Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in Turkey: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

OBJECTIVES: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Turkey. METHODS: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: A total of 179 S. pneumoniae and 239 H. influenzae isolates were collected. Few (27.9%) pneumococci were penicillin susceptible by CLSI oral or EUCAST low-dose breakpoints, but by EUCAST high-dose or CLSI IV breakpoints 84.4% were susceptible. The most active antibiotics (excluding penicillin IV) by CLSI breakpoints were fluoroquinolones (98.9% of isolates susceptible), ceftriaxone (83.2%), amoxicillin (78.8%) and amoxicillin/clavulanic acid (78.8%). Pneumococcal susceptibility to amoxicillin and amoxicillin/clavulanic acid was lower using EUCAST low-dose breakpoints (49.7%), although susceptibility increased when using EUCAST high-dose (57.0%-58.1%) and PK/PD (78.8%-87.7%) breakpoints. Twenty-three H. influenzae isolates were ß-lactamase positive, with 11 characterized as ß-lactamase negative and ampicillin resistant following EUCAST criteria and 5 by CLSI criteria. Generally antibiotic susceptibility was high using CLSI breakpoints: ≥92.9% for all antibiotics except ampicillin (87% by CLSI and EUCAST breakpoints) and trimethoprim/sulfamethoxazole (67.4% and 72% by CLSI and EUCAST breakpoints, respectively). Susceptibility using EUCAST breakpoints (where these are published) was similar, except for cefuroxime (oral) with 3.8% of isolates susceptible. PK/PD breakpoints indicated low susceptibility to macrolides (5.9%-10%) and cefaclor (13%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. CONCLUSIONS: Antibiotic susceptibility of S. pneumoniae was generally low, which is in keeping with evidence of inappropriate and high antibiotic use in Turkey. H. influenzae susceptibility was high. These data are important for empirical therapy of CA-RTIs.

Results from the Survey of Antibiotic Resistance (SOAR) 2011-13 in Turkey.

OBJECTIVES: Data are presented from the Survey of Antibiotic Resistance (SOAR) for respiratory tract infection pathogens collected in 2011-13 from Turkey. METHODS: MICs were determined using Etest(®). Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) interpretive criteria. RESULTS: Rates of antibiotic susceptibility were very low among 333 isolates of Streptococcus pneumoniae tested: penicillin 38% using CLSI (oral) and EUCAST breakpoints; erythromycin 51% using CLSI and EUCAST criteria; and cefuroxime 64.6% using CLSI and PK/PD and 46.9% using EUCAST. Of the isolates, >90% were susceptible to amoxicillin/clavulanic acid, ceftriaxone (except using EUCAST criteria: 76%), levofloxacin and high-dose intravenous penicillin. Among 339 Haemophilus influenzae isolates, 6.8% were ß-lactamase positive while 9.1% were ß-lactamase negative but ampicillin resistant (BLNAR) by CLSI (14.7% by EUCAST) criteria. Amoxicillin/clavulanic acid susceptibility was ∼90% by CLSI (with or without BLNAR adjustment, EUCAST and high-dose PK/PD) but lower, at 82.9%, by EUCAST with BLNAR adjustment. Levofloxacin susceptibility was 96% using all three breakpoints. Dramatic differences in rates of susceptibility, depending on the breakpoints used, were seen for cefaclor [94% by CLSI (86.4% BLNAR adjusted), 23% by PK/PD] and cefuroxime [97% by CLSI (89.1% BLNAR adjusted), 85% by PK/PD, 15% by EUCAST (13.0% BLNAR adjusted)]. Streptococcus pyogenes (n = 222) and Moraxella catarrhalis (n = 40) isolates remained highly susceptible to amoxicillin/clavulanic acid, cephalosporins and levofloxacin, with only erythromycin susceptibility dropping below 95% for S. pyogenes. CONCLUSIONS: Overall, amoxicillin/clavulanic acid and levofloxacin were the most active antibiotics based on all three breakpoints against these pathogens. Although susceptibility was not universally low in Turkey, high resistance rates were found in S. pneumoniae and, when using PK/PD and EUCAST breakpoints, in other respiratory pathogens.

Results from the Survey of Antibiotic Resistance (SOAR) 2002-09 in Turkey.

OBJECTIVES: To investigate changes in antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae from the Survey of Antibiotic Resistance (SOAR) in community-acquired respiratory tract infections (CA-RTIs) between 2002 and 2009 in Turkey. METHODS: Previously published SOAR data were used for this analysis. MICs were determined using Etest(®) gradient strips or disc diffusion. Susceptibility against a range of antimicrobial agents was assessed using CLSI breakpoints. RESULTS: A total of 900 S. pneumoniae isolates were analysed: 2002-03 (n = 75), 2004-05 (n = 301) and 2007-09 (n = 524). Four antibiotics were tested consistently throughout and three showed a statistically significant decrease in susceptibility (P < 0.0001): penicillin (74.7% susceptible in 2002-03; 67.8% in 2004-05; and 47.2% in 2007-09); cefaclor (85.3% in 2002-03; 78.7% in 2004-05; and 53.5% in 2007-09) and clarithromycin (85.3% in 2002-03; 82.7% in 2004-05; and 61.9% in 2007-09). Susceptibility to amoxicillin/clavulanic acid did not significantly change (100% in 2002-03; 98.7% in 2004-05; and 97.7% in 2007-09). A total of 930 H. influenzae isolates were analysed: 2002-03 (n = 133), 2004-05 (n = 379) and 2007-09 (n = 418). Four antibiotics were also consistently tested: ampicillin, amoxicillin/clavulanic acid, clarithromycin and cefaclor. All showed >90% susceptibility, but only cefaclor susceptibility significantly reduced (P < 0.0001) over time (99.2% in 2002-03; 96.3% in 2004-05; and 90.4% in 2007-09). CONCLUSIONS: In S. pneumoniae from Turkey, there has been a clear statistically significant reduction in susceptibility to key antibiotics since 2002, but not to amoxicillin/clavulanic acid (or amoxicillin). However, susceptibility in H. influenzae remained stable. Continued surveillance is required to monitor future changes in antibiotic susceptibility for CA-RTI bacteria.

In vitro activity of fluoroquinolones against common respiratory pathogens.

The treatment of respiratory infections is often empiric, necessitating the use of agents with a broad range of antimicrobial activity. The fluoroquinolones, having activity against common respiratory pathogens, fit this description. New fluoroquinolones have been developed in an attempt to improve the in vitro activity against a wide variety of respiratory tract pathogens. The objective of the study is to compare in vitro activity of newest fluoroquinolones, gatifloxacin and moxifloxacin, with levofloxacin and ciprofloxacin using three major respiratory pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Minimum inhibitory concentrations (MICs) of four fluoroquinolones were tested against 93 S pneumoniae, 62 H influenzae and 60 M catarrhalis, ie 215 isolates by the E-test method. National Committee for Clinical Laboratory Standards (NCCLS)-approved interpretive criteria were used throughout. All isolates were susceptible to the tested fluoro-quinolones. Ninety per cent of S pneumoniae strains were inhibited by ciprofloxacin at concentrations of 2 mg/L. The gatifloxacin and moxifloxacin MICs were lower than the ciprofloxacin and levofloxacin MICs against S pneumoniae. In contrast to S pneumoniae, in vitro activities of gatifloxacin and moxifloxacin offered no apparent advantages over ciprofloxacin and levofloxacin for H influenzae and M catarrhalis.

In vitro activity of daptomycin alone and in combination with various antimicrobials against Gram-positive cocci.

The increasing prevalence of resistant Gram-positive cocci requires the need to search for more effective agents and synergistic combinations. Forty-two vancomycin-resistant Enterococcus faecium (VREF), 30 methicillin-resistant Staphylococcus aureus (MRSA) and 36 Staphylococcus epidermidis (MRSE) strains were studied. Minimum inhibitory concentrations (MICs) were determined and synergy testing was performed by using E test for daptomycin, ampicillin-sulbactam, piperacillin-tazobactam and ticarcillin-clavulanate against staphylococci; for daptomycin, ampicillin, rifampin, and gentamicin against enterococci. Daptomycin in combination with ampicillin, rifampin, and gentamicin was tested against enterococci; daptomycin in combination with ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin-clavulanate was tested against staphylococci. Interaction categories were defined by the fractional inhibitory concentration (FIC) index. All strains of staphylococci and enterococci were susceptible to daptomycin. All three combinations showed synergy against more than 70% of the MRSA strains. Daptomycin in combination with ampicillin, rifampin, and gentamicin against enterococci showed synergies of 64.2%, 57.1% and 21.4%, respectively. This study indicates that daptomycin alone and combined with beta-lactams seems to be effective against MRSA, but further in vitro and in vivo studies on the subject are required before clinical use can be recommended.

Does pharmaconutrition with L-arginine and/or alpha-tocopherol improve the gut barrier in bile duct ligated rats?

BACKGROUND/AIM: Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and alpha-tocopherol supplementation in bile duct ligated rats. METHODS: Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administered alpha-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) alpha-tocopherol. Nitric oxide, malondialdehyde, and alpha-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. RESULTS: The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood alpha-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. CONCLUSIONS: An obvious effect of alpha-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or alpha-tocopherol supplementation did not seem to improve the gut barrier in our model.

In vitro activity of fluoroquinolones against common respiratory pathogens / La actividad in vitro de las fluorquinolonas contra los patógenos respiratorios

The treatment of respiratory infections is often empiric, necessitating the use of agents with a broad range of antimicrobial activity. The fluoroquinolones, having activity against common respiratory pathogens, fit this description. New fluoroquinolones have been developed in an attempt to improve the in vitro activity against a wide variety of respiratory tract pathogens. The objective of the study is to compare in vitro activity of newest fluoroquinolones, gatifloxacin and moxifloxacin, with levofloxacin and ciprofloxacin using three major respiratory pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Minimum inhibitory concentrations (MICs) of four fluoroquinolones were tested against 93 S pneumoniae, 62 H influenzae and 60 M catarrhalis, ie 215 isolates by the E-test method. National Committee for Clinical Laboratory Standards (NCCLS)-approved interpretive criteria were used throughout. All isolates were susceptible to the tested fluoro-quinolones. Ninety per cent of S pneumoniae strains were inhibited by ciprofloxacin at concentrations of 2 mg/L. The gatifloxacin and moxifloxacin MICs were lower than the ciprofloxacin and levofloxacin MICs against S pneumoniae. In contrast to S pneumoniae, in vitro activities of gatifloxacin and moxifloxacin offered no apparent advantages over ciprofloxacin and levofloxacin for H influenzae and M catarrhalis.

La terapia de las infecciones respiratorias es a menudo empírica, y exige por ende el uso de agentes con un amplio espectro de actividad antimicrobiana. Por su actividad contra los patógenos respiratorios comunes, las fluorquinolonas se ajustan a esta descripción. Nuevas fluorquinolonas han sido desarrolladas, en un intento por mejorar la actividad in vitro contra una variedad de patógenos de las vías respiratorias. El objetivo de este estudio es comparar la actividad in vitro de las fluorquinolonas más recientes – la gatifloxacina y la moxifloxacina – con la levofloxacina y la ciprofloxacina, usando tres de los más importantes patógenos respiratorios: Streptococcus pneumoniae, Haemophilus influenzae y Moraxella catarrhalis. Las concentraciones inhibitorias mínimas (CIMs) de las cuatro fluorquinolonas fueron sometidas a prueba contra 93 S pneumoniae, 62 H influenzae y 60 M catarrhalis, para un total de 215 aislados mediante el método de E-test. En todos los casos se aplicaron criterios interpretativos aprobados por el Comité Nacional para Normas del Laboratorio Clínico (NCCLS). Todos los aislados resultaron sensibles a las fluorquinolonas ensayadas. El noventa por ciento de las cepas de S pneumoniae fueron inhibidas por la ciprofloxacina a concentrationes of 2 mg/L. Las CIMs de la gatifloxacina y la moxifloxacina fueron más bajas que las CIMs de la ciprofloxacina y la levofloxacina contra S pneumoniae. En contraste con S pneumoniae, la actividad in vitro de la gatifloxacina y la moxifloxacina no ofrecieron ventajas aparentes por encima de la ciprofloxacina y la levofloxacina frente a H influenzae y M catarrhalis.

Experience with teicoplanin in the treatment of neonatal staphylococcal sepsis.

We aimed to evaluate retrospectively the clinical and bacteriological efficacy and potential side-effects of teicoplanin treatment in neonates with proven staphylococcal infection. There were 37 episodes of staphylococcal septicaemia in neonates with a mean gestational age of 34.2 +/- 2.3 weeks; 26 were caused by coagulase-negative staphylococcal (CoNS) sepsis and 11 by Staphylococcus aureus sepsis. All episodes were treated with teicoplanin (intravenous loading dose 16 mg/kg followed by a maintenance dose of 8 mg/kg daily). The methicillin resistance and antibiotic susceptibilities of both micro-organisms were evaluated. Bacterial eradication was achieved in 89.1% of cases and mortality was 16.2%. The mean duration of treatment of the survivors was 11.6 +/- 2.3 days. There were no drug-related adverse events and the biochemical and haematological tests showed no clinically significant changes in relation to teicoplanin therapy. Our results suggest that teicoplanin is highly effective in neonatal staphylococcal sepsis.

Effect of granulocyte-macrophage colony stimulating factor on bacterial translocation after experimental obstructive jaundice.

OBJECTIVE: To investigate the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on bacterial translocation promoted by obstructive jaundice. DESIGN: Controlled animal study. SETTING: University hospital, Turkey. ANIMALS: 30 male Wistar albino rats. INTERVENTIONS: The first group (n = 10) was the sham operation (control) group, and the second and the third (n = 10 each) had common bile duct (CBD) ligation and division under sterile conditions. The third group were also treated with GM-CSF 200 ng subcutaneously daily between the fifth and ninth postoperative days. All animals were killed on the tenth day, and evaluated biochemically and histopathologically. Mesenteric lymph nodes were cultured under aerobic conditions. MAIN OUTCOME MEASURES: Biochemical analysis, histopathological evaluation, and aerobic cultures. RESULTS: There was no bacterial translocation in either the control or GM-CSF groups, whereas Escherichia coli and Salmonella typhimurium were found in 4 and 2 animals, respectively in the ligation group. Although no aerobic bacteria was found in controls and the GM-CSF groups, bacterial translocation was 6/10 in the ligation alone group (p <0.01). CONCLUSION: Activation of inflammatory response with GM-CSF is highly effective in prevention of bacterial translocation in obstructive jaundice.

Comparative clinical and microbiological effects of subgingival metronidazole application in adult periodontitis; 12-months results.

The aim of the present study was to evaluate the clinical and microbiological effects of subgingival application of 25% metronidazole dental gel as an adjunct to scaling and root planing (SRP) in the treatment of adult periodontitis. Eighty teeth in 18 patients were evaluated using a split mouth design. The test teeth received SRP and a 25% metronidazole gel applied subgingivally on days 0 and 7. The control teeth received SRP only. Clinical and microbiological examinations were carried out before treatment and on weeks 1, 3, 7, 13, 26, 38 and 52 of the experimental period. Colony forming units of Porphyromonas gingivalis and Prevotella intermedia / Prevotella nigrescens were determined. Both treatments provided significant improvements in all the clinical and microbiological parameters (P<0.05). However, none of the differences between the study groups were statistically significant (P > 0.05). As a conclusion, the present study does not provide evidence in favour of the routine use of adjunctive metronidazole dental gel in the treatment of adult periodontitis.

Effects of H2 receptor blocking agents on bacterial translocation in burn injury.

We experimentally studied the effects of H2 receptor blockers (ranitidine) on bacterial translocation (BT) in 42 male albino rats. Sham group (Group I, n = 12 rats) were exposed to 21 degrees C water while Burn group (Group II, n = 15 rats) and Ranitidine group (Group III, n = 15 rats) were exposed to 95 degrees C hot water for 10 seconds to produce a full thickness burn in 30% of total body surface area. 300 mg/kg ranitidine was administered to Group III starting immediately after the burn injury. Rats were sacrificed on the fifth postburn day. Sham group gained weight while groups II and III had significant weight loss. Gastric pH increased with the administration of ranitidine. Both gram negative and total number of bacteria were found to be reduced in cecal stool cultures in ranitidine group. Significant increase in BT was observed in Group III, and translocating bacteria were found to be different in burn and ranitidine groups with a final conclusion that administration of ranitidine changes intestinal ecological equilibrium and promotes BT.

Purulent meningitis due to Rhodococcus equi. A case of posttraumatic infection.

Opportunistic infections due to Rhodococcus equi have been increasingly reported in the immunocompromised population, especially in patients with AIDS. In this report, we present an unusual case of purulent meningitis that developed in an immunocompetent six-year-old child through direct inoculation of R. equi.