Characteristics and Outcomes of Staphylococcus aureus Bloodstream Infection Originating From the Urinary Tract: A Multicenter Cohort Study.

BACKGROUND: Staphylococcus aureus bloodstream infection (SABSI) arising from a urinary tract source (UTS) is poorly understood. METHODS: We conducted a retrospective analysis in 3 major teaching hospitals in Spain of prospectively collected data of hospitalized patients with SABSI. SABSI-UTS was diagnosed in patients with urinary tract symptoms and/or signs, no evidence of an extra-urinary source of infection, and a urinary S. aureus count of ≥105 cfu/mL. Susceptibility of S. aureus strains and patient mortality were compared between SABSI from UTS (SABSI-UTS) and other sources (SABSI-other). RESULTS: Of 4181 episodes of SABSI, we identified 132 (3.16%) cases of SABSI-UTS that occurred predominantly in patients who were male, had high Charlson comorbidity scores, were dependent for daily life activities, and who had undergone urinary catheterization and/or urinary manipulation before the infection. SABSI-UTS was more often caused by MRSA strains compared with SABSI-other (40.9% vs 17.5%; P < .001). Patients with SABSI-UTS caused by MRSA more often received inadequate empirical treatment compared with those caused by susceptible strains (59.7% vs 23.1%; P < .001). The 30-day case fatality rate was lower in patients with SABSI-UTS than in those with SABSI-other (14.4% vs 23.8%; P = .02). Factors independently associated with mortality were dependence for daily activities (aOR, 3.877; 95% CI, 1.08-13.8; P = .037) and persistent bacteremia (aOR, 7.88; 95% CI, 1.57-39.46; P = .012). CONCLUSIONS: SABSI-UTS occurs predominantly in patients with severe underlying conditions and in those who have undergone urinary tract manipulation. Moreover, it is frequently due to MRSA strains and causes significant mortality.

Delayed Cerebral Vasculopathy in Pneumococcal Meningitis: Epidemiology and Clinical Outcome. A Cohort Study.

BACKGROUND: To describe the prevalence, clinical characteristics, impact of systemic steroids exposure and outcomes of delayed cerebral vasculopathy (DCV) in a cohort of adult patients with pneumococcal meningitis (PM). METHODS: Observational retrospective multicenter study including all episodes of PM from January 2002 to December 2015. DCV was defined as proven/probable/possible based upon clinical criteria and pathological-radiological findings. DCV-patients and non-DCV-patients were compared by univariate analysis. RESULTS: 162 PM episodes were included. Seventeen (10.5%) DCV-patients were identified (15 possible, 2 probable). At admission, DCV-patients had a longer duration of symptoms (>2 days in 58% vs. 25.5% (p 0.04)), more coma (52.9% vs. 21.4% (p 0.03)), lower median CSF WBC-count (243 cells/uL vs. 2673 cells/uL (p 0.001)) and a higher proportion of positive CSF Gram stain (94.1% vs. 71% (p 0.07)). Median length of stay was 49 vs. 15 days (p 0.001), ICU admission was 85.7% vs. 49.5% (p 0.01) and unfavorable outcome was found in 70.6% vs. 23.8% (p 0.001). DCV appeared 1-8 days after having completed adjunctive dexamethasone treatment (median 2,5, IQR=1.5-5). CONCLUSIONS: One tenth of the PM developed DCV. DCV-patients had a longer duration of illness, were more severely ill, had a higher bacterial load at admission and had a more complicated course. Less than one third of cases recovered without disabilities. The role of corticosteroids in DCV remains to be established.

Management of Ventriculoperitoneal Shunt Infections in Adults: Analysis of Risk Factors Associated With Treatment Failure.

Background: Little is known regarding the optimal treatment of ventriculoperitoneal (VP) shunt infections in adults. Our aim was to assess the efficacy of treatment strategies and to identify factors that predict failure. Methods: Retrospective, observational study of patients aged ≥12 years with VP shunt infections (1980 -2014). Therapeutic approaches were classified under 4 headings: only antibiotics (OA), one-stage shunt replacement (OSSR), two-stage shunt replacement (TSSR), and shunt removal without replacement (SR). The primary endpoint was failure of the treatment strategy, defined as the absence of definite cerebrospinal fluid (CSF) sterilization or related mortality. The parameters that predicted failure were analyzed using logistic regression. Results: Of 108 episodes (51% male, median age 50 years), 86 were analyzed. Intravenous antibiotics were administered for a median of 19 days. Eighty episodes were treated using strategies that combined antibiotic and surgical treatment (37 TSSR, 24 SR, 19 OSSR) and 6 with OA. Failure occurred in 30% of episodes, mostly due to lack of CSF sterilization in OSSR and OA groups. Twelve percent died of related causes and 10% presented superinfection of the CSF temporary drainage/externalized peritoneal catheter. TSSR was the most effective strategy when VP shunt replacement was attempted. The only independent risk factor that predicted failure was retention of the VP shunt, regardless of the strategy. Conclusions: This is the largest series of VP shunt infections in adults reported to date. VP shunt removal, particularly TSSR when the patient is shunt dependent, remains the optimal choice of treatment and does not increase morbidity.

The anti-biofilm effect of macrolides in a rat model of S. aureus foreign-body infection: Might it be of clinical relevance?

Using a tissue cage infection rat model, we test the anti-biofilm effect of clarithromycin on the efficacy of daptomycin and a daptomycin + rifampicin combination against methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). In vitro: kill curves, daptomycin exposure studies and clarithromycin activity against biofilm were studied. In vivo: the efficacies of clarithromycin, daptomycin or daptomycin + clarithromycin, daptomycin + rifampicin and daptomycin + rifampicin + clarithromycin combinations were evaluated. In vitro: the addition of clarithromycin to daptomycin improved its activity only against one MRSA strain. Changes in daptomycin MIC values appeared more quickly in MSSA than in MRSA strain, and this was not modified by clarithromycin. Clarithromycin prevented biofilm formation but did not eradicate it. In vivo: the daptomycin + rifampicin combination was the most effective treatment and was not improved by the addition of clarithromycin. Daptomycin and daptomycin + clarithromycin had similar effectiveness; the combination protected against the appearance of daptomycin resistance only in one MRSA strain. Using a staphylococcal foreign-body infection model, we observed a slight effect with the addition of clarithromycin to daptomycin, which resulted in protection against the appearance of daptomycin-resistant strains. However, efficacy was not improved. Overall, our findings do not support a relevant clinical role for macrolides in treating device-related staphylococcal infections based on their anti-biofilm effect.

Identification of Haemophilus haemolyticus in clinical samples and characterization of their mechanisms of antimicrobial resistance.

OBJECTIVES: The objectives of this study were to establish the frequency of Haemophilus haemolyticus in clinical samples, to determine the antimicrobial resistance rate and to identify the mechanisms of resistance to ß-lactams and quinolones. METHODS: An updated database was used to differentiate between MALDI-TOF MS results for Haemophilus influenzae and H. haemolyticus. Antimicrobial susceptibility was studied by microdilution, following EUCAST criteria. The ß-lactamase types were identified by PCR analysis of isolates that tested positive for nitrocefin hydrolysis. Mutations in the ftsI gene were identified in isolates with ampicillin MICs ≥0.25 mg/L. Mutations in the quinolone resistance-determining region (QRDR) were identified in isolates with ciprofloxacin MICs ≥0.5 mg/L. RESULTS: Overall, we identified 69 H. haemolyticus isolates from 1706 clinical isolates of Haemophilus spp. from respiratory, genital, invasive, and other infection sources. The frequency of H. haemolyticus was low in respiratory samples compared with that of H. influenzae, but in genital-related samples, the frequency was similar to that of H. influenzae. We found low antimicrobial resistance rates among H. haemolyticus isolates, with 8.7% for ampicillin, 8.7% for co-trimoxazole, 7.2% for tetracycline and 4.3% for ciprofloxacin. Mutations in the ftsI gene classified the isolates into four groups, including the newly described Group Hhae IV, which presents mutations in the ftsI gene not identified in H. influenzae and H. haemolyticus type strains. Three ciprofloxacin-resistant H. haemolyticus isolates with mutations affecting GyrA and ParC were identified. CONCLUSIONS: The frequency of H. haemolyticus was low, especially in respiratory samples, where H. influenzae is the main pathogen of this genus. Although antimicrobial resistance rates were low, three ciprofloxacin-resistant H. haemolyticus clinical isolates have been identified for the first time.

Daptomycin combinations as alternative therapies in experimental foreign-body infection caused by meticillin-susceptible Staphylococcus aureus.

Whilst levofloxacin (LVX) in combination with rifampicin (RIF) is considered the optimal treatment for prosthetic joint infection (PJI) caused by meticillin-susceptible Staphylococcus aureus (MSSA), no therapeutic alternatives have been accurately evaluated. Based on the high effectiveness of the combination of daptomycin (DAP) plus RIF against meticillin-resistant S. aureus (MRSA) in this setting, in this study the efficacy of DAP+RIF and DAP+LVX combinations was tested as alternative therapies for foreign-body infections (FBIs) caused by MSSA. A tissue-cage infection model was performed using an MSSA strain. Male Wistar rats were treated for 7 days with LVX, DAP, RIF or the combinations LVX+RIF, DAP+RIF and DAP+LVX. Antibiotic efficacy was evaluated by bacterial counts from tissue cage fluid (TCF) and the cure rate was determined from adhered bacteria. Resistance was screened. Monotherapies were less effective than combinations (P<0.05), and resistance to DAP and RIF emerged. DAP+RIF (decrease in bacterial counts in TCF, -4.9logCFU/mL; cure rate, 92%) was the most effective therapy (P<0.05). There were no differences between LVX+RIF (-3.4logCFU/mL; 11%) and DAP+LVX (-3.3logCFU/mL; 47%). No resistant strains appeared with combined therapies. In conclusion, the combinations DAP+RIF and DAP+LVX showed good efficacy and prevented resistance. DAP+RIF provided higher efficacy than LVX+RIF. These DAP combinations were efficacious alternatives therapies for MSSA FBI. Further studies should confirm whether DAP+RIF may be useful as a first-line therapy in the setting of PJI caused by MSSA.

Comparative efficacies of cloxacillin-daptomycin and the standard cloxacillin-rifampin therapies against an experimental foreign-body infection by methicillin-susceptible Staphylococcus aureus.

We compared the efficacies of daptomycin (doses equivalent to 8 to 10 mg/kg of body weight/day in humans) and cloxacillin alone with those of cloxacillin-rifampin and cloxacillin-daptomycin combinations, using a tissue cage methicillin-susceptible Staphylococcus aureus (MSSA) infection model. Monotherapies were less effective than combinations (P<0.05), and daptomycin resistance emerged. Cloxacillin-daptomycin proved as effective as cloxacillin-rifampin and prevented the appearance of resistance; this combination may be an alternative anti-MSSA therapy, which may offer greater benefits in the early treatment of prosthetic joint infections (PJI).

Dynamics of the pneumococcal population causing acute exacerbations in COPD patients in a Barcelona hospital (2009-12): comparison with 2001-04 and 2005-08 periods.

BACKGROUND: Pneumococci are an important cause of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). In the last decade, the pneumococcal population has changed, mainly due to the introduction of the 7-valent conjugate vaccine (PCV7). METHODS: We analysed the antimicrobial susceptibility (microdilution), serotype (PCR) and genotype (PFGE/multilocus sequence typing) of pneumococci causing acute exacerbations during the period 2009-12. Results were compared with two previously published historic periods (2001-04 and 2005-08). RESULTS: A total of 206 pneumococci were collected from 162 COPD patients with acute exacerbations. Compared with previous periods, no significant changes in the rate of multidrug resistance were observed (36.2% in the 2001-04 period to 33.5% in the 2009-12 period, P = 0.644). The most frequent serotypes in the 2009-12 period were 15A (9.6%), 3 (8.1%), 19F (6.6%), 11A (6.1%) and 6C (5.6%), which accounted for 36.0%. A drastic decrease in PCV7 serotypes was observed throughout the study period (from 39.7% in 2001-04 to 10.9% in 2009-12, P < 0.001); non-PCV13 serotypes increased from 44.9% to 71.2%, especially 15A (from 2.2% to 9.6%) and 6C (from 0.0% to 5.6%) (P < 0.05). The most frequent genotypes (clonal complexes, CCs) in the 2009-12 period were CC63(15A,19F,15F) (9.1%), CC180(3) (4.5%), CC62(11A) (4.0%), CC97(10A) (4.0%), CC386(6C) (3.5%), CC260(3) (3.5%) and CC30(16F) (3.5%). Serotypes 19F, 19A, 6A and 6C were genetically diverse. CONCLUSIONS: PCV7 serotypes have decreased dramatically. In parallel, two non-PCV7 serotypes (15A and 6C) and their related genotypes (CC63 and CC386) showed a significant increase. Although resistance rates to ß-lactams decreased over time, multidrug resistance remained stable.

Infected hip hemiarthroplasties and total hip arthroplasties: Differential findings and prognosis.

OBJECTIVES: Infected hip hemiarthroplasties (HHA) are classically analyzed along with infected total hip arthroplasties (THA), but patients with either one or other device are different. We describe the clinical presentation, etiology and prognosis of infected HHA compared with infected THA. METHODS: Comparative study of patients with infected HHA and THA from a prospective database of prosthetic joint infection (PJI) cases in our hospital (2003-2011), focusing on patients managed with debridement, antibiotics and implant retention (DAIR). RESULTS: 210 episodes of hip-PJI (age 74 years, 63% women): 62 (39%) HHA and 148 (61%) THA. HHA-patients were older and had more comorbidities. Late-chronic and hematogenous infections were more frequent in THA. 123 (59%) patients were managed with DAIR: 72 THA and 51 HHA. Staphylococcus aureus was more frequent in THA (44% vs 26%, p = 0.032), while Gram-negative bacilli were more prevalent in HHA (73% vs 51%, p = 0.018), with a higher prevalence of fluoroquinolone-resistance in cemented-HHA. Overall failure was 37%, with no significant differences among groups. A higher mortality was observed in HHA cases (21% vs 4%, p = 0.005), particularly in cemented-HHA. CONCLUSION: Infected THA and HHA have different characteristics, etiology and prognosis. Overall failure was similar, probably balanced by different predictors among groups, but mortality was higher among cemented-HHA.

Rainfall is a risk factor for sporadic cases of Legionella pneumophila pneumonia.

It is not known whether rainfall increases the risk of sporadic cases of Legionella pneumonia. We sought to test this hypothesis in a prospective observational cohort study of non-immunosuppressed adults hospitalized for community-acquired pneumonia (1995-2011). Cases with Legionella pneumonia were compared with those with non-Legionella pneumonia. Using daily rainfall data obtained from the regional meteorological service we examined patterns of rainfall over the days prior to admission in each study group. Of 4168 patients, 231 (5.5%) had Legionella pneumonia. The diagnosis was based on one or more of the following: sputum (41 cases), antigenuria (206) and serology (98). Daily rainfall average was 0.556 liters/m(2) in the Legionella pneumonia group vs. 0.328 liters/m(2) for non-Legionella pneumonia cases (p = 0.04). A ROC curve was plotted to compare the incidence of Legionella pneumonia and the weighted median rainfall. The cut-off point was 0.42 (AUC 0.54). Patients who were admitted to hospital with a prior weighted median rainfall higher than 0.42 were more likely to have Legionella pneumonia (OR 1.35; 95% CI 1.02-1.78; p = .03). Spearman Rho correlations revealed a relationship between Legionella pneumonia and rainfall average during each two-week reporting period (0.14; p = 0.003). No relationship was found between rainfall average and non-Legionella pneumonia cases (-0.06; p = 0.24). As a conclusion, rainfall is a significant risk factor for sporadic Legionella pneumonia. Physicians should carefully consider Legionella pneumonia when selecting diagnostic tests and antimicrobial therapy for patients presenting with CAP after periods of rainfall.