Objectiveswe assessed the incidence, risk factors and outcome of BSI over a 14-year period (2000–2013) in a Swedish county.Methodsretrospective cohort study on culture confirmed BSI among patients in the county of Östergötland, Sweden, with approximately 440,000 inhabitants. A BSI was defined as either community-onset BSI (CO-BSI) or hospital-acquired BSI (HA-BSI).Resultsof a total of 11,480 BSIs, 67% were CO-BSI and 33% HA-BSI. The incidence of BSI increased by 64% from 945 to 1,546 per 100,000 hospital admissions per year during the study period. The most prominent increase, 83% was observed within the CO-BSI cohort whilst HA-BSI increased by 32%. Prescriptions of antibiotics in outpatient care decreased with 24% from 422 to 322 prescriptions dispensed/1,000 inhabitants/year, whereas antibiotics prescribed in hospital increased by 67% (from 424 to 709 DDD per 1,000 days of care). The overall 30-day mortality for HA-BSIs was 17.2%, compared to 10.6% for CO-BSIs, with an average yearly increase per 100,000 hospital admissions of 2 and 5% respectively. The proportion of patients with one or more comorbidities, increased from 20.8 to 55.3%. In multivariate analyses, risk factors for mortality within 30 days were: HA-BSI (2.22); two or more comorbidities (1.89); single comorbidity (1.56); CO-BSI (1.21); male (1.05); and high age (1.04).Conclusionthis survey revealed an alarming increase in the incidence of BSI over the 14-year study period. Interventions to decrease BSI in general should be considered together with robust antibiotic stewardship programmes to avoid both over- and underuse of antibiotics.

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Colistin-susceptible isolates of Acinetobacter baumannii often contain subpopulations that are resistant to colistin. Monotherapy with colistin can lead to selective growth of these subpopulations and emergence of colistin-resistant strains. Our objectives were to explore the susceptibility pattern of colistin-resistant subpopulations and investigate if combining colistin with a second antibiotic could prevent their selective growth. Four colistin-susceptible clinical isolates of A. baumannii and one reference isolate were used. The mutant prevention concentration (MPC) of colistin, i.e. the concentration required to block growth of all single-step-mutant subpopulations, was determined by plating an inoculum of 109 CFU on Mueller Hinton agar (MHA)-plates containing 2-fold dilutions of colistin (0.125–128 mg/L). Susceptibility testing of colistin-resistant subpopulations, obtained in the MPC assay, was performed with Etest. The MPC of colistin, in combination with rifampicin, was determined by plating an inoculum of 109 CFU on MHA-plates containing colistin (0.125–128 mg/L) and fixed concentrations of rifampicin (1.1 mg/L or 4.4 mg/L). The colistin-resistant subpopulations demonstrated increased susceptibility to a number of agents compared to their main populations. These subpopulations were even susceptible to agents that normally are inactive against gram-negative bacteria and all had rifampicin MICs of < 0.002 mg/L. The combination of colistin and rifampicin completely inhibited the growth of all colistin-resistant subpopulations and significantly lowered the MPC of colistin for A. baumannii. Combining colistin with rifampicin could be a way to prevent selective growth of colistin-resistant subpopulations of A. baumannii and possibly the emergence of colistin-resistant strains.

Staphylococcus epidermidis often causes foreign-body infections such as those associated with hip prostheses, but the underlying pathogenic mechanisms are not fully understood. We performed spectrophotometry to study the ability of S. epidermidis to bind to immobilised fibrinogen, fibronectin, vitronectin, and collagen. The strains were isolated from infected hip prostheses or from normal flora and the well-known protein-binding strain Staphylococcus aureus Cowan was used as positive control. We also analysed the interaction between neutrophils and a fibrinogen-bound prosthesis-derived strain of S. epidermidisby measuring chemiluminescence to determine the neutrophil oxidative response and binding of annexin V to indicate neutrophil apoptosis. We found that binding of S. epidermidis to extracellular matrix proteins varied under different growth conditions, and that prosthesis isolates adhered better to vitronectin than did strains from normal flora. The oxidative response caused by fibrinogen-bound S. epidermidis was not above the background level, which was in marked contrast to the distinct response induced by fibrinogen-associated S. aureus Cowan. Furthermore, fibrinogen-adhering S. epidermidis retarded neutrophil apoptosis. We conclude that surface-bound S. epidermidis induces only a weak inflammatory response, which in combination with the ability of the adherent bacteria to retard neutrophil apoptosis may contribute to low-grade inflammation and loosening of prostheses.

The nosocomial opportunistic Gram-negative bacterial pathogen Acinetobacter baumannii is resistant to multiple antimicrobial agents and an emerging global health problem. The polymyxin antibiotic colistin, targeting the negatively charged lipid A component of the lipopolysaccharide on the bacterial cell surface, is often considered as the last-resort treatment, but resistance to colistin is unfortunately increasing worldwide. Notably, colistin-susceptible A. baumannii can also develop a colistin dependence after exposure to this drug in vitro. Colistin dependence might represent a stepping stone to resistance also in vivo. However, the mechanisms are far from clear. To address this issue, we combined proteogenomics, high-resolution microscopy, and lipid profiling to characterize and compare A. baumannii colistin-susceptible clinical isolate (Ab-S) of to its colistin-dependent subpopulation (Ab-D) obtained after subsequent passages in moderate colistin concentrations. Incidentally, in the colistin-dependent subpopulation the lpxA gene was disrupted by insertion of ISAjo2, the lipid A biosynthesis terminated, and Ab-D cells displayed a lipooligosaccharide (LOS)-deficient phenotype. Moreover, both mlaD and pldA genes were perturbed by insertions of ISAjo2 and ISAba13, and LOS-deficient bacteria displayed a capsule with decreased thickness as well as other surface imperfections. The major changes in relative protein abundance levels were detected in type 6 secretion system (T6SS) components, the resistance-nodulation-division (RND)-type efflux pumps, and in proteins involved in maintenance of outer membrane asymmetry. These findings suggest that colistin dependence in A. baumannii involves an ensemble of mechanisms seen in resistance development and accompanied by complex cellular events related to insertional sequences (ISs)-triggered LOS-deficiency. To our knowledge, this is the first study demonstrating the involvement of ISAjo2 and ISAba13 IS elements in the modulation of the lipid A biosynthesis and associated development of dependence on colistin.