In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents.     

Validation of a Novel Murine Wound Model of Acinetobacter baumannii Infection

Patients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which include A. baumannii (the ESKAPE pathogens are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). As new therapies are being developed to counter A. baumannii infections, animal models are also needed to evaluate potential treatments. Here, we present an excisional, murine wound model in which a diminutive inoculum of a clinically relevant, multidrug-resistant A. baumannii isolate can proliferate, form biofilms, and be effectively treated with antibiotics. The model requires a temporary, cyclophosphamide-induced neutropenia to establish an infection that can persist. A 6-mm-diameter, full-thickness wound was created in the skin overlying the thoracic spine, and after the wound bed was inoculated, it was covered with a dressing for 7 days. Uninoculated control wounds healed within 13 days, whereas infected, placebo-treated wounds remained unclosed beyond 21 days. Treated and untreated wounds were assessed with multiple quantitative and qualitative techniques that included gross pathology, weight loss and recovery, wound closure, bacterial burden, 16S rRNA community profiling, histopathology, peptide nucleic acid-fluorescence in situ hybridization, and scanning electron microscopy assessment of biofilms. The range of differences that we are able to identify with these measures in antibiotic- versus placebo-treated animals provides a clear window within which novel antimicrobial therapies can be assessed. The model can be used to evaluate antimicrobials for their ability to reduce specific pathogen loads in wounded tissues and clear biofilms. Ultimately, the mouse model approach allows for highly powered studies and serves as an initial multifaceted in vivo assessment prior to testing in larger animals.     

Next Science Wound Gel Technology,a Novel Agent That Inhibits Biofilm Development by Gram-Positive and Gram-Negative Wound Pathogens

Loss of the skin barrier facilitates the colonization of underlying tissues with various bacteria, where they form biofilms that protect them from antibiotics and host responses. Such wounds then become chronically infected. Topical antimicrobials are a major component of chronic wound therapy, yet currently available topical antimicrobials vary in their effectiveness on biofilm-forming pathogens. In this study, we evaluated the efficacy of Next Science wound gel technology (NxtSc), a novel topical agent designed to kill planktonic bacteria, penetrate biofilms, and kill the bacteria within. In vitro quantitative analysis, using strains isolated from wounds, showed that NxtSc inhibited biofilm development by Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae by inhibiting bacterial growth. The gel formulation NxtSc-G5, when applied to biofilms preformed by these pathogens, reduced the numbers of bacteria present by 7 to 8 log₁₀ CFU/disc or CFU/g. In vivo, NxtSc-G5 prevented biofilm formation for 72 h when applied at the time of wounding and infection and eliminated biofilm infection when applied 24 h after wounding and infection. Storage of NxtSc-G5 at room temperature for 9 months did not diminish its efficacy. These results establish that NxtSc is efficacious in vitro and in vivo in preventing infection and biofilm development by different wound pathogens when applied immediately and in eliminating biofilm infection already established by these pathogens. This novel antimicrobial agent, which is nontoxic and has a usefully long shelf life, shows promise as an effective agent for the prevention and treatment of biofilm-related infections.     

A comparison of the prophylactic uses of topical mupirocin and nitrofurazone in murine crush contaminated wounds

Objectives

This work was conducted to study the prophylactic efficacy of 2 topical antibiotic ointments (mupirocin and nitrofurazone) against wound infection in experimental contaminated crush wounds.

Methods

Male Wistar rats underwent two 2-cm incisions at the back side and randomized into 3 groups—placebo (n = 14), mupirocin (n = 14), and nitrofurazone (n = 14)—and infected with either Staphylococcus aureus or S pyogenes. All wound edges were crushed for 5 seconds with hemostats to simulate crush injury before inoculation of the microorganisms. Half of the wounds were sutured and the other half left open. These wounds were treated 3 times daily for 6 days with topical mupirocin, nitrofurazone, or petrolatum (as placebo). At the end of 6 days, excisional biopsies were taken from wound edges and histopathologic assessments were made based on neutrophilic infiltration, edema formation, myofibroblastic proliferation, and granulation tissue formation. For the microbiologic assessments, quantitative tissue cultures were made.

Results

In S aureus-inoculated wounds, mupirocin showed higher antibacterial activity against bacterial colonization and reduced infection rates compared to placebo groups. The same effect was observed for the infection rates in S pyogenes-inoculated wounds. In S pyogenes-inoculated open wounds, nitrofurazone showed higher antibacterial activity against infection, but this effect was not observed in closed wounds. In S pyogenes- and S aureus-infected wounds, mupirocin treatment significantly lowered infection rates compared to nitrofurazone treatment. Histopathologic examination showed higher myofibroblastic proliferation and higher volume of granulation tissue in the nitrofurazon groups compared to the mupirocin groups.

Conclusion

Topical mupirocin application was effective against crush wound infections inoculated with S pyogenes and S aureus. Nitrofurazone provides better granulation tissue formation, but did not effectively prevent bacterial colonization and infection in crush contaminated wounds.     

Treatment of skin and soft tissue infections in the elderly: A review

Background: Skin and soft tissue infections (SSTIs) have become the second most common type of infection among persons residing in long-term care facilities.Objective: The purpose of this article was to review the latest information on SSTIs among the elderly, including age-related changes, challenges, and treatment strategies in the era of emerging bacterial resistance.Methods: Relevant information was identified through a search of MEDLINE (1970—April 2010), International Pharmaceutical Abstracts (1970—April 2010), and Google Scholar using the terms skin and soft tissue infection, skin and skin structure infection, cellulitis, treatment guidelines, and elderly. Additional publications were found by searching the reference lists of the identified articles. Trials published since 1970 were selected for this review if they prospectively evaluated mostly adults (≥18 years of age), included >50 patients, and reported diagnostic criteria as well as clinical outcomes in patients treated for simple or complicated SSTIs.Results: Fifty-eight of 664 identified studies were selected and included in this review. A search of the literature did not identify any prospective clinical trials that were conducted exclusively in the elderly. Information on the treatment of SSTIs in the elderly was based solely on clinical studies that were conducted in adults in general. As recommended by the Infectious Diseases Society of America (IDSA) 2008 update, SSTIs should be suspected in elderly patients who have skin lesions and present with a decline in functional status, with or without fever. Patients who present with symptoms of systemic toxicity should be hospitalized for further evaluation. Current challenges in the management of SSTIs include the rapid emergence of community-acquired, methicillin-resistant Staphylococcus aureus (CA—MRSA), the emergence of macrolide-resistant streptococci within the past decade, and the lack of a reliable algorithm to differentiate potentially life-threatening SSTIs that require aggressive interventions and prompt hospitalization from those that can be managed in an outpatient setting. S aureus was the most common cause of SSTIs, being isolated in 42.8% (5015/11,723) of wounds, followed by streptococci. Common SSTIs in the elderly such as shingles, diabetic foot infections, infected pressure ulcers, and scabies, and their treatment were also discussed. Based on reviews of published trials, treatment of simple SSTIs generally consisted of administration of agents with activity against S aureus and Streptococcus species such as a penicillinase-resistant β-lactam, a first-generation cephalosporin, or clindamycin. Broadening of the antimicrobial spectrum to include gram-negative and anaerobic organisms should be implemented for complicated SSTIs such as diabetic foot infections and infected pressure ulcers. Local rates of MRSA, CA—MRSA, and macrolide-resistant streptococci should be considered when selecting empiric therapy.Conclusions: A search of the literature did not identify any prospective clinical trials on the treatment of SSTIs in the elderly; therefore, it is recommended to follow treatment based on the current IDSA guidelines. More research and publications are needed to establish proper selection of antimicrobial agents, treatment strategies, and duration of therapy of SSTIs in the elderly population.     

Responsiveness of Experimental Surgical-Wound Infections to Topical Chemotherapy

Topical agents freshly formulated in a cream base vehicle as well as commercial topical preparations were used to evaluate in mice the responsiveness of experimental surgical wounds infected with Staphylococcus aureus or Pseudomonas aeruginosa to chemotherapy. The responsiveness of the infections to therapy or the efficacy of a topical agent was assessed primarily by means of wound counts of the infecting organism before and after the employment of an immediate (prophylactic) or delayed (therapeutic) treatment regimen. From tests of several concentrations of an agent formulated in the vehicle, a median effective dose could be determined. In the case of the lethal P. aeruginosa infection, a median protective dose could be determined. Both infections were found to be quite susceptible to treatment with those topical agents that demonstrated good activity in vitro against the test organisms. The results of the investigation indicated that the model infections were suitable for the screening of potential topical agents in vivo.     

Low or High Doses of Cefquinome Targeting Low or High Bacterial Inocula Cure Klebsiella pneumoniae Lung Infections but Differentially Impact the Levels of Antibiotic Resistance in Fecal Flora

The combination of efficacious treatment against bacterial infections and mitigation of antibiotic resistance amplification in gut microbiota is a major challenge for antimicrobial therapy in food-producing animals. In rats, we evaluated the impact of cefquinome, a fourth-generation cephalosporin, on both Klebsiella pneumoniae lung infection and intestinal flora harboring CTX-M-producing Enterobacteriaceae. Germfree rats received a fecal flora specimen from specific-pathogen-free pigs, to which a CTX-M-producing Escherichia coli strain had been added. K. pneumoniae cells were inoculated in the lungs of these gnotobiotic rats by using either a low (10⁵ CFU) or a high (10⁹ CFU) inoculum. Without treatment, all animals infected with the low or high K. pneumoniae inoculum developed pneumonia and died before 120 h postchallenge. In the treated groups, the low-inoculum rats received a 4-day treatment of 5 mg/kg of body weight cefquinome beginning at 24 h postchallenge (prepatent phase of the disease), and the high-inoculum rats received a 4-day treatment of 50 mg/kg cefquinome beginning when the animals expressed clinical signs of infection (patent phase of the disease). The dose of 50 mg/kg targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae. A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae. These findings might have implications for the development of new antimicrobial treatment strategies that ensure a cure for bacterial infections while avoiding the amplification of resistance genes of human concern in the gut microbiota of food-producing animals.     

Development and Validation of an In Vitro Pharmacokinetic/Pharmacodynamic Model To Test the Antibacterial Efficacy of Antibiotic Polymer Conjugates

This study describes the use of a novel, two-compartment, static dialysis bag model to study the release, diffusion, and antibacterial activity of a novel, bioresponsive dextrin-colistin polymer conjugate against multidrug resistant (MDR) wild-type Acinetobacter baumannii. In this model, colistin sulfate, at its MIC, produced a rapid and extensive drop in viable bacterial counts (<2 log₁₀ CFU/ml at 4 h); however, a marked recovery was observed thereafter, with regrowth equivalent to that of control by 48 h. In contrast, dextrin-colistin conjugate, at its MIC, suppressed bacterial growth for up to 48 h, with 3 log₁₀ CFU/ml lower bacterial counts after 48 h than those of controls. Doubling the concentration of dextrin-colistin conjugate (to 2× MIC) led to an initial bacterial killing of 3 log₁₀ CFU/ml at 8 h, with a similar regrowth profile to 1× MIC treatment thereafter. The addition of colistin sulfate (1× MIC) to dextrin-colistin conjugate (1× MIC) resulted in undetectable bacterial counts after 4 h, followed by suppressed bacterial growth (3.5 log₁₀ CFU/ml lower than that of control at 48 h). Incubation of dextrin-colistin conjugates with infected wound exudate from a series of burn patients (n = 6) revealed an increasing concentration of unmasked colistin in the outer compartment (OC) over time (up to 86.3% of the initial dose at 48 h), confirming that colistin would be liberated from the conjugate by endogenous α-amylase within the wound environment. These studies confirm the utility of this model system to simulate the pharmacokinetics of colistin formation in humans administered dextrin-colistin conjugates and further supports the development of antibiotic polymer conjugates in the treatment of MDR infections.     

Cutaneous Methicillin-Resistant Staphylococcus aureus in a Suburban Community Hospital Pediatric Emergency Department

Background: Studies on methicillin-resistant Staphylococcus aureus (MRSA) infections have typically focused on pediatric and adult populations at urban tertiary care hospitals. Limited data exist on MRSA rates in skin and soft tissue infections (SSTI) in suburban community hospital pediatric emergency departments (PED). Objectives: To describe the prevalence of MRSA in SSTIs in a contemporary suburban community hospital PED population. Methods: Patients 0-21 years old with SSTI wound cultures who were seen at our PED from 2003-2007 were studied. Data analyzed included type of infection (abscess vs. non-abscess), site of infection, and culture results. Chi-squared and t-tests were used as appropriate;p < 0.05 was considered significant. Results: During the study period, 204 cultures were obtained for SSTIs, 11 of which were contaminants. The subjects had a mean age of 12.9 years (SD 6.8 years); 60% were male. The prevalence of MRSA was 27%; MRSA was present in 30% of abscesses vs. 2.2% of non-abscess SSTI (p < 0.005). By year, the prevalence of MRSA was 10% in 2003, 31% in 2004, 33% in 2005, 31% in 2006, and 29% in 2007. No differences between MRSA and non-MRSA infections were present for gender, age, or site of infection. Conclusions: At our suburban community hospital pediatric ED, MRSA was present in 30% of all SSTI wound cultures; MRSA was unlikely with non-abscess SSTI. Our overall MRSA prevalence data among SSTIs are consistent with previously published reports in pediatric ED populations but may be less than those reported in the adult literature.     

Aerobic and anaerobic microbiology of infection after trauma

Clinical and laboratory data from 1973 to 1988 were retrospectively reviewed to study the microbiology of infection following trauma. A total of 368 specimens obtained from 340 trauma patients showed bacterial growth. The traumas included lacerations (163), blunt trauma (76), penetrating trauma (65), bites (20), and open fractures (10). Anaerobic bacteria only were isolated in 119 (32%) specimens, aerobic bacteria only in 58 (16%), and mixed aerobic-anaerobic flora in 191 (52%). A total of 444 anaerobic (1.2 isolates per specimen) and 267 aerobic or facultative (0.7 per specimen) were recovered. The predominant anaerobic bacteria included Bacteroides fragilis group (119 isolates), Peptostreptococcus spp (113), Clostridium spp (78), Prevotella spp (58), and Fusobacterium spp (23). The predominant aerobic bacteria included Escherichia coli (83), Staphylococcus aureus (61), Streptococcus pyogenes (27), Streptococcus group D (16), and Klebsiella pneumoniae (16). The types of infections included abscesses (109), bacteremia (32), bites (13), empyema (10), osteomyelitis (21), peritonitis (52), thrombophlebitis (12), and wounds (116, including posttraumatic wounds, cellulitis, stump wound, decubitus ulcers, myositis, and fasciitis). S aureus was isolated at all sites. However, organisms of the oropharyngeal flora predominated in infections that originated from that location (ie, head and neck wounds, and abscesses or bites), and those of the gastrointestinal flora predominated in infections that originated from that site (ie, peritonitis, abdominal abscesses, decubitus ulcers). This study showed the polymicrobial nature of many infections that follow trauma.     

UVC light prophylaxis for cutaneous wound infections in mice

UVC light has long been known to be highly germicidal but has not been much developed as a therapy for infections. This study investigated the potential of UVC light for the prophylaxis of infections developing in highly contaminated superficial cutaneous wounds. In vitro studies demonstrated that the pathogenic bacteria Pseudomonas aeruginosa and Staphylococcus aureus were inactivated at UVC light exposures much lower than those needed for a similar effect on mammalian keratinocytes. Mouse models of partial-thickness skin abrasions infected with bioluminescent P. aeruginosa and S. aureus were developed. Approximately 10(7) bacterial cells were inoculated onto wounds measuring 1.2 by 1.2 cm on the dorsal surfaces of mice. UVC light was delivered at 30 min after bacterial inoculation. It was found that for both bacterial infections, UVC light at a single radiant exposure of 2.59 J/cm(2) reduced the bacterial burden in the infected mouse wounds by approximately 10-fold in comparison to those in untreated mouse wounds (P < 0.00001). Furthermore, UVC light increased the survival rate of mice infected with P. aeruginosa by 58.3% (P = 0.0023) and increased the wound healing rate in mice infected with S. aureus by 31.2% (P < 0.00001). DNA lesions were observed in the UVC light-treated mouse wounds; however, the lesions were extensively repaired by 48 h after UVC light exposure. These results suggested that UVC light may be used for the prophylaxis of cutaneous wound infections.     

Activity of Imipenem against Klebsiella pneumoniae Biofilms In Vitro and In Vivo

Encapsulated Klebsiella pneumoniae has emerged as one of the most clinically relevant and more frequently encountered opportunistic pathogens in combat wounds as the result of nosocomial infection. In this report, we show that imipenem displayed potent activity against established K. pneumoniae biofilms under both static and flow conditions in vitro. Using a rabbit ear model, we also demonstrated that imipenem was highly effective against preformed K. pneumoniae biofilms in wounds.     

Characterization and Quantitation of Experimental Surgical-Wound Infections Used to Evaluate Topical Antibacterial Agents

Reproducible experimental surgical-wound infections in mice for use in the evaluation of topical antibacterial agents are described. The experimental would was created on the backs of mice by means of a midline incision and was infected by means of cotton sutures monocontaminated with Staphylococcus aureus or Pseudomonas aeruginosa. The course of these wound infections was followed by quantitation of surface bacteria through use of a surface rinse technique. Surface wound counts of the infecting organisms thus obtained appeared to reflect the dynamics of the total wound count, as determined by homogenization of biopsied tissue. Treatment of infected wounds with a placebo cream had only a slight effect on surface wound counts and on mortality in the case of the S. aureus infection but enhanced markedly the lethality of the P. aeruginosa infection.     

Emergence of Resistant Klebsiella pneumoniae in the Intestinal Tract during Successful Treatment of Klebsiella pneumoniae Lung Infection in Rats

Antibiotic treatment of lung infections may lead to the emergence of resistance in the gut flora. Appropriate dosing regimens could mitigate this adverse effect. In gnotobiotic rats harboring intestinal Escherichia coli and Enterococcus faecium populations, a lung infection by Klebsiella pneumoniae was instigated with two different sizes of inoculum to represent an early or a late initiation of antibiotic treatment. The rats were treated with marbofloxacin, an expanded-spectrum fluoroquinolone, by a single-shot administration or a fractionated regimen over 4 days. Intestinal bacterial populations were monitored during and after treatment. At the infection site, bacterial cure without any selection of resistance was observed. Whatever the dosage regimen, fluoroquinolone treatment had a transient negative impact on the E. coli gut population but not on that of E. faecium. The intestinal flora was colonized by the pathogenic lung bacteria, and there was the emergence of intestine-resistant K. pneumoniae, occurring more often in animals treated with a single marbofloxacin dose than with the fractionated dose. Bacterial cure without resistance selection at the infection site with fluoroquinolone treatment can be linked to colonization of the digestive tract by targeted pulmonary bacteria, followed by the emergence of resistance.The emergence of antimicrobial resistance during antibiotic treatment can occur in the infected organ system and/or in the endogenous normal gut flora (3). Antimicrobial agents, including fluoroquinolones, can be extensively excreted into the intestinal tract, exposing the normal host flora to antimicrobial selective pressure (i.e., inhibition of competing microflora). This may lead to a secondary development of antibiotic-resistant gut organisms (2, 3, 17). Klebsiella pneumoniae is an important opportunistic pathogen implicated in nosocomial bacterial infections (19). Epidemiological studies have shown that the majority of K. pneumoniae infections are often preceded by colonization of the patient''s gastrointestinal tract by the bacteria (9, 10). Recent reports suggest that fluoroquinolone-resistant Klebsiella pneumoniae isolates are common in many long-term care facilities and hospitals and are often associated with multidrug-resistant phenotypes (11, 22). The origins of this resistant K. pneumoniae gut subpopulation deserve attention. A possible factor contributing to the emergence of a resistant subpopulation of K. pneumoniae in the gut could be inadequate treatment of a prior K. pneumoniae infection, with secondary gut colonization by K. pneumoniae. This K. pneumoniae strain may then expand in the gut flora due to the selective pressure of the antibiotic reaching the gut lumen. Factors such as the concentration of the antimicrobial in the intestinal tract, the duration of the antimicrobial therapy, and the associated degree of disruption of the microflora may influence the likelihood that K. pneumoniae-resistant strains will or will not emerge at the gut level (3, 21). In previous studies on rodent models of Escherichia coli thigh infection and K. pneumoniae lung infection, we showed that the bacterial load at the start of antimicrobial treatment plays an important role in the enrichment of resistant strains at the infection site (4, 8). With a low inoculum, an early start of antimicrobial treatment with marbofloxacin, an expanded-spectrum fluoroquinolone extensively used in veterinary medicine, prevented mutant enrichment at the infection site, whereas a late start of the antimicrobial treatment with a high inoculum led to the enrichment of the resistant mutant subpopulation. Moreover, we showed that the emergence of resistance was dependent on the total marbofloxacin dose and dosage regimen.The aim of the present study was to assess, in a K. pneumoniae experimental infection model, the impact of different marbofloxacin dosage regimens on the commensal intestinal flora and to test the hypothesis that the critical site of emergence of resistance of a targeted lung pathogen during antibiotic treatment may be not the lung itself but the gut flora. With this as our aim, we developed a model of lung infection in gnotobiotic rats, with two inoculum sizes of K. pneumoniae, each treated with two different marbofloxacin dosage regimens. We chose to work with a gnotobiotic model harboring a Gram-positive and a Gram-negative bacterial population in the intestine.     

Activity of omadacycline tested against Streptococcus pneumoniae from a global surveillance program (2014)

The activity of omadacycline and comparators when tested against a subset of Streptococcus pneumoniae from US and European regions of a 2014 global surveillance program (304 isolates) are reported. These MIC results were compared to those obtained when testing S. pneumoniae from 2010 surveillance (1,834 isolates). The omadacycline MIC_50/90 for S. pneumoniae (2014) was 0.06/0.06 μg/mL, similar to 2010 (MIC_50/90, 0.06/0.12 μg/mL). The omadacycline MIC₉₀ (0.06–0.12 μg/mL) was similar for the penicillin-susceptible, -intermediate, -resistant, multidrug-resistance (MDR; ≥3 classes), and ceftriaxone nonsusceptible subgroups. Omadacycline MIC₉₀ values were 0.06–0.12 μg/mL for S. pneumoniae from the US and Europe. There was a high degree of resistance with doxycycline, erythromycin and trimethoprim-sulfamethoxazole in both US and EU. For penicillin-resistant S. pneumoniae, resistance to doxycycline and tetracycline in US/Europe was 64.2/61.0% and 63.8/60.5%, respectively, erythromycin 91.2/75.1, and ceftriaxone 7.3/4.0%. The potent activity of omadacycline against S. pneumoniae indicates that omadacycline merits further study in bacterial pneumonia, especially where MDR may be a concern.     

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of the Japanese Society of Chemotherapy,the Japanese Association for Infectious Diseases,and the Japanese Society for Clinical Microbiology in 2019–2020: General view of the pathogens' antibacterial susceptibility

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute.Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were β-lactamase-producing ampicillin resistant and β-lactamase-negative ampicillin resistant, respectively. Extended-spectrum β-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-β-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents.     

High prevalence of multiresistance in levofloxacin-nonsusceptible Streptococcus pneumoniae isolates in Korea

Korea exhibits the highest rates of multidrug resistance among Streptococcus pneumoniae. The increasing use of levofloxacin has raised concern about the dissemination of levofloxacin resistance in dominant multidrug-resistant (MDR) clones of our pneumococcal population. A total of 50 levofloxacin-nonsusceptible S. pneumoniae (MIC, ≥4 μg/mL) collected from a multihospital network from 1996 to 2006 were analyzed for serotype, antibiotic resistance profile, quinolone resistance–determining region mutation, and multilocus sequence type. Most levofloxacin-nonsusceptible S. pneumoniae (94.0%) exhibited an MDR phenotype. This phenotype was closely associated with a limited number of epidemic MDR clones that are well-known key agents of the global spread of antimicrobial resistance in S. pneumoniae. However, the clonal dissemination of levofloxacin-nonsusceptible S. pneumoniae was rare. Levofloxacin-nonsusceptible clones with nonvaccine serotypes increased during the post-vaccine era in this study. This result suggests that Korean clinicians must be aware of the levofloxacin resistance trend and need to be more prudent for the first choice of fluoroquinolone for empiric treatment of respiratory tract infections in clinical setting. Moreover, the emergence of new clones and their variations may be more frequently associated with resistance under this selective pressure, such as the introduction of a 7-valent pneumococcal conjugate vaccine into our community.