Mariona Xercavins

Failure of Macrolide Antibiotic Treatment in Patients with Bacteremia Due to Erythromycin-Resistant Streptococcus pneumoniae

The rate of macrolide resistance among Streptococcus pneumoniae is increasing, but some investigators have questioned its clinical relevance. We conducted a matched case-control study of patients with bacteremic pneumococcal infection at 4 hospitals to determine whether development of breakthrough bacteremia during macrolide treatment was related to macrolide susceptibility of the pneumococcal isolate. Case patients (n=86) were patients who had pneumococcal bacteremia and an isolate that was either resistant or intermediately resistant to erythromycin. Controls (n=141) were patients matched for age, sex, location, and year that bacteremia developed who had an erythromycin-susceptible pneumococcus isolated. Excluding patients with meningitis, 18 (24%) of 76 case patients and none of 136 matched controls were taking a macrolide when blood was obtained for culture (P=.00000012). Moreover, 5 (24%) of 21 case patients with the low-level-resistant M phenotype and none of 40 controls were taking a macrolide (P=.00157). These data show that development of breakthrough bacteremia during macrolide or azalide therapy is more likely to occur among patients infected with an erythromycin-resistant pneumococcus, and they also indicate that in vitro macrolide resistance resulting from both the efflux and methylase mechanisms is clinically relevant.

Similarity between Human and Chicken Escherichia coli Isolates in Relation to Ciprofloxacin Resistance Status

BACKGROUND The food supply is suspected to be a source of fluoroquinolone-resistant Escherichia coli that cause disease in humans, but supporting molecular data are lacking. METHODS We performed a molecular-epidemiological comparison, in Barcelona, Spain (1996-1998), of 117 contemporaneous, geographically matched E. coli isolates from humans (35 blood isolates and 33 fecal) or chickens (49 fecal) that were either susceptible (n = 57) or resistant (n = 60) to ciprofloxacin and analyzed them by phylogenetic group, virulence genotype, and O antigens using random amplified polymorphic DNA (RAPD) analysis and pulsed-field gel electrophoresis (PFGE). RESULTS When analyzed by phylogenetic distribution, virulence profiles, and O antigens, resistant human isolates were distinct from susceptible human isolates but were largely indistinguishable from chicken isolates, whereas resistant and susceptible chicken isolates were similar. Susceptible human isolates contained more virulence-associated genes and more frequently expressed virulence-associated O antigens than did resistant human or any chicken isolates. Certain resistant human isolates closely resembled chicken isolates by RAPD and PFGE analysis. CONCLUSIONS Ciprofloxacin-resistant E. coli may arise de novo in poultry from susceptible progenitors, be transmitted to humans via the food supply, and go on to cause potentially life-threatening infections. If confirmed, these findings would mandate efforts to eliminate this reservoir of drug-resistant pathogens and/or to block their transmission to humans.

Urovirulence determinants in Escherichia coli strains causing prostatitis.

To define the urovirulence properties of Escherichia coli strains producing prostatitis, E. coli strains isolated from men with acute (7 strains) or chronic (23) prostatitis were compared with E. coli isolates from women with pyelonephritis (30), acute cystitis (60), or complicated urinary tract infection (UTI; 30). Strains from prostatitis patients were significantly more likely to express hemolysin than were strains causing complicated UTI (73% vs. 43%; P = .02) and more often demonstrated hybridization with the cytotoxic necrotizing factor-1 (CNF-1) probe (63%) than did strains from women (44%-48%). P fimbrial expression was highest among pyelonephritis (73%) and prostatitis strains (53%) and lowest among E. coli from women with complicated UTI (23%) and cystitis (30%; P < .05, prostatitis strains vs. either of the latter 2 groups). Results suggest that E. coli strains producing prostatitis generally possess urovirulence profiles similar to those of strains from women with acute uncomplicated pyelonephritis and that hemolysin and CNF-1 are especially prevalent in prostatitis strains.

Foodborne Nosocomial Outbreak of SHV1 and CTX-M-15–producing Klebsiella pneumoniae: Epidemiology and Control

BACKGROUND We describe a foodborne nosocomial outbreak due to extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae. METHODS An outbreak of ESBL K. pneumoniae was detected in March 2008. Initial control measures included contact isolation and a protocol for routine detection and reinforcement in hand hygiene practices. ESBL producers were screened for the bla(TEM), bla(SHV), and bla(CTX-M) genes. Pulsed-field gel electrophoresis analysis was performed using XbaI as a restriction endonuclease. RESULTS One hundred fifty-six colonized and/or infected patients were identified, 35 (22.4%) of whom had infection. The outbreak affected all hospital wards. Fecal carriage was up to 38% of patients in some wards. Of note, investigation revealed a very short delay between admission and colonization. None of the health care workers or environmental surfaces in the wards was found to be colonized. This prompted an epidemiological investigation of a possible foodborne transmission. We found that up to 35% of the hospital kitchen-screened surfaces or foodstuff were colonized and that 6 (14%) of 44 food handlers were found to be fecal carriers. Phenotypic and genotypic analysis of all clinical, environmental, and fecal carrier isolates showed the dissemination of a single strain of SHV-1 and CTX-M-15-producing K. pneumoniae. At that time, structural and functional reforms in the kitchen were performed. These were followed by a progressive reduction in colonization and infection rates among inpatients until complete control was obtained in December 2008. No restrictions in the use of antibiotics were needed. CONCLUSIONS To our knowledge, this is the first reported hospital outbreak that provides evidence that food can be a transmission vector for ESBL K. pneumoniae.

Ciprofloxacin prophylaxis in patients with acute leukemia and granulocytopenia in an area with a high prevalence of ciprofloxacin-resistant Escherichia coli.

Infection remains the major cause of morbidity and mortality in patients with neutropenia, and the beneficial effects of oral prophylaxis remain controversial.

Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study

BACKGROUND The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. METHODS In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0-7 [low mortality score] vs 8-15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. FINDINGS Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0-33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33-0·62]; p<0·0001). Among those receiving appropriate therapy, 135 (39%) received combination therapy and 208 (61%) received monotherapy. Overall mortality was not different between those receiving combination therapy or monotherapy (47 [35%] of 135 vs 85 [41%] of 208; adjusted HR 1·63 [95% CI 0·67-3·91]; p=0·28). However, combination therapy was associated with lower mortality than was monotherapy in the high-mortality-score stratum (30 [48%] of 63 vs 64 [62%] of 103; adjusted HR 0·56 [0·34-0·91]; p=0·02), but not in the low-mortality-score stratum (17 [24%] of 72 vs 21 [20%] of 105; adjusted odds ratio 1·21 [0·56-2·56]; p=0·62). INTERPRETATION Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to CPE. Combination therapy was associated with improved survival only in patients with a high mortality score. Patients with BSIs due to CPE should receive active therapy as soon as they are diagnosed, and monotherapy should be considered for those in the low-mortality-score stratum. FUNDING Spanish Network for Research in Infectious Diseases, European Development Regional Fund, Instituto de Salud Carlos III, and Innovative Medicines Initiative.

Seven-year review of bacteremia caused by Streptococcus milleri and other viridans streptococci.

TheStreptococcus milleri group is associated with a spectrum of serious suppurative infections that have not been well defined. The purposes of this study were to ascertain the clinical significance ofStreptococcus milleri bacteremia and to determine the epidemiological, clinical, and microbiological features of these infections compared to those caused by other viridans streptococci. All cases of streptococcal bacteremia observed in a Spanish hospital in the period from January 1988 to December 1994 were reviewed. Of 137 cases ofStreptococcus milleri infection, 33 (24%) were documented cases of bacteremia. Twenty-four patients were men (mean age 57.8 ± 17.4 years). The majority of infections were abdominal in origin (20/33), the most frequent diagnoses being cholangitis/cholecystitis (18%) and appendicitis (12%). The origin of infection could not be established in three cases. Nine cases of bacteremia (27%) were polymicrobial. Six patients (18%) had septic shock; in four the infection was polymicrobial, and in two the infection was of abdominal origin. Eighteen of the 33 patients (54%) required surgery. Five patients died. All 33Streptococcus milleri isolates were susceptible to penicillin. Twenty-two cases of bacteremia caused by other viridans streptococci were observed during the same period. There were no statistically significant differences between the two groups in terms of age, sex, mortality, rate of polymicrobial infection, rate of nosocomial acquisition of bacteremia, or the occurrence of shock. An abdominal origin of infection was more frequent inStreptococcus milleri bacteremia (p=0.0001); a cardiovascular origin was more frequent in the viridans group (p=0.01), as was a diagnosis of endocarditis (p=0.004). Four patients with viridans streptococci bacteremia required surgery versus 18 patients withStreptococcus milleri bacteremia (p=0.01). Viridans streptococci were notably less susceptible to penicillin (89%), clindamycin (79%), and erythromycin (79%).

Emergence of resistance to daptomycin in a cohort of patients with methicillin-resistant Staphylococcus aureus persistent bacteraemia treated with daptomycin

4 Theoretically estimated AUC 24 /MIC ratios against VRE susceptible to linezolid, according to the EUCAST clinical breakpoint (MIC¼ 4 mg/L), 1 were in the recommended range for the effective treatment of severe infections with linezolid (AUC 24 /MIC ratio of 80 –120) 6 in both cases (.93.76 and .250.96, respectively). In addition , biliary trough levels (C min) of linezolid were above the EUCAST clinical breakpoint against VRE in both cases (7.42 and 37.53 mg/L, respectively), this ensuring a theoretical T .MIC of .100%. The wide interindividual pharmacokinetic variability of linezolid observed between the two patients (patient 1: V ss 31. 5 L, CL 4.2 L/h and t 1/2 5.2 h; patient 2: V ss 67.1 L, CL 1.6 L/h and t 1/2 29.1 h) confirmed previous observations in critically ill patients during treatment with linezolid. 8 This variability is expected to potentially impact more on tolerability than on efficacy. Notably, patient 2 experienced hyperlactacidaemia (an increase in lactate level of 6.2 mmol/L during linezolid treatment), which could have been related to drug overexposure potentially favoured by drug –drug interactions and renal impairment. 8 However, it should not be overlooked that linezolid has generally been shown to be safe and effective in LTx patients. 9 The therapeutic drug monitoring of plasma C min may represent a valuable tool for the optimal management of linezolid in these cases, 8 and has recently been shown to improve safety outcomes in long-term treatment. 10 We recognize that the absence of real biliary pharmacokinetic/ pharmacodynamic data may be a limitation. However, these data confirm the potentially valuable role of linezolid in the treatment of cholangitis due to multidrug-resistant Enterococcus in LTx patients, since they meet the recommendations of good biliary penetration that are given in the Tokyo guidelines. References 1 Asín E, Isla A, Canut A et al. Comparison of antimicrobial pharmacokinetic/pharmacodynamic breakpoints with EUCAST and CLSI clinical breakpoints for Gram-positive bacteria. 4 Cremaschi E, Maggiore U, Maccari C et al. Linezolid levels in a patient with biliary tract sepsis, severe hepatic failure and acute kidney injury on sustained low-efficiency dialysis (SLED). 5 Pea F, Viale P, Lugano M et al. Biliary penetration and pharmacodynamic exposure of linezolid in liver transplant patients. 6 Rayner CR, Forrest A, Meagher AK et al. Clinical pharmacodynamics of linezolid in seriously ill patients treated in a compassionate use programme. 7 Pea F, Viale P, Lugano M et …

Hospital-Acquired Pneumococcal Bacteremia

To assess the most relevant features of hospital-acquired pneumococcal bacteremia, all cases of pneumococcal bacteremia at a single teaching hospital that occurred during 1988-2000 were prospectively studied. During this period, 374 cases of pneumococcal bacteremia were documented; 39 (10%) of these episodes were hospital acquired. Twenty-nine (74%) cases occurred during the period of December through May. Eleven (28%) of 39 patients had received antimicrobial agents in the month before the onset of bacteremia. All patients had underlying diseases that predisposed them to pneumococcal infection. The most common origin of infection was the respiratory tract, followed by the intra-abdominal region. Fifteen strains were fully susceptible to penicillin, and 20 were intermediately resistant. Only 25 strains were susceptible to erythromycin; all strains that were resistant to erythromycin were penicillin nonsusceptible. Eighteen (46%) of 39 patients died; the mortality rate related to infection was 39%.

Bacteraemic pneumococcal pneumonia in COPD patients: better outcomes than expected

The purpose of the study was to compare the clinical characteristics and outcomes of bacteraemic pneumococcal pneumonia (BPP) in chronic obstructive pulmonary disease (COPD) and non-COPD patients. A case-control study was conducted. Cases were any adult with BPP and forced expiratory volume in 1 second (FEV1) <80% and FEV1/forced expiratory vital capacity (FVC) <70%. Controls were patients with BPP without clinical diagnosis of COPD matched 1:2 by age, gender and date of isolation. Variables included co-morbidities, serotypes, pneumonia severity index (PSI), treatment and mortality. There were 45 cases and 90 controls. No significant differences were found in Charlson scores, antibiotic treatment, serotype distribution and severity. Malignancy, shock and mechanical ventilation were less frequent in COPD patients. One patient died vs 14 controls (p = 0.02). In univariate analysis, shock, multilobar involvement, Charlson score, heart failure and absence of COPD were associated with mortality. After adjustment for the presence of shock there were no differences in mortality. BPP presents less frequently with shock and has a lower mortality rate in COPD patients than in non-COPD patients.