoscopy and vasectomy, antibiotic use has increased over time. Overuse of antibiotic prophylaxis has implications for antibiotic resistance and changes in normal microbial flora.

Projected impact and cost-effectiveness of community-based versus targeted azithromycin administration strategies for reducing child mortality in sub-Saharan Africa.

Trials of mass drug administration (MDA) of azithromycin (AZM) report reductions in child mortality in sub-Saharan Africa (SSA). AZM targeted to high-risk children may preserve benefit while minimizing antibiotic exposure. We modeled the cost-effectiveness of MDA to children 1-59 months of age, MDA to children 1-5 months of age, AZM administered at hospital discharge, and the combination of MDA and post-discharge AZM. Models employed a payer perspective with a 1-year time horizon. Cost-effectiveness was presented as cost per DALY averted and death averted, with probabilistic sensitivity analyses. The model included parameters for macrolide resistance, adverse events, hospitalization, and mortality sourced from published data. Assuming a base-case 1.64% mortality risk among children 1-59 months old, 3.1% among children 1-5 months old, 4.4% mortality risk post-discharge, and 13.5% mortality reduction per trial data, post-discharge AZM would avert ~45,000 deaths, at a cost of $2.84/DALY (95% uncertainty interval [UI]: 1.71-5.57) averted. MDA to only children 1-5 months old would avert ~186,000 deaths at a cost of $4.89/DALY averted (95% UI: 2.88-11.42), MDA to all under-5 children would avert ~267,000 deaths a cost of $14.26/DALY averted (95% UI: 8.72-27.08). Cost-effectiveness decreased with presumed diminished efficacy due to macrolide resistance. Targeting AZM to children at highest risk of death may be an antibiotic-sparing and cost-effective, or even cost-saving, strategy to reduce child mortality. However, targeted AZM averts fewer absolute deaths and may not reach all children who would benefit. Any AZM administration decision must consider implications for antibiotic resistance.

Antibiotic Use by Small-Scale Farmers for Freshwater Aquaculture in the Upper Mekong Delta, Vietnam.

This study describes antibiotic use by small-scale freshwater aquaculture farmers in the upper Mekong Delta in southwestern Vietnam and the knowledge and practices surrounding the cause and prevention of aquaculture disease in that region. Forty five farmers were included in the study, of which 19 (42%) cultivated tilapia Oreochromis spp., 13 (29%) Striped Catfish Pangasianodon hypophthalmus and 13 (29%) giant river prawns Macrobrachium rosenbergii. Antibiotics were used by farmers of tilapia and Striped Catfish (84% and 69% of farmers, respectively), but not by any of the prawn farmers. Most farmers (72%) used antibiotics for around 3d when treating diseases, depending on the farmers' economic means and whether the fish recovered, as judged by the farmer. If farmers perceived that the antibiotic treatment had failed, the most common response was to change to another type of antibiotic. Some farmers also used antibiotics in the absence of clinical symptoms as a preventive measure. In the absence of rapid, cost-effective diagnostics, the likelihood for the incorrect use of antibiotics is high, which has implications for antibiotic resistance. Moreover, the sequential use of different antibiotics following therapeutic failure is a risk factor for the emergence of resistance. All farmers that were surveyed were aware of the risks associated with antibiotic use. This may lead to successful intervention toward reduced antibiotic use in freshwater fish farming in Vietnam.

Cost-Effectiveness Analysis of the Use of Point-of-Care C-Reactive Protein Testing to Reduce Antibiotic Prescribing in Primary Care.

More appropriate and measured use of antibiotics may be achieved using point-of-care (POC) C-reactive protein (CRP) testing, but there is limited evidence of cost-effectiveness in routine practice. A decision analytic model was developed to estimate the cost-effectiveness of testing, compared with standard care, in adults presenting in primary care with symptoms of acute respiratory tract infection (ARTI). Analyses considered (1) pragmatic use of testing, reflective of routine clinical practice, and (2) testing according to clinical guidelines. Threshold and scenario analysis were performed to identify cost-effective scenarios. In patients with symptoms of ARTI and based on routine practice, the incremental cost-effectiveness ratios of CRP testing were £19,705 per quality-adjusted-life-year (QALY) gained and £16.07 per antibiotic prescription avoided. Following clinical guideline, CRP testing in patients with lower respiratory tract infections (LRTIs) cost £4390 per QALY gained and £9.31 per antibiotic prescription avoided. At a threshold of £20,000 per QALY, the probabilities of POC CRP testing being cost-effective were 0.49 (ARTI) and 0.84 (LRTI). POC CRP testing as implemented in routine practice is appreciably less cost-effective than when adhering to clinical guidelines. The implications for antibiotic resistance and Clostridium difficile infection warrant further investigation.

MP02-04 ANTIBIOTIC STEWARDSHIP FOR AMBULATORY UROLOGIC PROCEDURES: CYSTOSCOPY AND VASECTOMY

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I1 Apr 2018MP02-04 ANTIBIOTIC STEWARDSHIP FOR AMBULATORY UROLOGIC PROCEDURES: CYSTOSCOPY AND VASECTOMY Mark Henry, Dattatraya Patil, Christopher Filson, and Akanksha Mehta Mark HenryMark Henry More articles by this author , Dattatraya PatilDattatraya Patil More articles by this author , Christopher FilsonChristopher Filson More articles by this author , and Akanksha MehtaAkanksha Mehta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.130AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We sought to evaluate physician adherence to the AUA Best Practice Statement on antimicrobial prophylaxis, in order to assess physician interest in antibiotic stewardship. Pre-procedural prophylactic antibiotics are not routinely recommended for uncomplicated cystoscopy and vasectomy, given the low risk of infection associated with these commonly performed procedures. METHODS We used 2009-2015 Truven Health MarketScan Data to identify men who underwent either diagnostic cystoscopy or vasectomy using CPT 52000 and CPT55250/V2652 codes, respectively. Antibiotics associated with a procedure were captured within a 30-day pre-procedural window for oral, and 24 hour pre-procedural window for parenteral medication, respectively. Antibiotics were identified using National Drug Code numbers submitted for pharmaceutical & outpatient service claims. We assessed relevant patient characteristics (age, Charlson Comorbidity Index (CCI), U.S. Census Bureau region, year of procedure, health plan type, and metropolitan service area) that could potentially impact antibiotic use. Trends in antibiotic use, and the impact of covariates on antibiotics use was determined using linear regression models with SAS v9.4 software. Significance was set as two-tailed p-values <0.05. RESULTS 1,060,199 cystoscopy and 433,013 vasectomy claims were processed during the study period. Prophylactic antibiotics were utilized in 38% of all cystoscopies and 16% of all vasectomies. Antibiotic use increased throughout the study period for both cystoscopy (34.9% to 45.2%, p = 0.002) and vasectomy (15.8% to 19.5%, p = 0.032). Increasing age and CCI were associated with decreased likelihood of prophylactic antibiotics for cystoscopy, while increasing age and CCI were associated with an increased likelihood of prophylactic antibiotics for vasectomy. Geographic region was also found to impact the likelihood of antibiotic use; with Northcentral as the reference point, antibiotic use for both cystoscopy and vasectomy was highest is the South (OR 1.21 and 1.44, respectively), and lowest in the Northeast for cystoscopy (OR 0.85) and West for vasectomy (OR 0.89) (p < 0.001). CONCLUSIONS Despite evidence-based recommendations against routine prophylactic antibiotics for uncomplicated office procedures like cystoscopy and vasectomy, antibiotic use has nevertheless increased overtime, with implications for antibiotic resistance and changes in normal microbial flora. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e12-e13 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Mark Henry More articles by this author Dattatraya Patil More articles by this author Christopher Filson More articles by this author Akanksha Mehta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Methicillin-Resistant Staphylococcus aureus: A Pharmacotherapy Primer

Objectives1.Recommend appropriate antimicrobial regimens for a given MRSA infection.2.Describe the mechanisms, dosing, and monitoring parameters of antibiotics used to treat MRSA infections.3.Explain the mechanisms and implications of antibiotic resistance among Staphylococcus aureus. 1.Recommend appropriate antimicrobial regimens for a given MRSA infection.2.Describe the mechanisms, dosing, and monitoring parameters of antibiotics used to treat MRSA infections.3.Explain the mechanisms and implications of antibiotic resistance among Staphylococcus aureus. Staphylococcus aureus is a common pathogen that can infect a variety of body sites, causing skin and soft tissue infections (SSTIs), bacteremia and endocarditis, bone and joint infections, pneumonia, and infections of the central nervous system (Liu et al., 2011Liu C. Bayer A. Cosgrove S.E. Daum R.S. Fridkin S.K. Gorwitz R.J. Chambers H.F. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.Clinical Infectious Diseases. 2011; 53: e18-e55Crossref Scopus (1896) Google Scholar, Lowy, 1998Lowy F.D. Staphylococcus aureus infections.The New England Journal of Medicine. 1998; 339: 520-532Crossref PubMed Scopus (4617) Google Scholar). A working knowledge of the management of S. aureus infections is important to provide prompt and optimal care, because S. aureus is associated with significant morbidity and mortality and is highly prevalent in both hospital and community settings, and because treatment involves a variety of antibiotics with different mechanisms and toxicities. Antibiotic selection for children is further complicated by unique toxicities and a relative lack of dosing guidance and supporting data. Staphylococci are Gram-positive cocci that grow most commonly in irregular clusters. All Staphylococcus species typically produce the enzyme catalase and are facultative anaerobes (Que and Moreillon, 2015Que Y. Moreillon P. Staphylococcus aureus (including staphylococcal toxic shock).in: Mandell G.L. Bennett J.E. Dolin R. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Saunders, Elsevier Inc, Philadelphia, PA2015Google Scholar). S. aureus may be differentiated from other Staphylococcus species by its production of the enzyme coagulase and is referred to as “coagulase-positive.” Aside from S. aureus, all other staphylococci found in humans are coagulase-negative and, when pathogenic, are generally less virulent (Que and Moreillon, 2015Que Y. Moreillon P. Staphylococcus aureus (including staphylococcal toxic shock).in: Mandell G.L. Bennett J.E. Dolin R. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Saunders, Elsevier Inc, Philadelphia, PA2015Google Scholar, Rupp and Fey, 2015Rupp M.E. Fey P.D. Staphylococcus epidermidis and other coagulase- negative staphylococci.in: Mandell G.L. Bennett J.E. Dolin R. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Saunders, Elsevier Inc, Philadelphia, PA2015: 2272-2282Google Scholar). S. aureus commonly colonizes skin and mucosa. Asymptomatic nasal colonization, occurring in approximately 30% of the population, has contributed to the spread and persistence of S. aureus (Chambers and DeLeo, 2009Chambers H.F. DeLeo F.R. Waves of resistance: Staphylococcus aureus in the antibiotic era.Nature Reviews Microbiology. 2009; 7: 629-641Crossref PubMed Scopus (1725) Google Scholar). Such persistence, as well as enhanced pathogenesis, may also be attributed to a variety of microbiological factors. Surface adhesions and biofilm production promote adherence to host proteins and medical devices (Que and Moreillon, 2015Que Y. Moreillon P. Staphylococcus aureus (including staphylococcal toxic shock).in: Mandell G.L. Bennett J.E. Dolin R. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Saunders, Elsevier Inc, Philadelphia, PA2015Google Scholar). Additionally, S. aureus produces a number of enzymes and toxins including hemolysins and the Panton-Valentine leukocidin that may be associated with more severe infections (Chambers and DeLeo, 2009Chambers H.F. DeLeo F.R. Waves of resistance: Staphylococcus aureus in the antibiotic era.Nature Reviews Microbiology. 2009; 7: 629-641Crossref PubMed Scopus (1725) Google Scholar, Que and Moreillon, 2015Que Y. Moreillon P. Staphylococcus aureus (including staphylococcal toxic shock).in: Mandell G.L. Bennett J.E. Dolin R. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Saunders, Elsevier Inc, Philadelphia, PA2015Google Scholar). Historically, all strains of S. aureus were susceptible to penicillin, but development of penicillin resistance, followed by methicillin resistance, spread during the 1970s and 1980s, followed by the substantial presence of methicillin-resistant S. aureus (MRSA) in both hospital and community settings by the 1990s (Chambers and DeLeo, 2009Chambers H.F. DeLeo F.R. Waves of resistance: Staphylococcus aureus in the antibiotic era.Nature Reviews Microbiology. 2009; 7: 629-641Crossref PubMed Scopus (1725) Google Scholar, Iwamoto et al., 2013Iwamoto M. Mu Y. Lynfield R. Bulens S.N. Nadle J. Aragon D. Lessa F.C. Trends in invasive methicillin-resistant Staphylococcus aureus infections.Pediatrics. 2013; 132: e817-e824Crossref PubMed Scopus (92) Google Scholar). MRSA continues to represent a significant health care challenge today. Beyond the type of infection caused by MRSA, antibiotic selection also depends on the patient's overall clinical status and severity of infection. For example, MRSA SSTIs may range from uncomplicated impetigo likely to resolve without any antimicrobial therapy to a life-threatening extensive infection progressing to toxic shock needing broad-spectrum antibiotics. When managing bacteremia, a positive blood culture result alone is insufficient to guide antibiotic selection, and the source of the bloodstream infection must be considered. For example, rapidly resolving bacteremia attributable to an SSTI or acute hematogenous osteomyelitis (AHO) is treated differently than complicated bacteremia with an intravascular source of infection as in endocarditis. Although the following sections focus on pharmacotherapy, many nonpharmacologic interventions such as radiographic imaging, incision and drainage, removal of infected hardware, and identification and management of any predisposing conditions like immune system deficiencies are critical to successful treatment. Antibiotic options that may be suitable for each infection type reviewed below are also summarized in Box 1.When managing bacteremia, a positive blood culture result alone is insufficient to guide antibiotic selection…Box 1Antibiotic options for selected MRSA infectionsSkin and skin structure infections•Clindamycin•SMX-TMP•Vancomycin•Linezolid•Ceftarolinea•Daptomycinb•DoxycyclinecOsteomyelitis•Clindamycin•Vancomycin•Daptomycinb•LinezolidPneumonia•Vancomycin•Linezolid•Clindamycin•CeftarolineaCNS infection•Vancomycin•Linezolid•SMX-TMPBacteremia and infective endocarditis (IE)•Vancomycin (+rifampin + gentamicin for prosthetic valve IE)•Daptomycinb•CeftarolineaNote. CNS, central nervous system; FDA, U.S. Food and Drug Administration; MRSA, methicillin-resistant Staphylococcus aureus; SMX-TMP, sulfamethoxazole/trimethoprim.aCeftaroline is approved only for use in skin and soft tissue infections and non-MRSA community acquired pneumonia.bNot FDA-approved for use in children.cAvoid use in children younger than 8 years of age. When managing bacteremia, a positive blood culture result alone is insufficient to guide antibiotic selection… Skin and skin structure infections•Clindamycin•SMX-TMP•Vancomycin•Linezolid•Ceftarolinea•Daptomycinb•DoxycyclinecOsteomyelitis•Clindamycin•Vancomycin•Daptomycinb•LinezolidPneumonia•Vancomycin•Linezolid•Clindamycin•CeftarolineaCNS infection•Vancomycin•Linezolid•SMX-TMPBacteremia and infective endocarditis (IE)•Vancomycin (+rifampin + gentamicin for prosthetic valve IE)•Daptomycinb•Ceftarolinea Note. CNS, central nervous system; FDA, U.S. Food and Drug Administration; MRSA, methicillin-resistant Staphylococcus aureus; SMX-TMP, sulfamethoxazole/trimethoprim. aCeftaroline is approved only for use in skin and soft tissue infections and non-MRSA community acquired pneumonia. bNot FDA-approved for use in children. cAvoid use in children younger than 8 years of age. Purulent skin infection, or the presence of pus within an abscess or other wound, is suggestive of a staphylococcal infection, and drainage should be sent for culture and susceptibility testing. Current guidelines for SSTI management recommend topical mupirocin for bullous and nonbullous impetigo, but systemic therapy is recommended in the setting of an outbreak for patients with multiple lesions (Stevens et al., 2014Stevens D.L. Bisno A.L. Chambers H.F. Dellinger E.P. Goldstein E.J. Gorbach S.L. Wade J.C. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America.Clinical Infectious Diseases. 2014; 59: e10-e52Crossref PubMed Scopus (998) Google Scholar). Systemic antibiotic therapy is additionally recommended for more complicated or extensive skin abscesses, including failure to improve after incision and drainage, associated septic phlebitis or spreading cellulitis, incomplete drainage, or systemic illness (Liu et al., 2011Liu C. Bayer A. Cosgrove S.E. Daum R.S. Fridkin S.K. Gorwitz R.J. Chambers H.F. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.Clinical Infectious Diseases. 2011; 53: e18-e55Crossref Scopus (1896) Google Scholar). In the outpatient setting, a variety of oral antibiotics may be used for MRSA SSTIs, including sulfamethoxazole/trimethoprim (SMX-TMP), clindamycin, doxycycline, or linezolid. Antibiotic selection requires consideration of regional or institutional susceptibility patterns, patient age, and drug costs and toxicities. For example, doxycycline is not used in children under 8 years of age, and linezolid is more expensive than other treatment options. Drug-specific considerations are reviewed in greater detail later. Children hospitalized for a complicated SSTI should be treated with vancomycin, particularly in the setting of bacteremia, hemodynamic instability, or other signs of systemic illness. Clindamycin may also be used empirically for clinically stable patients without persistent bacteremia or endocarditis, if the institutional rate of clindamycin resistance among S. aureus is less than 10% to 15%. Staphylococcal scalded skin syndrome and toxic shock syndrome (TSS) are toxin-mediated disease states. Although TSS typically presents with a rash early and later desquamation, it is a multisystem illness, including hypotension and multiorgan failure. TSS has been associated with tampon use but may present in association with skin lesions or surgery, or without any clear infection source (Kimberlin et al., 2015Kimberlin D.W. Brady M.T. Jackson M.A. Long S.S. Staphylococcal infections. American Academy of Pediatrics, Elk Grove Village, IL2015Google Scholar). In addition to supportive care measures like hydration and vasopressor therapy, prompt antibiotic treatment with a cell wall active agent, typically vancomycin, in combination with a protein synthesis inhibitor like clindamycin to reduce toxin production is critical (Kimberlin et al., 2015Kimberlin D.W. Brady M.T. Jackson M.A. Long S.S. Staphylococcal infections. American Academy of Pediatrics, Elk Grove Village, IL2015Google Scholar). Because staphylococcal SSTIs often recur in patients and family members, there is interest in eradicating asymptomatic colonization or carriage of S. aureus as a means of reducing spread and continued infections (Creech et al., 2015Creech C.B. Al-Zubeidi D.N. Fritz S.A. Prevention of recurrent staphylococcal skin infections.Infectious Disease Clinics of North America. 2015; 29: 429-464Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar). This practice is referred to as decolonization, and it most often involves topical antimicrobial therapy including intranasal mupirocin and chlorhexidine washes (Stevens et al., 2014Stevens D.L. Bisno A.L. Chambers H.F. Dellinger E.P. Goldstein E.J. Gorbach S.L. Wade J.C. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America.Clinical Infectious Diseases. 2014; 59: e10-e52Crossref PubMed Scopus (998) Google Scholar). Reported outcomes of topical MRSA decolonization are varied. Although most studies comparing decolonization to either placebo or standard hygiene practices identified greater S. aureus eradication in the treatment groups, the impact on later incidence of SSTI was varied and not consistently reduced among patients who had undergone decolonization (Ellis et al., 2007Ellis M.W. Griffith M.E. Dooley D.P. McLean J.C. Jorgensen J.H. Patterson J.E. Hospenthal D.R. Targeted intranasal mupirocin to prevent colonization and infection by community-associated methicillin-resistant Staphylococcus aureus strains in soldiers: A cluster randomized controlled trial.Antimicrobial Agents and Chemotherapy. 2007; 51: 3591-3598Crossref PubMed Scopus (112) Google Scholar, Fritz et al., 2011Fritz S.A. Camins B.C. Eisenstein K.A. Fritz J.M. Epplin E.K. Burnham C.A. Storch G.A. Effectiveness of measures to eradicate Staphylococcus aureus carriage in patients with community-associated skin and soft-tissue infections: A randomized trial.Infection Control & Hospital Epidemiology. 2011; 32: 872-880Crossref PubMed Scopus (104) Google Scholar, Raz et al., 1996Raz R. Miron D. Colodner R. Staler Z. Samara Z. Keness Y. A 1-year trial of nasal mupirocin in the prevention of recurrent staphylococcal nasal colonization and skin infection.Archives of Internal Medicine. 1996; 10: 1109-1112Crossref Google Scholar, Whitman et al., 2010Whitman T.J. Herlihy R.K. Schlett C.D. Murray P.R. Grandits G.A. Ganesan A. Tribble D.R. Chlorhexidine-impregnated cloths to prevent skin and soft-tissue infection in Marine recruits: A cluster-randomized, double-blind, controlled effectiveness trial.Infection Control & Hospital Epidemiology. 2010; 31: 1207-1215Crossref PubMed Scopus (46) Google Scholar). Additionally, later development of resistance to topical therapies has been reported (Fritz et al., 2013Fritz S.A. Hogan P.G. Camins B.C. Ainsworth A.J. Patrick C. Martin M.S. Burnham C.A. Mupirocin and chlorhexidine resistance in Staphylococcus aureus in patients with community-onset skin and soft tissue infections.Antimicrobial Agents and Chemotherapy. 2013; 57: 559-568Crossref PubMed Scopus (107) Google Scholar, McNeil et al., 2011McNeil J.C. Hulten K.G. Kaplan S.L. Mason E.O. Mupirocin resistance in Staphylococcus aureus causing recurrent skin and soft tissue infections in children.Antimicrobial Agents and Chemotherapy. 2011; 55: 2431-2433Crossref PubMed Scopus (48) Google Scholar, McNeil et al., 2013McNeil J.C. Hulten K.G. Kaplan S.L. Mahoney D.H. Mason E.O. Staphylococcus aureus infections in pediatric oncology patients: High rates of antimicrobial resistance, antiseptic tolerance and complications.Pediatric Infectious Diseases Journal. 2013; 32: 124-128Crossref PubMed Scopus (46) Google Scholar) but was not confirmed in a recent randomized controlled trial (Hayden et al., 2016Hayden M.K. Lolans K. Haffenreffer K. Avery T.R. Kleinman K. Li H. Huang S.S. Chlorhexidine and mupirocin susceptibility of methicillin-resistant Staphylococcus aureus isolates in the REDUCE-MRSA trial.Journal of Clinical Microbiology. 2016; 54: 2735-2742Crossref PubMed Scopus (50) Google Scholar). Consistent with existing literature and current national consensus guidelines, decolonization should be prioritized for patients with recurrent SSTIs or for settings where S. aureus is continually being spread among household members (Creech et al., 2015Creech C.B. Al-Zubeidi D.N. Fritz S.A. Prevention of recurrent staphylococcal skin infections.Infectious Disease Clinics of North America. 2015; 29: 429-464Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar, Liu et al., 2011Liu C. Bayer A. Cosgrove S.E. Daum R.S. Fridkin S.K. Gorwitz R.J. Chambers H.F. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.Clinical Infectious Diseases. 2011; 53: e18-e55Crossref Scopus (1896) Google Scholar, Stevens et al., 2014Stevens D.L. Bisno A.L. Chambers H.F. Dellinger E.P. Goldstein E.J. Gorbach S.L. Wade J.C. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America.Clinical Infectious Diseases. 2014; 59: e10-e52Crossref PubMed Scopus (998) Google Scholar). MRSA pneumonia is most commonly a health care–associated or hospital-acquired infection and is rarely implicated in community-acquired pneumonia (CAP). MRSA CAP has been described in association with previous or concurrent influenza and among patients with diabetes or those requiring hemodialysis (Self et al., 2016Self W.H. Wunderink R.G. Williams D.J. Zhu Y. Anderson E.J. Balk R.A. Grijalva C.G. Staphylococcus aureus community-acquired pneumonia: prevalence, clinical characteristics, and outcomes.Clinical Infectious Diseases. 2016; 63: 300-309Crossref PubMed Scopus (103) Google Scholar). Although not confirmed in a recent case–control study to be unique to MRSA, it remains prudent to empirically cover MRSA in severe cases of CAP, such as patients requiring admission to an intensive care unit or presenting with empyema or cavitation on radiograph (Liu et al., 2011Liu C. Bayer A. Cosgrove S.E. Daum R.S. Fridkin S.K. Gorwitz R.J. Chambers H.F. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.Clinical Infectious Diseases. 2011; 53: e18-e55Crossref Scopus (1896) Google Scholar, Self et al., 2016Self W.H. Wunderink R.G. Williams D.J. Zhu Y. Anderson E.J. Balk R.A. Grijalva C.G. Staphylococcus aureus community-acquired pneumonia: prevalence, clinical characteristics, and outcomes.Clinical Infectious Diseases. 2016; 63: 300-309Crossref PubMed Scopus (103) Google Scholar). The recommended treatment of MRSA pneumonia in children is vancomycin, with the alternative option of clindamycin for clinically stable patients without persistent bacteremia at practice at sites where less than 10% of S. aureus are resistant to clindamycin. Other treatment options include linezolid or, potentially, ceftaroline. Recent consensus guidelines for the treatment of hospital-acquired pneumonia in adults recommend only vancomycin or linezolid for the empiric treatment of MRSA pneumonia (Kalil et al., 2016Kalil A.C. Metersky M.L. Klompas M. Muscedere J. Sweeney D.A. Palmer L.B. Brozek J.L. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society.Clinical Infectious Diseases. 2016; 63: e61-e111Crossref PubMed Scopus (1707) Google Scholar). Daptomycin serves no role in the management of pneumonia because it is inactivated by pulmonary surfactant (Merck & Co., Inc, 2015Merck & Co., IncCubicin [package insert]. Author, Whitehouse Station, NJ2015Google Scholar). CAP in children is typically treated for 7 to 10 days, although longer treatment courses may be prescribed depending on the severity and improvement of the infection. Acute hematogenous osteomyelitis (AHO) is common in young children because of open epiphyses with capillaries providing nutrients to growing bones. A transient bacteremia can lead to a bone infection more easily in a child than in an adult (Gutierrez, 2012Gutierrez K. Osteomyelitis.in: Long S.S. Pickering L.K. Prober C.G. Principles and practice of pediatric infectious diseases. Elsevier Inc, Philadelphia, PA2012: 469-477Google Scholar). Osteomyelitis may also occur secondary to injury like an open fracture or puncture wound, or an untreated local infection such as a periodontal abscess progressing to facial osteomyelitis. In addition to surgical debridement when indicated (particularly in the setting of septic arthritis), treatment involves either vancomycin or clindamycin. Current guidelines recommend either vancomycin or clindamycin, with the same stipulations as described for clindamycin with respect to patient status, blood culture results, and institutional susceptibility data. Linezolid, SMX-TMP, and daptomycin are additional alternatives. Daptomycin is currently being studied for AHO in children, and investigational dosing regimens are reviewed later. The recommended duration of therapy for MRSA osteomyelitis is dependent on patient progress, often involving repeated imaging, monitoring of C-reactive protein concentrations, and evaluation of clinical response. At a minimum, septic arthritis is typically treated for 3 to 4 weeks and AHO for 4 to 6 weeks (Erickson et al., 2016Erickson C.M. Sue P.K. Stewart K. Thomas M.I. Lindsay E.A. Jo C. Copley L.A.B. Pediatric Infectious Diseases Journal. 2016; 35: 1092-1096Crossref PubMed Scopus (5) Google Scholar, Keren et al., 2015Keren R. Shah S.S. Srivastava R. Rangel S. Bendel-Stenzel M. Harik N. Parker A. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children.The Journal of the American Medical Association Pediatrics. 2015; 162: 120-128Google Scholar, Liu et al., 2011Liu C. Bayer A. Cosgrove S.E. Daum R.S. Fridkin S.K. Gorwitz R.J. Chambers H.F. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.Clinical Infectious Diseases. 2011; 53: e18-e55Crossref Scopus (1896) Google Scholar). These prolonged durations of therapy may require long-term intravenous (IV) antibiotics, but equivalent outcomes have been observed after oral treatment with clindamycin (Erickson et al., 2016Erickson C.M. Sue P.K. Stewart K. Thomas M.I. Lindsay E.A. Jo C. Copley L.A.B. Pediatric Infectious Diseases Journal. 2016; 35: 1092-1096Crossref PubMed Scopus (5) Google Scholar, Keren et al., 2015Keren R. Shah S.S. Srivastava R. Rangel S. Bendel-Stenzel M. Harik N. Parker A. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children.The Journal of the American Medical Association Pediatrics. 2015; 162: 120-128Google Scholar) without the inconvenience or associated risks of IV treatment like thrombosis or infection. Infections described earlier like SSTIs, pneumonia, or bone and joint infections may present with transient bacteremia, but bloodstream infections related to intravascular catheters or endovascular tissue represent unique disease states requiring different approaches to management. Bloodstream infections are a common complication of intravascular catheters, and management depends on characteristics of both the patient and the infected line. In contrast to abscesses, which can be promptly drained, or short-term catheter lines, which can be readily removed, source control is a more complicated treatment decision in the setting of long-term central venous IV catheters. Many children depend on this type of IV access for survival, such as those with short bowel syndrome requiring parenteral nutrition or those with renal failure requiring hemodialysis. In these patients, the availability and accessibility of alternative catheter insertion sites must be carefully considered in addition to patient, pathogen, and infection characteristics, and greater efforts to salvage catheters may be warranted. To retain an infected catheter, sterilization must be achieved through strategies like infusing IV antibiotics directly through the infected catheter or locking the IV line with antibiotics or ethanol (Mermel et al., 2009Mermel L.A. Allon M. Bouza E. Craven D.E. Flynn P. O'Grady N.P. Warren D.K. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America.Clinical Infectious Diseases. 2009; 49: 1-45Crossref PubMed Scopus (2342) Google Scholar, Oliveria et al., 2012Oliveria C. Nasr A. Brindle M. Wales P.W. Ethanol locks to prevent catheter- related bloodstream infections in parenteral nutrition: A meta-analysis.Pediatrics. 2012; 129: 318-329Crossref PubMed Scopus (138) Google Scholar, Pitts et al., 2014Pitts S. Bergamo D. Cartaya C. Gore B. Efficacy in the reduction of central line-associated bloodstream infection in a patient with intestinal failure: An ethanol lock pediatric case study.Journal of the Association for Vascular Access. 2014; 4: 217-220Abstract Full Text Full Text PDF Scopus (1) Google Scholar, Restrepo et al., 2015Restrepo D. Laconi N.S. Alcantar N.A. West L.A. Buttice A.L. Patel S. Kayton M.L. Inhibition of heparin precipitation, bacterial growth, and fungal growth with a combined isopopanol-ethanol locking solution for vascular access devices.Journal of Pediatric Surgery. 2015; 50: 428-477Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, Schoot et al., 2015Schoot R.A. van Ommen C.H. Stijnen T. Tissing W.J.E. Michiels E. Abbink F.C.H. van de Wetering M.D. Prevention of central venous catheter-associated bloodstream infections in paeditric oncology patients using 70% ethanol locks: A randomized controlled mutli-centre trial.European Journal of Cancer. 2015; 51: 2021-2038Google Scholar). In general, MRSA intravascular catheter-related bloodstream infection may be treated for as short as 2 weeks after the first negative blood culture result if fever and bacteremia resolve within 72 hours of treatment and the child does not have comorbid conditions like diabetes, immunosuppression, neutropenia, intravascular prosthetic material (e.g., artificial valve or pacemaker), evidence of endocarditis, or suppurative thrombophlebitis. Children with these complicating features, or more severe or persistent infections, may require 4 to 6 weeks of antibiotics (Mermel et al., 2009Mermel L.A. Allon M. Bouza E. Craven D.E. Flynn P. O'Grady N.P. Warren D.K. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America.Clinical Infectious Diseases. 2009; 49: 1-45Crossref PubMed Scopus (2342) Google Scholar). Infective endocarditis is a serious infection involving the endocardium, or innermost layer of the heart (Cabell et al., 2003Cabell C.H. Abrutyn E. Karchmer A.W. Bacterial endocarditis: the disease, treatment, and prevention.Circulation. 2003; 107: e185-e187PubMed Google Scholar). Treatment of MRSA endocarditis requires prolonged treatment, typically 6 weeks, with high doses of antibiotics to overcome the characteristically high bacterial inocula and biofilm formation that allows for slower bacterial growth and division, resulting in reduced antibiotic effectiveness (Baltimore et al., 2015Baltimore R.S. Gewitz M. Baddour L.M. Beerman L.B. Jackson M. Lockhart P.B. Willoughby Jr., R. Infective endocarditis in childhood: 2015 update.Circulation. 2015; 132: 1487-1515Crossref PubMed Scopus (186) Google Scholar). Vancomycin remains the preferred agent for management of MRSA bacteremia and endocarditis. Potential alternative options include daptomycin or ceftaroline. Clindamycin and linezolid should be avoided because they exert bacteriostatic effects against S. aureus, and bactericidal agents are generally preferred in this clinical situation (Baltimore et al., 2015Baltimore R.S. Gewitz M. Baddour L.M. Beerman L.B. Jackson M. Lockhart P.B. Willoughby Jr., R. Infective endocarditis in childhood: 2015 update.Circulation. 2015; 132: 1487-1515Crossref PubMed Scopus (186) Google Scholar, Liu et al., 2011Liu C. Bayer A. Cosgrove S.E. Daum R.S. Fridkin S.K. Gorwitz R.J. Chambers H.F. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.Clinical Infectious Diseases. 2011; 53: e18-e55Crossref Scopus (1896) Google Scholar). When treating MRSA endocarditis for patients with prosthetic cardiac material, vancomycin should be combined with both gentamicin for synergistic bacterial killing and rifampin for enhanced biofilm penetration (Baltimore et al., 2015Baltimore R.S. Gewitz M. Baddour L.M. Beerman L.B. Jackson M. Lockhart P.B. Willoughby Jr., R. Infective endocarditis in childhood: 2015 update.Circulation. 2015; 132: 1487-1515Crossref PubMed Scopus (186) Google Scholar, Hall Snyder et al., 2015Hall Snyder A.D. Vidaillac C. Rose W. McRoberts J.P. Rybak M.J. Evaluation of high-dose daptomycin versus vancomycin alone or combined with clarithromycin or rifampin against Staphylococcus aureus and S. epidermidis in a novel in vitro PK/PD model of bacterial biofilm.Infectious Diseases and Therapy. 2015; 4: 51-65Crossref PubMed Scopus (32) Google Scholar). Although MRSA is not a traditional meningitis pathogen, it commonly causes central nervous system (CNS) infections in association with trauma and neurosurgery (e.g., instrumentation for cerebrospinal fluid shunts). Vancomycin is the preferred treatment for MRSA CNS infections; alternative agents include linezolid or SMX-TMP (Liu et al., 2011Liu C. Bayer A. Cosgrove S.E.

Invasion and Multiplication of Helicobacter pylori in Gastric Epithelial Cells and Implications for Antibiotic Resistance

Helicobacter pylori is a Gram-negative, spiral-shaped bacterium that infects more than 50% of the human population and can cause gastritis, peptic ulcer, or gastric malignancies. It is generally viewed as an extracellular microorganism. In a gentamicin protection assay on AGS or MKN45 cells, H. pylori could invade the epithelial cells and multiply within double-layer vesicles either on the plasma membrane or in the cytoplasm. A 5-fold increase in the number of bacteria was recultured from the infected cells at 12 h, compared with the number of invading cells at 2.5 h postinfection. The autophagic vesicles induced by H. pylori are the sites of replication and also of the degradation of the replicating bacteria after fusion with lysosomes. Many H. pylori bacteria in coccoid form associated with the plasma membrane can be released into culture. Only cell-penetrating antibiotics can enhance the intracellular killing of the replicating bacteria. The multiplication of H. pylori within cells provides a niche for its resistance to antibacterial therapy and has a significant impact on its biological life cycle.

Antibiotic Treatment of Wheezing in Children With Asthma: What Is the Practice?

Antibiotics are not recommended for the treatment of wheezing in children with asthma, but little is known about their use. This study was undertaken to evaluate trends and determinants of antibiotic use in children with wheezing during the fiscal years 1995 through 2001. Using the population-based health care and prescription databases in Manitoba, Canada, this descriptive study examined time trends in antibiotic prescription use for wheezing episodes in a population of children with asthma. The likelihood of receiving an antibiotic prescription according to child and physician characteristics also was determined. Annual population-based rates of antibiotic prescriptions for wheezing episodes were modeled by age and antibiotic class, using general estimating equations. The odds ratio for receiving an antibiotic prescription according to child demographics and physician factors was determined from hierarchical linear modeling. The antibiotic prescription rate for wheezing decreased by 28% from 708 prescriptions per 1000 children with asthma in 1995 to 511 prescriptions in 2001. Fifteen-fold increases in use were observed for broader spectrum macrolides in preschool children. Twenty-three percent of physician visits for wheezing resulted in an immediate antibiotic prescription, but this percentage increased to 64% for antibiotics that were received within 7 days of the episode. General practitioners prescribed antibiotics more often than did pediatricians. Physicians who were not trained in Canada or the United States were 40% more likely to prescribe antibiotics than their counterparts. Antibiotic use for wheezing in children declined in the 1990s, but the increased use of broader spectrum macrolides has implications for antibiotic resistance. A link between antibiotic prescribing and physician specialty and location of training identifies opportunities for intervention.

Decrease in antibiotic use among children in the 1990s: not all antibiotics, not all children.

Decreases in antibiotic use were widely reported in the 1990s. This study was undertaken to determine trends in the use of antibiotics from fiscal year (FY) 1995 (April 1995 to March 1996) to FY 2001 in a complete population of Manitoba children. Using Manitoba's health care databases, we determined annual population-based rates of antibiotic prescription among children by antibiotic class (narrow-spectrum and broader-spectrum antibiotics), age group, physician diagnosis (e.g., otitis media or bronchitis) and neighbourhood income in urban areas (derived from the 1996 census). Antibiotic prescription rates were generated within a generalized linear model framework with general estimating equations, and differences between FY 2001 and FY 1995 were tested. Differences in antibiotic use over time were compared across antibiotic classes, age groups, diagnoses and income neighbourhoods. The overall antibiotic prescription rate decreased by almost one-third, from 1.2 prescriptions per child in FY 1995 to 0.9 prescriptions in FY 2001. Total antibiotic use declined for all respiratory tract infections; decreases were greatest for the sulfonamides (decrease to less than one-third the FY 1995 rate) and narrow-spectrum macrolides (decrease to less than half the FY 1995 rate). In contrast, the FY 2001 rate for broader-spectrum macrolides was as much as 12.5 times the FY 1995 rate. Otitis media accounted for one-quarter of the use of the latter agents. Preschool children and low-income children received the greatest number of antibiotic prescriptions. Declines in antibiotic prescriptions were of a lesser magnitude for low-income children (for whom rates in FY 2001 were four-fifths the rates in FY 1995) than for higher-income children (for whom rates in FY 2001 were about two-thirds the rates in FY 1995). Overall, antibiotic use declined over the late 1990s in this population of Canadian children, but the increasing use of broader-spectrum macrolides and higher rates of antibiotic use among preschool and low-income children may have implications for antibiotic resistance.

Biofilms and Biocides: Are there Implications for Antibiotic Resistance?

Considerable controversy surrounds the use of biocides in an ever increasing range of consumer products and the possibility that their indiscriminate use might reduce biocide effectiveness and alter susceptibilities towards antibiotics. These concerns have been based largely on the isolation of resistant mutants from in vitro monoculture experiments. To date, however the emergence of biocide-resistant strains in-vivo has not been reported and a number of environmental survey studies have failed to associate biocide use with antibiotic resistance. This article gives an overview of the issues as they currently stand and reviews data generated in our laboratory over the last five years where we have used laboratory microcosms of the environment and oral cavity to better understand the possible effects of real-life biocide exposure of these high risk ecosystems. In general, whilst biocide susceptibility changes can be demonstrated in pure culture, especially for E. coli towards triclosan, it has not been possible to reproduce these effects during chronic, sublethal dosing of complex communities. We conclude from this review that whilst the incorporation of antibacterial agents into a widening sphere of personal products may not overtly impact on the patterns of microbial susceptibility observed in the environment, the precautionary principle suggests that the use of biocides should be limited to applications where clear hygienic benefits can be demonstrated.

X-ray structure of an M. jannaschii DNA-binding protein: implications for antibiotic resistance in S. aureus.

X-ray structure of an M. jannaschii DNA-binding protein: implications for antibiotic resistance in S. aureus.

Mechanisms and Clinical Implications of Antibiotic Resistance in Bacteria

Mechanisms and Clinical Implications of Antibiotic Resistance in Bacteria