Alper Tünger

Comparative activity of carbapenem testing: the COMPACT study

OBJECTIVES Doripenem is a new carbapenem recently introduced into Europe. The COMParative Activity of Carbapenem Testing (COMPACT) study compared the susceptibility of common Gram-negative bacilli causing serious infections in hospitalized patients with doripenem, imipenem and meropenem. METHODS Gram-negative isolates (4498 total: 2171 Pseudomonas species; 1910 Enterobacteriaceae; and 417 other Gram-negative bacilli) were collected from 80 centres in 16 countries in Europe, the Middle East and Africa during 2008-09. The MICs of doripenem, imipenem and meropenem were determined using Etest methodology and broth microdilution. Susceptibility was interpreted according to CLSI, EUCAST and FDA breakpoints. RESULTS The MIC(90)s of doripenem, imipenem and meropenem for all isolates were 8, ≥64 and 32 mg/L, respectively. Doripenem had the lowest MIC(90) for Pseudomonas species at 16 mg/L, with imipenem and meropenem values of ≥64 mg/L. Enterobacteriaceae were highly susceptible to all three carbapenems, with MIC(90)s of doripenem, imipenem and meropenem of 0.06, 0.5 and 0.12 mg/L, respectively. Other Gram-negative isolates, predominantly Acinetobacter baumannii, were resistant to all three carbapenems (MIC(90) ≥64 mg/L). Susceptibility to doripenem was observed in 14.9% of isolates resistant to imipenem and/or meropenem. CONCLUSIONS Doripenem showed excellent activity against Gram-negative isolates; generally it was more active than imipenem and at least as good as meropenem. Against Pseudomonas species, doripenem was more active than both imipenem and meropenem, with doripenem susceptibility observed for some imipenem- and/or meropenem-resistant isolates.

Comamonas testosteroni meningitis in a patient with recurrent cholesteatoma

Comamonas testosteroni, a lesser‐known member of the genus, has shown little apparent capacity for causing infections in humans. We here present a case of purulent meningitis due to C. testosteroni, which occurred in a patient who had recurrent cholesteatoma. Ceftriaxone treatment was not effective in this patient even though in vitro the bacteria were susceptible to the drug. The patient responded well to meropenem therapy.

In vitro activities of various antimicrobials against Brucella melitensis strains in the Aegean region in Turkey.

Objective: To study in vitro activities of three quinolones (ciprofloxacin, levofloxacin, moxifloxacin), four macrolides (erythromycin, dirithromycin, azithromycin, clarithromycin) and doxycycline against 44 clinical isolates of Brucella melitensis. Materials and Methods: Forty-four B. melitensis strains were isolated from blood cultures of adult patients with acute brucellosis who were hospitalized in the clinical ward of the Department of Clinical Microbiology and Infectious Diseases. The minimum inhibitory concentrations (MICs) of the tested antimicrobials were measured by the agar dilution method. MIC90 and MIC50 values were defined as the lowest concentration of the antibiotic at which 90 and 50% of the isolates were inhibited, respectively. Results: Doxycycline (MIC50: 0.25 µg/ml, MIC90: 0.50 µg/ml) had the lowest MIC in vitro against the B. melitensis strains. Among the quinolones, ciprofloxacin and levofloxacin had similar activities (MIC50: 0.5 µg/ml, MIC90: 2 µg/ml), whereas MIC of moxifloxacin (MIC50: 1 µg/ml, MIC90: 8 µg/ml) was higher than both antibiotics in this group. Clarithromycin and azithromycin were the most active macrolides (MIC50: 8 µg/ml and MIC90: 32 µg/ml), followed by erythromycin (MIC50: 16 µg/ml, MIC90: 32 µg/ml) and dirithromycin (MIC50: 64 µg/ml and MIC90: 64 µg/ml). Conclusion: The results indicate that the conventional agent doxycycline is more active than quinolones and macrolides against the B. melitensis in vitro.

Risk factors for microbial contamination of peripheral blood stem cell products.

BACKGROUND: Despite the well‐known contamination rates and presence of microbial agents in stem cell products, the risk factors affecting microbial contamination have not been well described.

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.

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 β-lactamase positive while 9.1% were β-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.

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 coagulasenegative 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.

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.

Nasal Staphylococcus aureus carriage is not increased in Behçet’s disease

Sir In the context of a susceptible genetic background, infectious agents are believed to play a role in the pathogenesis of Behçet’s disease (BD), which is a systemic vasculitis, first defined in 1937 as a triad of oral aphtae, genital ulcerations and iridocyclitis [1, 2]. Streptococci are among the infectious agents suggested as playing a role in BD, based upon clinical observations such as increased oral manifestations after dental treatment, hypersensitivity to streptococcal skin tests, dominance of atypical streptococcal species in patients with the oral flora of BD, and recent reports of beneficial antibacterial treatment [1]. Unlike streptococci, the literature data about the staphylococci and BD are scarce. In vitro, abnormal T cell responses to Staphylococcus aureus superantigens have been shown in BD [3], and a Behçet’s patient was reported in whom disease activity was exacerbated due to staphylococcal gingival infection [4]. Exacerbation included not only the oral ulcers, but also the genital ulcers and skin lesions, and eradication resulted in complete recovery [4]. On the other hand, the relationship between nasal S. aureus (S. aureus) carriage and Wegener granulomatosus (WG), which is also a systemic vasculitis, is well known [5]. We therefore aimed to search for a possible relationship between staphylococci and BD, and tried to answer two basic questions: (1) is the frequency of nasal S. aureus carriage in Behçet’s patients more frequent than in healthy controls? and (2) are there significant differences between Behçet’s patients with and without nasal carriage of S. aureus with respect to various disease parameters. Unlike in the case of WG, nasal ulcers are not seen in BD. However, since the nose is known to be a frequent site of staphylococcal colonization, and nasal colonization has tended to correlate with colonization at other sites [6], we preferred to investigate nasal carriage of S. aureus. We studied 45 consecutive Behçet’s patients (M/ F: 23/22, mean age 42.2±10.9 years, mean disease duration 10.0±6.2 years) being followed up by the Ege University Rheumatology Department, and fulfilling the International Study Group criteria [7]. Due to the lack of a sufficient number of WG patients, we could not constitute a positive control group of WG patients. The healthy control group consisted of 20 cases which were ageand sex-matched with the Behçet’s group. All the participants provided informed consent. Exclusion criteria were hospitalization during the last 6 months, antibiotic treatment during the last month or being a member of hospital staff. Since immunosuppressive treatment may affect nasal S. aureus colonization, the patients were also questioned about their current medication. Nasal swab specimens were taken three times with at least 10-day intervals, using sterile swabs. The swabs were immediately placed in Stuart’s transport medium. They were inocculated to 5% sheep blood agar medium and incubated at 35 C for 24 h. Then the grown bacteria were identified by conventional microbiological tests [6]. Fisher exact test and the Mann–Whitney U test were used for statistical analysis. A P value less than 0.05 was accepted as significant. The frequency of nasal S. aureus colonization in Behçet’s patients (15/45; 33%) was considerably higher than in healthy controls (4/20; 20%), but there was no significant difference between the groups. These figures were compatible with the reported nasal S. aureus carriage rate in adults, ranging from 20% to 40%, depending on seasonal and local epidemiological factors [6]. Behçet’s patients with nasal carriage of S. aureus showed no difference to those without, with respect to G. Keser (&) Æ K. Aksu Æ E. Doganavsargil Department of Rheumatology, Ege University Medical School, Mithatpasa cad. No: 772/18, Nallıoglu apt, 35280 Izmir, Turkey E-mail: agkkeser@hotmail.com Fax: +90-232-3423289

Investigation of the Antimicrobial Susceptibility Profile, Virulence Genes, and Epidemiologic Relationship of Clinical Salmonella Isolates

Objectives: The objectives of this study were to investigate the epidemiologic relationship, prevalence of the beta-lactamase and virulence genes of clinical ampicillin-resistant Salmonella enterica. Materials and Methods: In vitro ampicillin susceptibilities of 117 Salmonella enterica isolates obtained between 2011-2012 from Ege University Hospital, Bacteriology Laboratory of Medical Microbiology Department were examined using disc diffusion assays in accordance with the CLSI guidelines. The MIC levels in the ampicillin-resistant bacteria were determined using the broth microdilution method. The resistant strains were serotyped by the Public Health Institution. Epidemiologic relations of resistant strains were evaluated using ERIC-PCR. The presence of beta-lactamase genes and virulence factors were detected using PCR. Results: The 117 S. enterica strains had ten isolates that were resistant to ampicillin, and the MIC range of ampicillin was found as 512-128 μg/mL. Ampicillin-resistant strains were susceptible to nalidixic acid, ciprofloxacin, cefotaxime, sulfamethoxazole/trimethoprim. Four different serotypes were identified and isolates were grouped into seven clusters. Five isolates carried blaTEM, and two carried the blaCTX-M gene. However, it was determined that blaSHV and blaPER genes did not exist in these strains. Virulence genes invA, pipD, and sopB were found in all isolates. sifA, pefA, and sopE genes were found in seven, four, and three isolates, respectively. Conclusion: Our data suggest that the rate of ampicillin resistance in S. enterica isolates was 8.5% in the two year period, but this ratio was generally lower than rates abroad. blaCTX-M and blaTEM genes could be responsible for ampicillin resistance. The blaSHV gene, which is highly prevalent in our country, was not found in any strains. sopB and pipD genes, which might be associated with beta-lactam resistance, were found in all strains. It is also noteworthy that the three isolates containing the sopE gene, which is associated with epidemic cases, were of the same serotypes and epidemiologic clusters.