The Role of AcrAB-TolC Efflux Pumps on Quinolone Resistance of E. coli ST131.

Escherichia coli ST131 is a cause for global concern because of its high multidrug resistance and several virulence factors. In this study, the contribution of acrAB-TolC efflux system of E. coli ST131 to fluoroquinolone resistance was evaluated. A total of nonrepetitive 111 ciprofloxacin-resistant E. coli isolates were included in the study. Multilocus sequence typing was used for genotyping. Expressions of acrA, acrB, and TolC efflux pump genes were measured by RT-PCR. Mutations in marA, gyrA, parC, and aac(6')-lb-cr positivity were studied by Sanger sequencing. Sixty-four (57.7%) of the isolates were classified as ST131, and 52 (81.3%) of the ST131 isolates belonged to H30-Rx subclone. In ST131, CTX-M 15 positivity (73%) and aac(6')-lb-cr carriage (75%) were significantly higher than those in non-ST131 (12.8% and 51%, respectively) (P < 0.05). The ampicillin-sulbactam (83%) resistance was higher, and gentamicin resistance (20%) was lower in ST131 than that in non-ST131 (64% and 55%, respectively) (P = 0.001 and P = 0.0002). Numbers of the isolates with MDR or XDR profiles did not differ in both groups. Multiple in-dels (up to 16) were recorded in all quinolone-resistant isolates. However, marA gene was more overexpressed in ST131 compared to that in non-ST131 (median 5.98 vs. 3.99; P = 0.0007). Belonging to H30-Rx subclone, isolation site, ciprofloxacin MIC values did not correlate with efflux pump expressions. In conclusion, the marA regulatory gene of AcrAB-TolC efflux pump system has a significant impact on quinolone resistance and progression to MDR profile in ST131 clone. Efflux pump inhibitors might be alternative drugs for the treatment of infections caused by E. coli ST131 if used synergistically in combination with antibiotics.

Rapid emergence of colistin resistance and its impact on fatality among healthcare-associated infections.

This article describes the emergence of resistance and predictors of fatality for 1556 cases of healthcare-associated Gram-negative bloodstream infection in 2014 and 2015. The colistin resistance rate in Klebsiella pneumoniae was 16.1%, compared with 6% in 2013. In total, 660 (42.4%) cases were fatal. The highest fatality rate was among patients with Acinetobacter baumannii bacteraemia (58%), followed by Pseudomonas aeruginosa (45%), Klebsiella pneumoniae (41%), Enterobacter cloacae (32%) and Escherichia coli (28%). On multi-variate analysis, the minimum inhibitory concentrations for carbapenems [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01-1.04; P = 0.002] and colistin (OR 1.1, 95% CI 1.03-1.17; P = 0.001) were found to be significantly associated with fatality.

Healthcare-associated Gram-negative bloodstream infections: antibiotic resistance and predictors of mortality.

This article describes the prevalence of antibiotic resistance and predictors of mortality for healthcare-associated (HA) Gram-negative bloodstream infections (GN-BSI). In total, 831 cases of HA GN-BSI from 17 intensive care units in different centres in Turkey were included; the all-cause mortality rate was 44%. Carbapenem resistance in Klebsiella pneumoniae was 38%, and the colistin resistance rate was 6%. Multi-variate analysis showed that age >70 years [odds ratio (OR) 2, 95% confidence interval (CI) 1.22-3.51], central venous catheter use (OR 2.1, 95% CI 1.09-4.07), ventilator-associated pneumonia (OR 1.9, 95% CI 1.1-3.16), carbapenem resistance (OR 1.8, 95% CI 1.11-2.95) and APACHE II score (OR 1.1, 95% CI 1.07-1.13) were significantly associated with mortality.

Antimicrobial susceptibilities of uropathogen Escherichia coli in renal transplant recipients: dramatic increase in ciprofloxacin resistance.

The urinary tract is the most common site of bacterial infections in renal transplant recipients. The management of urinary tract infections (UTI) in renal transplant recipients is becoming more difficult because of drug-resistant bacteria. The antimicrobial susceptibilities of uropathogen bacteria isolated from 398 patients who underwent renal transplantation between 2007 and 2011 were obtained from medical records. At least 1 UTI episode was diagnosed in 172 (43.2%) patients. Among the 703 bacteria isolated from these patients, Exherichia coli the most common pathogen, was isolated from 407/703 episodes (57.8%). Ciprofloxacin, co-trimoxazole, ceftriaxone, and gentamicin resistance rates were 59.4%, 85.7%, 40.7%, and 36.6%, respectively. Ninty six of 407 E. coli isolates (23.5%) were ESBL positive. Analysis of resistance rates in our center demonstrated ciprofloxacin resistance rate in uropathogenic E. coli to have increased gradually from 30.4% in 2003, 41.3% in 2007, and 59.4% in 2012. Instutional data regarding the etiologic agents and antimicrobial susceptibility results are important for proper management of patients with UTI.

Risk factors for extended-spectrum beta-lactamase positivity in uropathogenic Escherichia coli isolated from community-acquired urinary tract infections.

The aim of this prospective cohort study was to determine the risk factors for community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-positive Escherichia coli and the distribution of the ESBL enzyme types. Structured forms were filled in for patients diagnosed with community-acquired UTI in four different geographical locations in Turkey. The forms and the isolates were sent to the central laboratory at Baskent University Hospital, Ankara. Antimicrobial susceptibility was determined according to the CLSI criteria. PCR and DNA sequencing were used to characterize the bla(TEM), bla(CTX-M) and bla(SHV) genes. Multivariate analysis was performed using logistic regression. A total of 510 patients with UTI caused by Gram-negative bacteria were included in this study. ESBLs were detected in 17 of 269 (6.3%) uropathogenic E. coli isolates from uncomplicated UTIs and 34 of 195 (17.4%) E. coli isolates from complicated UTIs (p <0.001). According to multivariate analysis, more than three urinary tract infection episodes in the preceding year (OR 3.8, 95% CI 1.8-8.1, p <0.001), use of a beta-lactam antibiotic in the preceding 3 months (OR 4.6, 95% CI 2.0-0.7, p <0.001) and prostatic disease (OR 9.6, 95% CI 2.1-44.8, p 0.004) were found to be associated with ESBL positivity. The percentages of isolates with simultaneous resistance to trimethoprim-sulphamethoxazole, ciprofloxacin and gentamicin were found to be 4.6% in the ESBL-negative group and 39.2% in the ESBL-positive group (p <0.001). Forty-six of 51 ESBL-positive isolates (90.2%) were found to harbour CTX-M-15. Therapeutic alternatives for UTI, particularly in outpatients, are limited. Further clinical studies are needed to guide the clinicians in the management of community-acquired UTIs.

Prevalence of cutaneous bacterial infections and nasal carriage of Staphylococcus aureus in recipients of renal transplants.

BACKGROUND: Renal transplant recipients (RTRs) often develop bacterial infections as a result of their long-term immunosuppressive treatment. However, there is no published case-control study of cutaneous bacterial infections in this population, and the prevalence of nasal Staphyloccus aureus carriage and its role in cutaneous bacterial infections in RTRs are not known. AIMS: To determine whether the prevalence of cutaneous bacterial infections and nasal S. aureus carriage are increased in RTRs and to investigate the association between nasal S. aureus carriage and cutaneous staphylococcal infections. METHODS: In total, 66 outpatient RTRs and 67 controls were investigated for the presence of cutaneous bacterial infections. Bacterial cultures were taken from clinically suspicious cutaneous lesions, and three nasal swabs were collected to detect nasal S. aureus colonization. RESULTS: Cutaneous bacterial infection was suspected in 42.4% of RTRs, and in 14.2% of controls. However, of the lesions that could be cultured, microbiologically proven cutaneous bacterial [methicillin-sensitive S. aureus (MSSA)] infections were confirmed in only two RTRs and one control subject. Nasal S. aureus carriage was found in 10.6% of RTRs and 29.9% of controls (P < 0.05). Both RTRs with MSSA infection were nasal carriers, whereas nasal S. aureus carriage was not detected in the only control subject with MSSA infection. All S. aureus isolates were oxacillin-sensitive. CONCLUSION: Screening for nasal S. aureus carriage does not seem to assist in preventing staphylococcal bacterial infections in outpatient RTRs.

In vitro activity of tigecycline against resistant micro-organisms isolated from burn patients.

Infections in burn patients are usually caused by multidrug-resistant micro-organisms. Tigecycline, a derivative of glycylcyclines, is an effective antibiotic against the resistant strains. The aim of this study is to determine the in vitro activity of tigecycline against the multidrug-resistant bacteria isolated from burn patients. Fourty-seven bacteria isolated from 118 patients hospitalized in the burn unit during 2003-2006 were included in the study. Gram-negative bacteria that were resistant to at least six broad-spectrum antibiotics, methicillin-resistant staphylococci and ampicillin-resistant enterococci were studied. Minimal inhibitory concentration values of tigecycline against these bacteria were tested by E-test strips. Susceptibility breakpoints were determined according to the previous studies;

Urinary tract infections in renal transplant recipients.

Urinary tract infection (UTI) is the most common infectious complication following renal transplantation. The purposes of this study were to determine the causative agents of UTIs among renal transplant recipients and to compare the antibiotic susceptibilities of Escherichia coli strains isolated from renal transplant recipients and complicated community-acquired UTIs. We evaluated 75 episodes of 63 recipients with confirmed UTI who underwent transplantation during the period 1981 to 2006 at our center. Medical records of the patients were reviewed retrospectively. To compare the susceptibility rates of E coli, 226 isolates from nontransplant patients with complicated community-acquired UTIs were also evaluated. Ten episodes (13.3%) occurred in the first month following the transplantation, 11 (14.7%) in the period of the second month to the sixth month, and 54 (72%) after the sixth month of transplantation. Forty-six (61.3%) isolates were E coli. Among these isolates, ciprofloxacin resistance rates were 50% (2/4) in the first month after transplantation, 75% (6/8) in the period of the second month to the sixth month, and 32.4% (11/34) beyond 6 months after transplantation. The resistance rates of trimethoprim/sulfamethoxazole (TMP-SMX) in the same time periods were 100% (4/4), 87.5% (7/8), and 70.6% (24/34), respectively. The rates of resistance to TMP-SMX among E coli isolated from renal recipients were significantly higher than those in community-acquired complicated UTIs. The increased resistance of urinary pathogens to this agent is a major concern. Although high resistance rates of ciprofloxacin against E coli strains were determined in this group, it was not found to be statistically significant.

Etiologic agents of diarrhea in solid organ recipients.

After transplantation, diarrhea may be caused by infectious agents, drug-specific effects, metabolic conditions, or mechanical complications of surgery. Determining the cause helps to determine whether to initiate antimicrobial therapy and the duration of treatment. In this study we aimed to determine the causes of diarrhea in kidney or liver recipients. Fifty-two diarrhea episodes among 43 solid organ recipients were evaluated. The cause of diarrhea was detected in 43 patients (82.6%). Infectious etiologies accounted for 33 out of the 43 episodes (76.7%) in which a specific cause was determined: Giardia lamblia in 9, Cryptosporidium parvum in 7, cytomegalovirus (CMV) in 6, Clostridium difficile in 3, Campylobacter jejuni in 2, Shigella sonnei in 2, Salmonella enteritidis in 1, rotavirus in 1, Entamoeba histolytica in 1, and Blastocystis hominis in 1. Non-infectious etiologies were found for 10 episodes (23.3%): mycophenolate mofetil-associated diarrhea in 5, antibiotic-associated diarrhea in 2, colchicine-associated diarrhea in 2, and laxative drug-associated in 1. Non-infectious etiologies seem to be relatively common causes of diarrhea among transplant recipients. Therapy was adjusted in 5 patients because of mycophenolate mofetil-associated diarrhea. CMV and C. parvum, which are seldom seen in the normal population, were frequent causes of diarrhea in this group. Evaluating the transplant recipients for non-infectious causes of diarrhea is important in prompt diagnosis and treatment.

Opportunistic posterior uveal infections in renal transplant patients.

AIMS: To describe the cases of opportunistic posterior uveal infection diagnosed in renal transplant recipients at a single center over a 10-year period. METHODS: The study involved 1156 patients who underwent renal transplantation. Five of the recipients were diagnosed with posterior uveal infection. The specific diagnoses were acute retinal necrosis (two cases), cytomegalovirus retinitis (one case), nocardial chorioretinitis (one case), or tuberculoid granuloma (one case). RESULTS: The five patients were aged 27 to 55 years, and the interval from renal transplantation to uveal infection ranged from 7 months to 16 years. All patients were receiving immunosuppressive treatment at the time of the posterior uveal infection. Acute retinal necrosis was diagnosed in cases I and II at 2 and 3 years after transplantation, respectively. In both cases, fundus examination revealed moderate vitritis and yellow-white lesions representing confluent retinitis. In case III (cytomegalovirus retinitis), 7 months after transplantation the patient developed extensive hemorrhage and confluent white exudates, periphlebitis, and perivascular sheathing in the right eye. In case IV, culture of a fine-needle aspirate from a well-demarcated, white-yellow, elevated choroidal lesion in the superotemporal region of the macula revealed nocardial infection. Fundus examination of the right eye of case V revealed a small, hypopigmented choroidal lesion superior to the optic disc. The lesion was identified as a choroidal tuberculoid granuloma. CONCLUSIONS: Opportunistic chorioretinal infections can occur at any time after renal transplantation. So it is important that every kidney recipient undergo regular ophthalmic examinations throughout his or her lifetime.

Value of automatized blood culture systems in the diagnosis of continuous ambulatory peritoneal dialysis peritonitis.

Peritonitis is a common clinical problem that occurs in patients with end-stage renal disease treated by peritoneal dialysis. The aim of this study was to evaluate the value of blood culture systems for the diagnosis of continuous ambulatory peritoneal dialysis (CAPD) peritonitis among 26 samples of peritoneal fluid obtained from patients with the suspicion of CAPD peritonitis. Significant growth was detected in 12 (70.5%) of 17 bacteria-positive samples. The most striking finding was that 8 (66.6%) of these 12 results were obtained only from blood culture bottles. The identified pathogens were methicillin-sensitive coagulase-negative staphylococci (n = 5), alpha-hemolytic streptococci (n = 2), Corynebacterium spp. (n = 2), Escherichia coli (n = 2), and Enterococcus faecalis (n = 1). Using blood culture bottles inoculated with peritoneal fluid at the bedside, rather than submitting the specimen to the laboratory for later processing, is advocated in the prompt diagnosis of CAPD peritonitis.

Incidence of inducible clindamycin resistance in staphylococci: first results from Turkey.

In total, 408 staphylococcal isolates were tested for inducible clindamycin resistance (ICR) by the disk-diffusion induction test (D-test). ICR was detected in 5.7% of 105 methicillin-resistant Staphylococcus aureus (MRSA) isolates, 3.6% of 111 methicillin-susceptible S. aureus isolates, 30.8% of 94 methicillin-resistant coagulase-negative staphylococcal (CoNS) isolates, and 11.2% of 98 methicillin-sensitive CoNS isolates. All MRSA isolates that were erythromycin-resistant and clindamycin-susceptible were positive by the D-test. The same results were obtained with an azithromycin instead of an erythromycin disk. All isolates were susceptible to quinupristin-dalfopristin. The cost-benefit of the d-test should be evaluated locally after determining the incidence of the different resistance phenotypes.