Surveillance of penicillin resistance of Neisseria meningitidis strains from invasive infections between 2013 and 2018 in Turkey.

Neisseria meningitidis (N. meningitidis) is regarded as the leading cause of bacterial meningitis in many regions of the world. The empiric antimicrobial treatment is mainly based on antimicrobial resistance and patient characteristics. We aimed to analyze susceptibility patterns of N. meningitidis strains isolated in Turkey. Invasive meningococci collected in a multicenter, hospital-based, epidemiological surveillance study of pediatric (0-18 years of age) bacterial meningitis cases between 2013 and 2018 were studied. Five isolates (8.7%) displayed resistance to penicillin-G, while 13 isolates (22.8%) had intermediate susceptibility. All isolates were cefotaxime and rifampin susceptible. The data shows appropriateness of third-generation cephalosporins in empirical use for meningococcal infections in children. Since Turkey is located in a transition zone geographically, surveillance reports are very crucial.

The activity of 16 new hydantoin compounds on the intrinsic and overexpressed efflux pump system of Staphylococcus aureus.

AIM: To evaluate a new series of 16 hydantoin derivatives for activity against the intrinsic and overexpressed efflux pumps of the ATTC 25923 Staphylococcus aureus and the clinical Staphylococcus aureus HPV-107 strain, respectively. MATERIALS AND METHODS: The hydantoin compounds were evaluated for activity against the efflux pumps of the ATTC 25923 S. aureus and the clinical S. aureus HPV-107 strains by the aid of the automated ethidium bromide method. Compounds that inhibited the efflux pumps of either strain were evaluated for ability to reduce or reverse resistance of these strains to oxacillin. RESULTS: Although most of the hydantoins inhibited the efflux pumps of the ATTC strain, none reduced the resistance of this strain to oxacillin. In contrast, the inhibition of the Qac efflux pump present in HPV-107 was inhibited to some degree, by much higher concentrations of the hydantoin compounds than that needed for similar activity against the ATTC strain; only hydantoin PI8a significantly reduced the minimum inhibitory concentration of oxacillin against the HPV-107 strain. CONCLUSION: Hydantoin compound PI8a may have potential for therapy of a methicillin-resistant S. aureus infection whose multidrug-resistant phenotype is due to overexpression of an efflux pump.

Ceftaroline versus ceftriaxone in a highly penicillin-resistant pneumococcal pneumonia rabbit model using simulated human dosing.

Ceftaroline (CPT) is a new cephalosporin exhibiting bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae (MDRSP), as well as common Gram-negative pathogens. This study investigated the in vivo efficacy of a 48-hour simulated human dose regimen of CPT compared with ceftriaxone (CRO) against isolates of S. pneumoniae with different susceptibilities to penicillin in a rabbit pneumonia model. Three S. pneumoniae strains were used: CRO-susceptible penicillin-susceptible S. pneumoniae (CRO-S PSSP), CRO-susceptible penicillin-intermediate S. pneumoniae (CRO-S PISP), and CRO-resistant penicillin-resistant S. pneumoniae (CRO-R PRSP). Animals were randomized to the control group (no treatment) (n = 22) or to a group given intravenous (IV) CPT human equivalent (HE) dosage (600 mg/12 h; n = 19) or IV CRO HE dosage (1 g/24 h; n = 19). The total doses needed to achieve the HE dosage were 71 and 82 mg/kg of body weight/24 h for CRO and CPT, respectively. One group of rabbits infected with the CRO-R PRSP strain received intramuscular (IM) administration of CPT (5 or 20 mg/kg twice daily; n = 5 for each). Evaluation of efficacy was based on bacterial counts in the lungs and spleen. For IV CPT and IV CRO, the mean areas under the concentration-time curves from 0 to 24 h (AUC(0-24)s) were 155 and 938 mg · h/liter, respectively, the maximum concentrations in serum (C(max)s) were 20 and 158 mg/liter, respectively, and the minimum concentrations in serum (C(min)s) were 1.3 and 6 mg/liter, respectively. Both agents effectively treated pulmonary infections caused by CRO-S PSSP or CRO-S PISP with complete bacterial eradication in the lungs and spleen after 2 days of treatment. Against PRSP, CPT demonstrated excellent bactericidal activity, reducing bacterial counts in the lungs and spleen by approximately 8 and 4 log units, respectively (P < 0.001); CRO treatment resulted in a 2-log-unit reduction in the bacterial counts in lungs that did not reach statistical significance. Twice-daily IM CPT (5 mg/kg) reduced the bacterial burden by approximately 6 log units in the lungs and 3 log units in the spleen, and the 20-mg/kg dosage effectively eradicated PRSP infection. These findings further validate the in vivo bactericidal activity of CPT against pneumococci.

Phenolic compounds from the seeds of Garcinia dulcis.

Dulcisxanthone G, 1,3,6-trihydroxy-2-(2,3-dihydroxy-3-methylbutyl)-7-methoxy-8-(3-methyl-2-butenyl)xanthone, together with 13 known compounds were isolated from the seeds of Garcinia dulcis. Their structures were determined by analysis of 1D and 2D NMR spectroscopic data. The activities on antibacterial and antioxidation of the isolated compounds were examined.

[Betalactam antibiotics combined with bectalactamases inhibitors. Amoxicillin-sulbactam]. / Betalactámicos con inhibidores de betalactamasas. Amoxicilina-sulbactam.

Betalactamases production is one of the main bacterial resistance mechanisms to betalactam antibiotics. The use of bectalactamases inhibitors combined with betalactam antibiotics allows the inactivation of certain betalactamases produced by Gram positive, Gram negative and anaerobic organisms, and even by mycobacteria. Betalactamases inhibitors are an improved therapeutic alternative compared with the other betalactam since, in most cases, they cover a wider antimicrobial spectrum than their analogues. Betalactamases enzimatic activity is specifically directed to the betalactam ring hydrolisis, producing a compound without antibacterial activity. According to their genomic position within microorganisms, betalactamases can be either chromosomic or plasmidic. Currently there are three betalactamases inhibitors locally available: clavulanic acid, sulbactam and tazobactam. Of them, only sulbactam has an intrinsic antimicrobial activity against penicillin binding proteins. The clinical experience from over 20 years confirms that the combination of betalactam antibiotics is effective in the empirical initial treatment of respiratory, intraabdominal, urinary tract and gynecologic infections, including those of polymicrobial origin. In the specific case of amoxicillin-sulbactam, experiences have shown the effectiveness of the combination in the treatment of peritonsillar abscess, otitis media, sinusitis, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonar disease (COPD), urinary tract infection and obstetric/gynecologic infections. The spectrum and pharmacologic properties of this combination makes it also an excellent option for the treatment of skin/soft tissue and intraabdominal infections.

Betalactámicos con inhibidores de betalactamasas: Amoxicilina-sulbactam / Betalactam antibiotics combined with bectalactamases inhibitors: Amoxicillin-sulbactam

La producción de betalactamasas constituye uno de los principales mecanismos de resistencia bacteriana a los antibióticos betalactámicos. La utilización de inhibidores de betalactamasas en combinación con antibióticos betalactámicos permite la inactivación de determinadas betalactamasas producidas por gérmenes Gram positivos, Gram negativos, anaerobios, y aun por micobacterias. Los inhibidores de betalactamasas representan una alternativa terapéutica mejorada respecto del resto de los betalactámicos al asegurar, en la mayoría de los casos, un mayor espectro antimicrobiano comparado con el de sus análogos. La actividad enzimática de las betalactamasas está dirigida específicamente a la hidrólisis del anillo betalactámico, con producción de un compuesto sin actividad antibacteriana. De acuerdo con su posición genómica dentro de los microorganismos, las betalactamasas pueden ser cromosómicas o plasmídicas. Actualmente existen tres inhibidores de betalactamasas localmente disponibles: ácido clavulánico, sulbactam y tazobactam. De ellos, sólo el sulbactam posee actividad antimicrobiana intrínseca sobre las proteínas ligadoras de penicilina. La experiencia clínica acumulada durante más de 20 años confirma que las combinaciones de betalactámicos-inhibidores de betalactamasas son efectivas en el tratamiento empírico inicial de infecciones respiratorias, intraabdominales, urinarias y ginecológicas, incluidas las de origen polimicrobiano. En el caso particular de amoxicilina-sulbactam, la evidencia citada indica que esta combinación es efectiva para el tratamiento de absceso periamigdalino, otitis media, sinusitis, neumonía extrahospitalaria, exacerbación aguda de enfermedad pulmonar obstructiva crónica (EPOC), infección del tracto urinario e infecciones ginecoobstétricas. Por su espectro y propiedades farmacológicas, la combinación amoxicilina-sulbactam constituye una excelente opción también para el tratamiento de infecciones de piel y partes blandas e infecciones intraabdominales.

Betalactamases production is one of the main bacterial resistance mechanisms to betalactam antibiotics. The use of bectalactamases inhibitors combined with betalactam antibiotics allows the inactivation of certain betalactamases produced by Gram positive, Gram negative and anaerobic organisms, and even by mycobacteria. Betalactamases inhibitors are an improved therapeutic alternative compared with the other betalactam since, in most cases, they cover a wider antimicrobial spectrum than their analogues. Betalactamases enzimatic activity is specifically directed to the betalactam ring hydrolisis, producing a compound without antibacterial activity. According to their genomic position within microorganisms, betalactamases can be either chromosomic or plasmidic. Currently there are three betalactamases inhibitors locally available: clavulanic acid, sulbactam and tazobactam. Of them, only sulbactam has an intrinsic antimicrobial activity against penicillin binding proteins. The clinical experience from over 20 years confirms that the combination of betalactam antibiotics is effective in the empirical initial treatment of respiratory, intraabdominal, urinary tract and gynecologic infections, including those of polymicrobial origin. In the specific case of amoxicillin-sulbactam, experiences have shown the effectiveness of the combination in the treatment of peritonsillar abscess, otitis media, sinusitis, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonar disease (COPD), urinary tract infection and obstetric/ gynecologic infections. The spectrum and pharmacologic properties of this combination makes it also an excellent option for the treatment of skin/soft tissue and intraabdominal infections.

[Nasal carriage of Streptococcus pneumoniae in elderly subjects according to vaccination status]. / Portación nasal de Streptococcus pneumoniae en adulto mayor y su respuesta frente a la vacunación antineumocócica.

BACKGROUND: S pneumoniae is the main cause of community-acquired pneumonia in the elderly, group that concentrates 95% of deaths. AIM: To assess the prevalence of nasal carriage of S pneumoniae in institutionalized elderly patients. MATERIAL AND METHODS: One hundred eighteen institutionalized subjects aged over 60 years (65 males) were enrolled. Since they were also participating in a controlled protocol related to the immunogenicity of an anti-pneumococcal vaccine, our investigation was also blind and randomized. According to randomization, they received pneumococcal or tetanic vaccine. Nasal swab cultures were taken at the beginning of the trial and two months after vaccination. According to recommended methods, we identified S pneumoniae, the serotypes and their antimicrobial susceptibility. RESULTS: In the first nasal sample, 16% of subjects were positive for S pneumoniae. The second sample was positive in 12%. Of the 33 isolated serotypes, 9.1% demonstrated intermediate resistance to penicillin and 3.3% were resistant to chloramphenicol. CONCLUSIONS: The study demonstrated a greater percentage of colonized patients than in the general population. The isolated serotypes are the same that cause invasive diseases in this age group, according to data of the Institute of Public Health of Chile. There were no differences in the percentage of colonization between subjects vaccinated against S pneumoniae and control groups, after two months of follow up. Isolated strains had a low resistance to penicillin. High level resistance was not observed.

Portación nasal de Streptococcus pneumoniae en adulto mayor y su respuesta frente a la vacunación antineumocócica / Nasal carriage of Streptococcus pneumoniae in elderly subjects according to vaccination status

Background: S pneumoniae is the main cause of community-acquired pneumonia in the elderly, group that concentrates 95 percent of deaths. Aim: To assess the prevalence of nasal carriage of S pneumoniae in institutionalized elderly patients. Material and methods: One hundred eighteen institutionalized subjects aged over 60 years (65 males) were enrolled. Since they were also participating in a controlled protocol related to the immunogenicity of an anti-pneumococcal vaccine, our investigation was also blind and randomized. According to randomization, they received pneumococcal or tetanic vaccine. Nasal swab cultures were taken at the beginning of the trial and two months after vaccination. According to recommended methods, we identified S pneumoniae, the serotypes and their antimicrobial susceptibility. Results: In the first nasal sample, 16 percent of subjects were positive for S pneumoniae. The second sample was positive in 12 percent. Of the 33 isolated serotypes, 9.1 percent demonstrated intermediate resistance to penicillin and 3.3 percent were resistant to chloramphenicol. Conclusions: The study demonstrated a greater percentage of colonized patients than in the general population. The isolated serotypes are the same that cause invasive diseases in this age group, according to data of the Institute of Public Health of Chile. There were no differences in the percentage of colonization between subjects vaccinated against S pneumoniae and control groups, after two months of follow up. Isolated strains had a low resistance to penicillin. High level resistance was not observed.

[Action of combinations of ampiox and a quinoline derivative on penicillin-resistant staphylococcal strains]. / Deistvie sochetanii ampioksa i proizvodnogo khinolina na penitsillinoustoichivye shtammy stafilokokka.

The effect of ampiox combination with a quinoline derivative (QD) on penicillin resistant strains of Staphylococcus was studied. Combination of ampiox and QD had in vitro a synergistic action. It was shown that the combined use of ampiox in a dose of 5 mg/kg and QD in a dose of 10 mg/kg had a pronounced therapeutic effect in staphylococcal septicemia of albino mice: 95 per cent prevention of death in the experimental animals and lower contamination of the animal internal organs. It was noted that ampiox and QD had different mechanisms of action on the bacterial cell. Therefore, their combination may be used for increasing antistaphylococcal activity of the antibiotic drug.

Inhibition of beta-lactamase-induced resistance in soft-tissue infections.

Sulbactam ([CP45,899] penicillanic acid sulfone) inhibits many of the beta-lactamases commonly found to be the cause of penicillin resistance. This agent was combined with either penicillin G potassium or ampicillin sodium in the treatment of 97 patients admitted with serious soft-tissue infections. Fifty-one of the infections were caused by at least one bacteria resistant to the antibiotic alone. Staphylococcus aureus was the most common pathogen (48 isolations) followed by the coliforms (30 isolations). Ninety percent of the isolates that were tested produced beta-lactamase. Susceptibility studies showed a high degree of resistance to the penicillin alone that was significantly lowered by the addition of sulbactam. The overall clinical results showed 81% of the infections to be either well controlled or cured. Three patients failed to show improvement. Thirteen patients showed transitory increases relatively safe and efficacious in the treatment of soft-tissue infection caused by penicillin-resistant and penicillin-susceptible organisms.

[Chemotherapeutic activity of benzylpenicillin in combination with a perhydroacridine derivative studied in experimental staphylococcal infection]. / Izuchenie khimioterapevticheskoi aktivnosti benzilpenitsillina v sochetanii s proizvodnym pergidroakridina pri éksperimental'noi stafilokokkovoi infektsii.

Chemotherapeutic activity of various benzylpenicillin combinations with 10-nitro-so-trans-anti-cys-perhydroacridine (MT-2) was studied on 2 experimental staphylococcal infections caused by pathogenic penicillin resistant strains of staphylococci. It was found that the combined use of the antibiotic and MT-2 in doses of 25-100 and 12.5 mg/kg respectively administered subcutaneously increased the therapeutic effect of benzylpenicillin as compared to the antibiotic used alone. The oral use of MT-2 in a dose of 400 mg/kg also increased the therapeutic action of benzylpenicillin used in a dose of 100 mg/kg subcutaneously simultaneously with MT-2. A favourable effect of ointments containing MT-2 in a concentration of 10-20 per cent and benzylpenicillin in a dose of 50 000 or 100 000 units per 1 g of the ointment was noted in treatment of mice with localized staphylococcal infection.