Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.

Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter.

Retrospective study of the efficacy of vascularized tissue transfer for treating antibiotic-resistant bacteria-infected wound: Comparison with clean and antibiotic-sensitive bacteria-infected wound.

ABSTRACT: If wounds are infected with bacteria resistant to an empirical antibiotic regimen, effective wound treatment will be delayed. This can delay wound healing and lengthen hospital stays, increasing the costs to patients. Long-term antibiotic use can also result in minor and major complications, such as diarrhea, antibiotic resistance, or life-threatening leukopenia. Multidrug-resistant (MDR) bacteria make wound treatment even more difficult. Traditionally, surgeons thought that adequate infection control should be established before soft tissue coverage. However, wounds infected by MDR do not heal well with this traditional method and there are no optimal treatment guidelines for MDR bacteria-contaminated wounds.We reviewed 203 patients who underwent vascularized flap surgery from 2012 to 2019 to cover wounds. Class IV and I wounds were compared according to the Centers for Disease Control and Prevention classification. Class IV was further classified as antibiotic-resistant (ARB) and antibiotic-sensitive (ASB) bacteria. Wound size, mode, location, pathogens, healing time, and basic demographics were evaluated. Data were compared using Cramer's V and one-way ANOVA or independent t tests.The average healing time was longer in the ARB (19.7 [range 7-44] days) and ASB (17.9 [range 2-36] days) groups than in the Clean group (16.5 [range 7-28] days). Healing time differed in the 3 groups (P = .036). It was longer in the class IV group than in the class I group (P = .01). However, it was not statistically different between the ARB and ASB groups (P = .164).In our study the difference in healing time was small when vascularized tissue transfer was done in ARB-infected wound compared with ASB-infected and clean wound. It is necessary to perform surgery using vascularized tissue for the infected wound of antibiotic-resistant bacteria.

Needs assessment for novel Gram-negative antibiotics in US hospitals: a retrospective cohort study.

BACKGROUND: Evidence-based needs assessments for novel antibiotics against highly-resistant Gram-negative infections (GNIs) are scarce. We aimed to use real-world data from an electronic health record repository to identify treatment opportunities in US hospitals for GNIs resistant to all first-line drugs. METHODS: For this retrospective cohort study, population estimates with an unmet need for novel Gram-negative antibiotics were quantified using the Cerner Health Facts database (2009-15), aggregating episodes of infection in US hospitals with pathogens displaying difficult-to-treat resistance (DTR; resistance to carbapenems, other ß-lactams, and fluoroquinolones) and episodes involving empirical coverage with reserve drugs (colistin or polymyxin B and aminoglycosides). Episodes displaying extended-spectrum cephalosporin resistance (ECR) were also estimated. Episodes were multiplied by site-specific and fixed 14-day treatment durations for conservative and liberal days-of-therapy (DOT) estimates and stratified by site and taxon. Hospital type-specific DOT rates were reliability adjusted to account for random variation; cluster analyses quantified contribution from outbreaks. FINDINGS: Across 2 996 271 inpatient encounters and 134 hospitals, there were 1352 DTR-GNI episodes, 1765 episodes involving empirical therapy with colistin or polymyxin B, and 16 632 episodes involving aminoglycosides. Collectively, these yielded 39·0 (conservative estimate) to 138·2 (liberal estimate) DOT per 10 000 encounters for a novel DTR-GNI-targeted drug, whereas greater treatment opportunities were identified for ECR (six times greater) and ß-lactam susceptible GNIs (70 times greater). The most common DTR-GNI site and pathogen was lower respiratory (14·3 [43·3%] of 33 DOT per 10 000 encounters) and Pseudomonas aeruginosa (522 [38·1%] of 1371 episodes), whereas Enterobacteriaceae urinary-tract infections dominated the ECR or carbapenem-sparing niche (59·0% [5589 of 9535 episodes]) equating to 210·7 DOT per 10 000 encounters. DTR Stenotrophomonas maltophilia, Burkholderia spp, and Achromobacter spp represented less than 1 DOT per 10 000 encounters each. The estimated need for DTR-GNI-targeted antibiotics saw minor contributions by outbreaks and varied from 0·5 to 73·1 DOT per 10 000 encounters by hospital type. INTERPRETATION: Suspected or documented GNIs with no or suboptimal treatment options are relatively infrequent. Non-revenue-based strategies and innovative trial designs are probably essential to the development of antibiotics with improved effectiveness for these GNIs. FUNDING: Center for Drug Evaluation and Research, US Food and Drug Administration; Intramural Research Program, National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases and the National Cancer Institute.

[Antibiotic strategy in pleural empyema in children: Consensus by the DELPHI method]. / Stratégie antibiotique dans les pleurésies en pédiatrie : consensus par méthode DELPHI.

INTRODUCTION: The evolution of the microbial epidemiology of pleuropulmonary infections complicating community-acquired pneumonia has resulted in a change in empirical or targeted antibiotic therapy in children in the post Prevenar 13 era. The three main pathogens involved in pleural empyema in children are Streptococcus pneumoniae, Staphylococcus aureus and group A Streptococcus. METHODS: A questionnaire according to the DELPHI method was sent to experts in the field (paediatric pulmonologists and infectious disease specialists) in France with the purpose of reaching a consensus on the conservative antibiotic treatment of pleural empyema in children. Two rounds were completed as part of this DELPHI process. RESULTS: Our work has shown that in the absence of clinical signs of severity, the prescription of an intravenous monotherapy is consensual but there is no agreement on the choice of drug to use. A consensus was also reached on treatment adjustment based on the results of blood cultures, the non-systematic use of a combination therapy, the need for continued oral therapy and the lack of impact of pleural drainage on infection control. On the other hand, after the second round of DELPHI, there was no consensus on the duration of intravenous antibiotic therapy and on the treatment of severe pleural empyema, especially when caused by Staphylococci. CONCLUSIONS: The result of this work highlights the needed for new French recommendations based on the evolution of microbial epidemiology in the post PCV13 era.

Prevalence of E. Coli in Urinary Tract Infection of Children Aged 1-15 Years in A Medical College of Eastern Nepal.

INTRODUCTION: Urinary tract infection is one of the commonest causes of childhood morbidity. Early diagnosis and appropriate choice of antimicrobials is essential. Hence, this study aims to identify the prevalence of Escherichia coli in childhood urinary tract infections. METHODS: This was a hospital based descriptive cross-sectional study conducted in Nobel Medical College, Biratnagar over a period of one year. A total of 163 cases aged 1-15 years were included and clinical profile, laboratory reports including bacterial isolates in urine cultures and their sensitivity patterns were documented. RESULTS: The prevalence of Escherichia coli is 45 (53.57%) C.I. Escherichia coli was the most common organism isolated in bacterial cultures followed by Klebsiella 12 (14.29%), Enterococcus 10 (11.90%). Urinary tract infection was common among females with male: female ratio of 1:2.3. Fever 152 (93.2%) and abdominal pain 113 (69.3%) were the most common presenting symptoms. Escherichia coli was found most sensitive to Nitrofurantoin 43 (95.5%) followed by Ciprofloxacin 41 (91.1%) and Amikacin 40 (88.8%). CONCLUSIONS: Urinary tract infections in childhood require prompt attention and treatment to prevent significant morbidity and mortality. From this study it can be concluded that Escherichia coli is one of the most common isolates in urine culture and Aminoglycosides and Fluoroquinolones can be accepted as empirical treatment regimens for childhood Urinary tract infections.

Activity of Potential Alternative Treatment Agents for Stenotrophomonas maltophilia Isolates Nonsusceptible to Levofloxacin and/or Trimethoprim-Sulfamethoxazole.

Stenotrophomonas maltophilia is difficult to treat due to the production of multiple intrinsic and acquired mechanisms of resistance. Trimethoprim-sulfamethoxazole (TMP-SMZ) and the fluoroquinolones have traditionally been considered the drugs of choice but are plagued by increasing resistance and adverse drug effects. The objective of this study was to evaluate the in vitro activities of 12 clinically relevant antimicrobials against clinical S. maltophilia isolates nonsusceptible to levofloxacin and/or TMP-SMZ. A diverse panel of 41 clinical S. maltophilia isolates collected through the SENTRY Antimicrobial Surveillance Program from 2008 to 2018 was evaluated against ceftazidime, ceftazidime-avibactam, chloramphenicol, delafloxacin, levofloxacin, moxifloxacin, eravacycline, minocycline, omadacycline, polymyxin B, and tigecycline. MICs were determined in triplicate via reference broth microdilution and interpreted according to CLSI guidelines where available. MIC distributions and susceptibilities were also compared across infection type, acquisition setting, and geographic origin. Susceptibilities to levofloxacin and TMP-SMZ were 29.3% and 36.6%, respectively. Minocycline displayed the highest susceptibility rate overall (92.7%) and the lowest MIC90 value (4 mg/liter) of any of the 12 agents tested. Only 3 isolates were resistant to levofloxacin, TMP-SMZ, and minocycline. Polymyxin B and tigecycline were the second most active agents. No significant differences were observed in MIC distributions across the 3 strata evaluated. These data demonstrate that few antimicrobials, old or new, maintain reliable activity against resistant S. maltophilia The role of minocycline in the treatment of infections due to S. maltophilia warrants further clinical investigation given its potent in vitro activity and favorable adverse effect profile.

The clinical rate of antibiotic change following empiric treatment for suspected urinary tract infections.

PURPOSE: To determine the rate of antibiotic change in an outpatient setting following empiric treatment of culture proven UTI and to identify risk factors associated with change. METHODS: Patients with suspected UTI and urine culture were reviewed (January 2016-June 2016). Those with a positive culture were categorized by whether or not they were treated empirically. Empiric treatment was evaluated for associations with clinical-demographic data, symptoms and urinalysis (UA). Antibiotic change was evaluated with clinical-demographic data, urine culture, and resistance patterns. RESULTS: 916 urine cultures (636 patients) were included. 391 (43%) cultures were positive, and 164 (42%) were treated empirically. Clinical-demographic data did not differ between groups. Those treated empirically had more documented UTI symptoms (93 vs 58%, P < 0.001), and UA abnormalities including positive nitrites (51 vs 29%, P < 0.001), 3 + leukocyte esterase (27 vs 19%, P = 0.002) and 3 + blood (13 vs 4%, P = 0.005). Of those treated empirically, 42/164 (26%) required an antibiotic change, and this was associated with immunosuppression (12 vs 2%, P = 0.027) resistance to > 3 antibiotics (33 vs 20%, P = 0.039) and also resistance to fluoroquinolone (50 vs 30%, P = 0.016), monobactam (19 vs 7% P = 0.042) and TMP-SMX (52 vs 19%, P < 0.001). CONCLUSIONS: Almost one-quarter of patients treated empirically required antibiotic change. This was driven largely by bacterial resistance. New technologies allowing rapid bacterial identification and sensitivity may improve patient care.

Antimicrobial resistance in cystic fibrosis: A Delphi approach to defining best practices.

BACKGROUND: Antimicrobial susceptibility testing (AST) is a cornerstone of infection management in cystic fibrosis. However, there is little evidence that AST predicts the clinical outcome of CF antimicrobial treatment. It has been suggested there is a need for careful consideration of current AST use by the CF community. METHODS: We engaged a group of experts consisting of pulmonary (adult and pediatric) and infectious disease clinicians, microbiologists, and pharmacists representing a broad international experience. We conducted an iterative systematic survey (Delphi) to determine and quantify consensus regarding key questions facing CF clinicians in the use of respiratory culture results including what tests to order, when to obtain them, and how to act upon the results of the testing. RESULTS: Consensus was reached for many questions but there was not universal agreement to the questions that were addressed. There were some differences with respect to cultures obtained for surveillance compared to when there is clinical worsening. Areas of general consensus include when and how respiratory cultures should be performed, what information should be reported, and when AST should be performed. A key finding is that clinical response to treatment is used to guide treatment decisions rather than AST results. CONCLUSIONS: Recommendations are presented regarding questions related to microbiology testing for patients with CF. We have also offered recommendations for priority research questions.

Clinical characteristics and outcomes of patients with Escherichia coli in airway samples.

PURPOSES: Escherichia coli is one of the most common pathogens in nosocomial and community-acquired infections, but is an uncommon respiratory pathogen. However, this pathogen may at times be seen in respiratory secretions. The study aims to determine the clinical and prognostic value of E. coli in respiratory secretions. METHODS: Cultures of respiratory secretions from hospitalized and outpatients between 2009 and 2016 were screened for isolation of E. coli. We defined three groups of patients: "Sensitive (S)"-growth of E. coli sensitive to all antimicrobials tested; Intermediate (I)-resistant to 1-2 antimicrobial classes; and "Resistant (R)"-resistant to at least three antibiotic classes. We compared factors associated with resistant strains and outcomes between the groups. RESULTS: Eighty patients with E. coli isolates from respiratory secretions were identified while screening 177 712 (4.5: 10 000 samples). Of the E. Coli-positive cultures, 11 were from ambulatory patients, 31 patients were hospitalized and 37 were hospitalized and intubated. Ten people had bronchiectasis and 29 had COPD. Patients with resistant E. coli had significantly more hospitalization days prior to positive culture (S = 1.2 ± 1.89 days, I = 1.23 ± 1.5 days and R = 3.7 ± 5.4 days, respectively; P = 0.002). Mortality was higher in patients with a resistant strain (R) versus (I) or (S) (76.7%, 31.8% and 26.7%, respectively; P < 0.0001) and remained significantly elevated after correction for prior hospital days. CONCLUSIONS: Pulmonary infection due to E. coli is uncommon. Isolation of resistant E. coli is associated with length of previous hospitalization, elevated mortality and may be viewed as a nosocomial pathogen.

In vitro antimicrobial combination testing of and evolution of resistance to the first-in-class spiropyrimidinetrione zoliflodacin combined with six therapeutically relevant antimicrobials for Neisseria gonorrhoeae.

OBJECTIVES: Resistance in Neisseria gonorrhoeae to all gonorrhoea therapeutic antimicrobials has emerged. Novel therapeutic antimicrobials are imperative and the first-in-class spiropyrimidinetrione zoliflodacin appears promising. Zoliflodacin could be introduced in dual antimicrobial therapies to prevent the emergence and/or spread of resistance. We investigated the in vitro activity of and selection of resistance to zoliflodacin alone and in combination with six gonorrhoea therapeutic antimicrobials against N. gonorrhoeae. METHODS: The international gonococcal reference strains WHO F (WT) and WHO O, WHO V and WHO X (strains with different AMR profiles) were examined. Zoliflodacin was evaluated alone or combined with ceftriaxone, cefixime, spectinomycin, gentamicin, tetracycline, cethromycin or sitafloxacin in chequerboard assays, time-kill curve analysis and selection-of-resistance studies. RESULTS: Zoliflodacin alone or in combination with all six antimicrobials showed rapid growth inhibition against all examined strains. The time-kill curve analysis indicated that tetracycline or cethromycin combined with zoliflodacin can significantly decrease the zoliflodacin kill rate in vitro. The frequency of selected zoliflodacin-resistance mutations was low when evaluated as a single agent and further reduced for all antimicrobial combinations. All resistant mutants contained the GyrB mutations D429N, K450T or K450N, resulting in zoliflodacin MICs of 0.5-4 mg/L. CONCLUSIONS: Zoliflodacin, alone or in combination with sexually transmitted infection therapeutic antimicrobials, rapidly kills gonococci with infrequent resistance emergence. Zoliflodacin remains promising for gonorrhoea oral monotherapy and as part of dual antimicrobial therapy with low resistance emergence potential. A Phase III trial evaluating efficacy and safety of zoliflodacin for uncomplicated gonorrhoea treatment is planned in 2019.

Plant Extracts Display Synergism with Different Classes of Antibiotics.

One manner in which plant-derived compounds exert their antibiotic potential is the synergism, a positive interaction between two compounds. Studies indicate that the use of plant extracts combined with antimicrobials may promote a significant reduction of the minimum inhibitory concentrations of antibiotics for bacterial strains. This study aimed to evaluate the activity of plant extracts and antibiotics as well as their combination on Staphylococcus aureus. The activity of 15 plant extracts was evaluated using diffusion assay. The minimum inhibitory concentrations (MICs) and the interactions between the extracts and antibiotics as well as compound emodin were evaluated with the checkerboard method. The active extracts were a hexane extract of the leaves of Baccharis dracunculifolia and the ethanol extracts of the leaves of Plectranthus ornatus, Inga edulis, Salvia officinalis and Senna macranthera. The Plectranthus ornatus extract displayed synergism with ampicillin (a ß-lactam), kanamycin and gentamicin (aminoglycosides), with 8-fold reductions in the MIC. The same reduction was observed for the extracts of Salvia officinalis and Senna macranthera, which displayed the lowest MIC. Using these combinations resulted in a reduction in the minimum dose required for effective antimicrobial effects, which is interesting because it may decrease both the risk of side effects and the costs of treatment.

Congenital Bilateral Eyelid Eversion and Chemosis: A Case Study.

This case reports the findings and management of a late preterm female infant born with congenital bilateral eyelid eversion with chemosis. The pathogenic process remains unknown but typically presents at birth, predominantly affecting the upper eyelid of both eyes. Black males, patients with trisomy 21, and collodion infants have a higher incidence of eyelid eversion. Treatment modalities range from conservative therapy including eye patching with antibiotic and lubricating ointment to invasive surgical eyelid suturing. In this case report, successful resolution of chemosis and eyelid inversion occurred with conservative management.

A new class of synthetic retinoid antibiotics effective against bacterial persisters.

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

Busting the Myth of "Static vs Cidal": A Systemic Literature Review.

We sought to determine if clinical data validate the dogma that bactericidal antibiotics are more clinically effective than bacteriostatic agents. We performed a systematic literature review of published, randomized, controlled trials (RCTs) that compared a bacteriostatic agent to a bactericidal agent in the treatment of clinical, bacterial infections. Of 56 identified trials published since 1985, 49 found no significant difference in efficacy between bacteriostatic and bactericidal agents. In 6 trials it was found that the bacteriostatic agent was superior to the bactericidal agent in efficacy. Only 1 trial found that the bactericidal agent was superior; in that case, the inferiority of the static agent was explainable by underdosing of the drug based on pharmacokinetic-pharmacodynamic analysis. Thus, virtually all available data from high-quality, RCTs demonstrate no intrinsic superiority of bactericidal compared to bacteriostatic agents. Other drug characteristics such as optimal dosing, pharmacokinetics, and tissue penetration may be more important efficacy drivers.

[Analysis of the efficiency of antimicrobial treatment for community-acquired pneumonia in clinical practice]. / Analiz éffektivnosti antimikrobnoi terapii vnebol'nichnoi pnevmonii v klinicheskoi praktike.

AIM: To analyze actual drug consumption based on the defined daily dose (DDD analysis) and to analyze the utilization of drugs based on their proportion of the total defined daily doses (DU90% analysis) for the antimicrobial therapy of community-acquired pneumonia (CAP) in clinical practice at a hospital in Russia. MATERIAL AND METHODS: The investigation materials were the data of 117 case histories of male (51.3%) and female (48.7%) patients hospitalized with CAP at Nizhny Novgorod City Clinical Hospital Five in 2015. The investigation enrolled all the patients admitted to the hospital over the analyzed period. DDD analysis and DU90% analysis were used as study methods. RESULTS: DDD analysis and DU90% analysis of antimicrobial therapy for CAP were carried out at the hospital in clinical practice during a year. The annual number of defined daily doses (NDDD) for antimicrobial drugs, the number of defined daily doses per 100 bed-days (NDDD/100 bed-days), and a drug load (g) per 1000 CAP patients per day and per CAP patient per year were determined. The largest NDDD/year for CAP treatment with ceftriaxone was 376 g, or 43.43 NDDD/100 bed-days, which is much higher than that with other antimicrobial agents. The daily drug load of ceftriaxone per 1,000 CAP patients was 8.8 g, which exceeds that of moxifloxacin by 18.7 times, azithromycin and levofloxacin by 5 times, and ampicillin/sulbactam by 2.3 times. The daily drug load of ceftriaxone per CAP patient was 3.2 g, which exceeds that of of ampicillin/sulbactam by 2.3 times, levofloxacin and azithromycin by 5 times, and moxifloxacin by 19 times. CONCLUSION: It may be recommended that the proportion of cephalosporins as drugs that promote the rise of resistance in microbes and their production of extended-spectrum ß-lactamases should be further limited, the proportion of penicillins be extended, and the administered ampicillin/sulbactam be added, for example, by amoxicillin/clavulanate. Penicillins contribute to the rise of resistance to a lesser degree, and the use of two different penicillin molecules specified in the guidelines for the treatment of CAP will be able to slow the process further. By the same reasoning, it is also advisable to use cefuroxime (second-generation cephalosporins) along with ceftriaxone in patients in stable condition, without impairing vital functions.

Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance.

Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.

Multidrug-Resistant Enterococcal Infections: New Compounds, Novel Antimicrobial Therapies?

Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E. faecium and E. faecalis. These new antibacterial agents include teixobactin (targeting lipid II and lipid III), lipopeptides derived from nisin (targeting lipid II), dimeric vancomycin analogues (targeting lipid II), sortase transpeptidase inhibitors (targeting the sortase enzyme), alanine racemase inhibitors, lipoteichoic acid synthesis inhibitors (targeting LtaS), various oxazolidinones (targeting the bacterial ribosome), and tarocins (interfering with teichoic acid biosynthesis). The targets of these novel compounds and mode of action make them very promising for further antimicrobial drug development and future treatment of Gram-positive bacterial infections. Here we review current knowledge of the most favorable anti-enterococcal compounds along with their implicated modes of action and efficacy in animal models to project their possible future use in the clinical setting.

[ANALYSIS OF MICROFLORA OF PLEURAL CAVITY IN PLEURAL EMPYEMA].

In the pleural empyema (PE) treatment, not depending on introduction of multiple operative procedures and the medicinal preparations application, some issues remain unsolved, including the infection agents verification, the most rapid bronchial fistula elimination and the lung volume restoration. The EP infection agents spectrum, their sensitivity to preparations were revealed, as well as the enhanced rate of the methicillin-resistant stamms (MRSA) and the microorganisms associations verification. A reduction of the infection agents sensitivity towards "simple" antibacterial preparations was established, so the physicians, treating PE, must prescribe "hard" antibiotics, what enhances its cost.

[CHARACTERISTICS OF ANTIBIOTICORESISTANCE OF MICROFLORA IN A COMBAT (THE GUN-SHOT ANO THE MINE-EXPLOSION) WOUNDS OF THE EXTREMITIES].

Abstract Results of bacteriological investigations of a gun-shot and a mine-explosion woundings of the extremities were analyzed in Military-Medical Clinical Centres (MMCC) of Kyiv, Lviv and Vinnytsya. Spectrum of the allotted microorganisms and profile of their antibioticoresistance were disclosed. The patterns of resistance were determined in accordance to offering of international experts of European Committee on Antimicrobial Susceptibility Testing (EUCAST). Dominating microflora in a Chief MMCC (Kyiv) and MMCC of a Western Region (Lviv) were various species of the Enterobacteriaceae and P. aeruginosa families, while in MMCC of a Central Region (Vinnytsya)--a gramm-negative non-fermentative bacilli of the Acinetobacter genus and Pseudomonas genus. The majority (79.5%) of isolates were characterized by polyresistance for antibiotics. Maximal quantity of strains with a widened spectrum of resistance was revealed in 2 - 3 weeks after a wounding--in 71.4 and 96.9% accordingly.