Diagnosis and treatment of catheter-related bloodstream infection: Clinical guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology and (SEIMC) and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC).

Catheter-related bloodstream infections (CRBSI) constitute an important cause of hospital-acquired infection associated with morbidity, mortality, and cost. The aim of these guidelines is to provide updated recommendations for the diagnosis and management of CRBSI in adults. Prevention of CRBSI is excluded. Experts in the field were designated by the two participating Societies (the Spanish Society of Infectious Diseases and Clinical Microbiology and [SEIMC] and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units [SEMICYUC]). Short-term peripheral venous catheters, non-tunneled and long-term central venous catheters, tunneled catheters and hemodialysis catheters are covered by these guidelines. The panel identified 39 key topics that were formulated in accordance with the PICO format. The strength of the recommendations and quality of the evidence were graded in accordance with ESCMID guidelines. Recommendations are made for the diagnosis of CRBSI with and without catheter removal and of tunnel infection. The document establishes the clinical situations in which a conservative diagnosis of CRBSI (diagnosis without catheter removal) is feasible. Recommendations are also made regarding empirical therapy, pathogen-specific treatment (coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus spp., Gram-negative bacilli, and Candida spp.), antibiotic lock therapy, diagnosis and management of suppurative thrombophlebitis and local complications.

Pathogen-related factors affecting outcome of catheter-related bacteremia due to methicillin-susceptible Staphylococcus aureus in a Spanish multicenter study.

Even with appropriate clinical management, complicated methicillin-susceptible Staphylococcus aureus (MSSA) catheter-related bacteremia (CRB) is frequent. We investigated the influence of molecular characteristics of MSSA strains on the risk of complicated bacteremia (CB) in MSSA-CRB. A multicenter prospective study was conducted in Spain between 2011 and 2014 on MSSA-CRB. Optimized protocol-guided clinical management was required. CB included endocarditis, septic thrombophlebitis, persistent bacteremia and/or end-organ hematogenous spread. Molecular typing, agr functionality and DNA microarray analysis of virulence factors were performed in all MSSA isolates. Out of 83 MSSA-CRB episodes included, 26 (31.3%) developed CB. MSSA isolates belonged to 16 clonal complexes (CCs), with CC30 (32.5%), CC5 (15.7%) and CC45 (13.3) being the most common. Comparison between MSSA isolates in episodes with or without CB revealed no differences regarding agr type and functionality. However, our results showed that CC15 and the presence of genes like cna, chp and cap8 were associated with the development of CB. The multivariate analysis highlighted that the presence of cna (Hazard ratio 2.9; 95% CI 1.14-7.6) was associated with the development of CB. Our results suggest that particular CCs and specific genes may influence the outcome of MSSA-CRB.

Is reduced vancomycin susceptibility a factor associated with poor prognosis in MSSA bacteraemia?

OBJECTIVES: The known data about the influence of vancomycin MIC on Staphylococcus aureus bacteraemia are contradictory. Our objective was to study the possible impact of vancomycin MIC ≥1.5 mg/L on short- and medium-term mortality. METHODS: A prospective cohort study was carried out from March 2008 to January 2011 on adult patients with MSSA bacteraemia admitted to a tertiary hospital located in Seville (Spain). We studied the relationship between vancomycin MIC, accessory gene regulator (agr) type and absence of δ-haemolysin and poor prognosis. All isolates were genotyped by PFGE. Multivariate analysis, including a propensity score for having a vancomycin MIC of ≥1.5 mg/L, was performed by Cox regression. RESULTS: One hundred and thirty-five episodes of bacteraemia due to MSSA were included in the analysis. Twenty-nine (21.5%) isolates had a vancomycin MIC of ≥1.5 mg/L by Etest. There were no differences in agr distribution or absence of δ-haemolysin between isolates with reduced vancomycin susceptibility (RVS) and those without. RVS was not more frequent in specific clones; RVS was not associated with higher 14 or 30 day crude mortality (relative risk = 0.44, 95% CI = 0.14-1.35; and relative risk = 1.01, 95% CI = 0.52-1.96) rates, and it did not show higher rates of complicated bacteraemia (14.2% versus 13.8%, P = 0.61). Cox regression analysis did not significantly modify the results for 14 day mortality (HR = 0.39, 95% CI = 0.11-1.34) or 30 day mortality (HR = 0.89, 95% CI = 0.39-2.04). CONCLUSIONS: Contrary to previously published data, we did not find a relationship between RVS and higher mortality in patients with MSSA bacteraemia and we did not find a link with higher complicated bacteraemia rates.

Clinical and molecular epidemiology of meticillin-resistant Staphylococcus aureus causing bacteraemia in Southern Spain.

BACKGROUND: Some molecular features of meticillin-resistant Staphylococcus aureus (MRSA) isolates causing invasive infections have been shown to have clinical implications. There is a need to monitor the situation using a combination of molecular and clinical data because, although MRSA clones tend to predominate over wide geographical areas, clonal shifts may take place. AIM: To study the epidemiological features and perform molecular characterization of a retrospective cohort of 98 cases of nosocomial and healthcare-associated MRSA bacteraemia in 10 hospitals in Andalusia, Spain. METHODS: Relatedness of isolates was investigated using pulsed-field gel electrophoresis (PFGE), S. aureus protein A (spa) typing and clonal complex (CC) assignment. Staphylococcal chromosomal cassette mec (SCCmec) type and accessory gene regulator (agr) group were studied by polymerase chain reaction. agr function was assessed. RESULTS: Most isolates were CC5, SCCmec type IV and agr group II. The most common spa type was t067. Six major clusters were identified by PFGE. Six small clusters of epidemiologically related cases sharing isolates from the same PFGE subtype were identified. Five percent of isolates had a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL on broth microdilution, although 44% had an MIC >1 µg/mL on E-test. Variables independently associated with MIC >1 mg/L on E-test were surgery during present admission and Charlson index ≥2. CONCLUSION: A specific CC that has been predominant in Spain over the last decade caused most of the cases in this study. PFGE was more discriminatory than spa typing in showing clusters of epidemiologically related cases. Some patient features were associated with vancomycin MIC >1 mg/L on E-test.

Fatal levofloxacin failure in treatment of a bacteremic patient infected with Streptococcus pneumoniae with a preexisting parC mutation.

The fatal outcome of levofloxacin treatment in a patient with bacteremic pneumonia caused by Streptococcus pneumoniae with a preexisting parC mutation is reported. Failure was due to the emergence of a gyrA mutation after 4 days of therapy. Problems encountered in detecting first-step mutation isolates are discussed.

In vitro activity of fosfomycin against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: comparison of susceptibility testing procedures.

The agar dilution, broth microdilution, and disk diffusion methods were compared to determine the in vitro susceptibility of 428 extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin. Fosfomycin showed very high activity against all ESBL-producing strains. Excellent agreement between the three susceptibility methods was found for E. coli, whereas marked discrepancies were observed for K. pneumoniae.

Activity of cefepime and carbapenems in experimental pneumonia caused by porin-deficient Klebsiella pneumoniae producing FOX-5 beta-lactamase.

The in-vivo activities of cefepime, imipenem and meropenem against the porin-deficient strain Klebsiella pneumoniae C2 and its derivative K. pneumoniae C2(pMG252) coding for the AmpC-type beta-lactamase FOX-5 were determined. Bactericidal activities were determined with the kill-curve method. A pneumonia model in guinea-pigs was developed, and Cmax, t(1/2) and DeltaT/MIC were calculated for the three agents tested. Animals were treated for 72 h with sterile saline (control group) or with cefepime, imipenem or meropenem (240 mg/kg/day, intramuscularly, three times daily). Bacterial counts in lungs (log10 CFU/g tissue) were determined by serial dilution. MICs (mg/L) of cefepime, imipenem and meropenem against K. pneumoniae C2/K. pneumoniae C2(pMG252), determined by macrodilution, were: 0.5/4, 0.5/0.5 and 0.25/0.5, respectively. Bacterial counts in the lungs of animals infected with K. pneumoniae C2 and treated with antimicrobial agents were always lower than in the control group (cefepime, 4.4 +/- 0.5; imipenem, 4.6 +/- 0.4; meropenem, 4.7 +/- 0.5; control group, 5.6 +/- 0.8; p <0.01). No significant differences were observed among the groups receiving therapy (p >0.05). Bacterial lung clearance was higher in treated animals than in control animals following infection with K. pneumoniae C2(pMG252) (cefepime, 4.5 +/- 0.4; imipenem, 4.0 +/- 0.3; meropenem, 4.6 +/- 0.4; control group, 6.1 +/- 0.6; p <0.01), with imipenem producing better clearance than either cefepime or meropenem (p <0.05). Thus, in the guinea-pig pneumonia model, cefepime, imipenem and meropenem were each effective against the porin-deficient K. pneumoniae strain C2 and its derivative expressing the plasmid-mediated AmpC type beta-lactamase FOX-5.

Evaluation of the WIDER I system for antimicrobial susceptibility testing of clinical isolates of Haemophilus influenzae and Streptococcus pneumoniae.

The aim of this study was to evaluate the WIDER I system for susceptibility testing of Haemophilus influenzae and Streptococcus pneumoniae. MICs of 12 antimicrobials against 42 H. influenzae and 58 S. pneumoniae strains were determined using 1W MIC panels and compared with those obtained by microdilution. Overall essential agreements were >99%. Very major errors were not detected. Major errors occurred with ampicillin (1.7% H. influenzae). Minor errors were 2.3% (amoxicillin-clavulanate, cefuroxime, chloramphenicol), 7.1% (ampicillin) and 16.7% (clarithromycin) for H. influenzae, and 1.7% (chloramphenicol, erythromycin, meropenem), 3.4% (amoxicillin-clavulanate, cefuroxime, tetracycline) and 8.6% (levofloxacin) for S. pneumoniae. The WIDER I system is a reliable method for susceptibility testing of H. influenzae and S. pneumoniae.

Timing of intrapartum ampicillin and prevention of vertical transmission of group B streptococcus.

OBJECTIVE: To evaluate the relationship between the time elapsed from the administration of ampicillin prophylaxis to delivery and its efficacy in interrupting intrapartum transmission of group B streptococcus. METHODS: During the 12-month study period, all women who came to the Virgen de las Nieves Hospital (Granada, Spain) for delivery were screened for group B streptococcus vaginal carriage by a pigment-detection culture-based procedure. Colonized women were treated with ampicillin (2 g intravenously), and the interval between ampicillin administration and delivery was recorded. Newborns from colonized mothers also were screened to detect group B streptococcus colonization. RESULTS: During the study period, 4525 women were admitted to the hospital for delivery and screened for group B streptococcus vaginal colonization. Group B streptococcus was detected in 543 women (12%), of whom 454 gave birth vaginally to 454 liveborn infants. Intrapartum ampicillin was given to 201 of these 454 women (44%), and 10% of the newborns from mothers who received intrapartum ampicillin prophylaxis were colonized by group B streptococcus. The relationship between timing of ampicillin administration and rate of neonatal group B streptococcal transmission was as follows: less than 1 hour before delivery, 46%; 1-2 hours, 29%; 2-4 hours, 2.9%; and more than 4 hours, 1.2%. Among the 253 mothers who received no intrapartum prophylaxis, colonization was found in 120 of their newborns (47%). CONCLUSION: When the time between the start of ampicillin prophylaxis and delivery is at least 2 hours, vertical transmission of group B streptococcus is minimized.

Nontyphoidal salmonella intracranial infections in HIV-infected patients.

Salmonella focal intracranial infections are unusual in human immunodeficiency virus (HIV)-infected patients. Six such infections have been reported in the world literature. We report a case of salmonella subdural and epidural cerebral empyema with concomitant osteomyelitis of the frontal bone. Such a complication in the course of salmonellosis is reported for the first time. In previously published case reports, four patients had brain abscess and two had subdural empyema. Salmonella typhimurium was isolated from two patients, and different serotypes were recovered from the others. All patients had advanced HIV disease, and all but two had had opportunistic infections before the diagnosis of salmonella intracranial infection. Surgical drainage combined with systemic antibiotic therapy resulted in the recovery of four of five patients. No regression of the lesions occurred in one patient treated only with antibiotics for multiple cerebral abscesses.

Efficacy of a universal screening program for the prevention of neonatal group B streptococcal disease.

Universal antepartum vaginal cultures for group B streptococcus (GBS) were initiated in a Spanish hospital in 1994 using Granada medium. Infants born to carriers were monitored closely, and blood, urine and mucocutaneous areas were cultured for GBS. Group B streptococcus was detected in 543 of 4,525 women (12%). Of these, 454 gave birth vaginally, of whom 201 (44%) received intrapartum ampicillin. Prophylaxis was not administered to 253 women (56%). In this group, infants of 120 women were colonized and 1 case of neonatal GBS disease occurred. Using this protocol, most GBS carriers with risk factors received intrapartum prophylaxis. This protocol also led to early identification of colonized newborns.

Prospective evaluation of a two-week course of intravenous antibiotics in intravenous drug addicts with infective endocarditis. Grupo de Estudio de Enfermedades Infecciosas de la Provincia de Cádiz.

In a prospective study, a two-week course of antibiotics (cloxacillin 2 g/4 h plus amikacin 7.5 mg/kg/12 h) was evaluated in the therapy of right-sided infective endocarditis in intravenous drug users (IVDU). All IVDU admitted to hospital during the study period who fulfilled the strict criteria for diagnosis of infective endocarditis were analysed. A subgroup of patients with right-sided endocarditis caused by Staphylococcus aureus who had a good prognosis were selected as being eligible for the two-week course of treatment. In a total of 139 episodes of infective endocarditis in IVDU, 72 (51.8%) cases were eligible for the two-week treatment. Of this group, 67 were cured, 4 needed prolongation of treatment to cure the infection and 1 died in hospital of respiratory distress syndrome on day 10 of treatment. In patients not eligible for the two-week treatment, the mortality was higher (24.2% versus 0.7%; p = 0.00015). Drug toxicity in the treated group was low. It can be concluded that administration of cloxacillin and amikacin parenterally for 14 consecutive days was successful in the therapy of right-sided endocarditis in IVDU.

[Comparison of the new Granada medium and the ICON-strep B test in the detection of group B streptococci in pregnant patients]. / Comparación del nuevo medio Granada y el test ICON-strep B en la detección de estreptococos del grupo B en gestantes.

The detection of group B streptococci by the ICON Strep-B test an enzyme immunoassay, and culture in new Granada Medium was compared in tubes and plates in a total of 200 vaginal specimens from pregnant women. The group B streptococci were cultured in new Granada medium from 33 of these specimens (incidence of 16.5%). Compared with culture in new Granada medium, the sensitivity and specificity of the ICON-Strep B test were 66.6 and 100%, respectively. Because of their poor sensitivity, we do not recommend the use of these rapid test as the only basis for GBS detection.