High Perineal and Overall Frequency of Staphylococcus aureus in People Who Inject Drugs, Compared to Non-Injectors.

To investigate the prevalence, distribution, and colonization burden of Staphylococcus aureus (S. aureus) and MRSA in different body sites among people who inject drugs (PWID) and compare it to a control group consisting of non-injectors. In this cross-sectional survey, 49 active PWID from the needle exchange program (NEP) in Malmö, Sweden, and 60 non-injecting controls from an emergency psychiatric inpatient ward at Malmö Addiction Centre were tested for S. aureus (including MRSA) by culture, PCR, and MALDI-TOF. Samples were taken from anterior nares, throat, perineum, and skin lesions if present. Sixty-seven percent of the PWID were colonized with S. aureus, compared to 50% of the controls (P = 0.08). Perineal carriage was significantly more frequent among PWID than in the control group [37 vs 17%, OR 2.96 (95% CI 1.13-7.75), P = 0.03], also after adjusting for sex and age in multivariate analysis [OR 4.01 (95% CI 1.34-12.03)]. Only one individual in the whole cohort (NEP participant) tested positive for MRSA. PWID may be more frequently colonized with S. aureus in the perineum than non-injection drug users, and there was a trend indicating more frequent overall S. aureus colonization in PWID, as well as higher perineal colonization burden. No indication of a high MRSA prevalence among PWID in Sweden was noted. However, further MRSA prevalence studies among PWID are needed. Knowledge about S. aureus colonization is important for the prevention of S. aureus infections with high morbidity in PWID.

LTX-109 is a novel agent for nasal decolonization of methicillin-resistant and -sensitive Staphylococcus aureus.

Nasal decolonization has a proven effect on the prevention of severe Staphylococcus aureus infections and the control of methicillin-resistant S. aureus (MRSA). However, rising rates of resistance to antibiotics highlight the need for new substances for nasal decolonization. LTX-109 is a broad-spectrum, fast-acting bactericidal antimicrobial drug for topical treatment, which causes membrane disruption and cell lysis. This mechanism of action is not associated with cross-resistance and has a low propensity for development of resistance. In the present study, persistent nasal MRSA and methicillin-sensitive S. aureus (MSSA) carriers were treated for 3 days with vehicle or with 1%, 2%, or 5% LTX-109. A significant effect on nasal decolonization was observed already after 2 days of LTX-109 treatment in subjects treated with 2% or 5% LTX-109 compared to vehicle (P ≤ 0.0012 by Dunnett's test). No safety issues were noted during the 9-week follow-up period. Minimal reversible epithelial lesions were observed in the nasal cavity. The systemic exposure was very low, with a maximum concentration of drug in plasma (Cmax) at 1 to 2 h postdosing (3.72 to 11.7 ng/ml). One week after treatment initiation, LTX-109 was not detectable in any subject. Intranasal treatment of S. aureus with LTX-109 is safe and reduces the bacterial load already after a single day of treatment. Hence, LTX-109 has potential as a new and effective antimicrobial agent with a low propensity of resistance development that can prevent infections by MSSA/MRSA during hospitalization. (This study has been registered at ClinicalTrials.gov under registration no. NCT01158235.).

Staphylococcus aureus carriage and prevalence of skin and soft tissue infections among people who inject drugs: a longitudinal study.

People who inject drugs are frequently colonized with Staphylococcus aureus and have an increased risk for skin and soft tissue infections. This longitudinal study aims to describe S. aureus carriage in this group and the risk for infections during a 1-year follow-up. We included 61 participants from the Malmö Needle Exchange Program. Mapping of S. aureus carriage was conducted by screening cultures every third month and S. aureus growth was semi-quantified. Data regarding infections and living conditions were collected from structured interviews. Statistics included univariate analysis with the Fischer's exact test, univariate logistic regression and multivariate logistic regression. S. aureus carriage was detected in 46-63% of participants, and 75% reported one or more infections during the study period. Self-reported infections were associated with carriage in perineum (OR 5.08 [95% CI 1.45-17.73]), in skin lesions (OR 1.48 [95% CI 1.21-1.81]), and unstable housing situation (OR 12.83 [95% CI 1.56-105.81]). Thus, people who inject drugs are frequent carriers of S. aureus and report a surprisingly high prevalence of skin and soft tissue infections. Homeless people and those with skin carriage seem to be at highest risk. Effective clinical interventions are needed, aiming at preventing infections in this vulnerable group.

Risk Factors for Infection After Transrectal Prostate Biopsy: A Population-based Register Study.

Background and objective: Infection after transrectal prostate biopsy (TPBx) is a well-known risk. A comprehensive investigation of risk factors may identify measures for safe TPBx as an alternative to a change in biopsy route. The aim of this study was to identify risk factors for infection after TPBx. Methods: We included all outpatient TPBx cases in Region Kronoberg, Sweden, from January 2010 to December 2019. The primary outcome was post-TPBx infection, defined as prescription of antibiotics indicated for urinary tract infection (UTI) or inpatient care for infection within 30 d. We analysed the following factors in relation to post-TPBx infection: age, diabetes mellitus, prostate cancer diagnosed at index biopsy, previous prostate biopsy, two or more biopsies in the past 24 mo, a positive urine culture, two or more negative urine cultures (UCs) in the past 24 mo, antibiotic treatment grouped as four types, and medication for benign prostatic hyperplasia (BPH). Logistic regression was used to calculate odds ratios (ORs). Key findings and limitations: Of 5788 TPBx procedures in 4040 patients, 405 (7.0%) led to an infection and 170 (2.9%) to inpatient care for infection. Risk factors for post-TPBx infection (ORs 1.5-2.5) were diabetes mellitus, antibiotic treatment for a UTI, fluoroquinolone treatment, and a positive urine culture. Weaker risk factors (ORs 1.3-1.5) were non-UTI antibiotic treatment, BPH medication, and negative UCs before TPBx. Conclusions and clinical implications: Our results confirm that diabetes mellitus and previous UTI are risk factors for infection after TPBx. Lower urinary tract symptoms and treatment with any kind of antibiotic were associated with infection, which has not been previously reported. Patient summary: In a large population-based study from Sweden, we investigated which clinical factors increase the risk of an infection after transrectal prostate biopsy. Our results confirm that diabetes and a previous urinary tract infection are risk factors. We also found two new factors associated with the risk of infection after biopsy: lower urinary tract symptoms and any antibiotic treatment.

Clinical Value of a Routine Urine Culture Prior to Transrectal Prostate Biopsy.

Background: Infectious complications after a transrectal prostate biopsy may be severe. In Sweden, a routine culture prior to all prostate biopsies was introduced to enable targeted antimicrobial prophylaxis and reduce postbiopsy infections. Objective: To investigate whether a clinical routine with a urine culture prior to a prostate biopsy and targeted prophylactic antibiotic therapy reduces postbiopsy infections. Design setting and participants: In 2015, a site-specific antimicrobial stewardship programme with a urine culture prior to a prostate biopsy was initiated in Region Kronoberg. To evaluate this routine, we designed a population-based register study including all men who had an outpatient prostate biopsy in 2015-2019 and a control period including all men who had a biopsy in 2010-2014, when a urinary culture was obtained only on clinical suspicion. Outcome measurements and statistical analysis: The primary outcome was infectious complications within 10 d and the secondary outcome was a change in antibiotic prophylactic treatment. An infectious complication was defined as prescription of antibiotics for urinary tract infections or admission to hospital for urinary tract infections or sepsis after a biopsy. Results and limitations: The urine culture period included 2971 prostate biopsy procedures, of which 2684 (90%) were preceded by a urine culture. The control period included 2818 procedures, of which 135 (4.8%) were preceded by a urine culture. Infectious complications were slightly more common during the urine culture period (5.0%) than during the control period (4.3%, p = 0.17), as was inpatient care for infections (3.5% vs 2.2%, p = 0.002). The routine identified 5.4% men with asymptomatic bacteriuria. Despite targeted antibiotic treatment (1.5% received a nonfluoroquinolone treatment), the rate of infectious complications (6.3%) was similar to that in the control period. Conclusions: Prebiopsy urine culture did not lead to fewer postbiopsy infections. Other measures are needed to reduce infectious complications after a prostate biopsy. Patient summary: In this report, we evaluated a routine with urine culture prior to a transrectal prostate biopsy and found that it did not lead to fewer infectious complications.

Decline of the new Swedish variant of Chlamydia trachomatis after introduction of appropriate testing.

OBJECTIVE: The longitudinal epidemiological development of the new variant of Chlamydia trachomatis was studied after appropriate testing procedures had been introduced when the strain was detected in 2006. METHODS: The number of cases of the new variant of C trachomatis was followed from 2007 through 2011 from the laboratory records. Testing for C trachomatis is centralised to one laboratory with around 80-85 000 persons being tested annually in a population of 1.1 million. RESULTS: During the 5-year period, 410 973 patients were tested of which 25 723 cases were positive. The proportion of the new variant of all positive cases declined from 30% in 2007 to 6% in 2011. While the number of the new variant of C trachomatis declined, the ordinary wild-type strains remained largely unchanged. CONCLUSIONS: A selective decline of the new variant of C trachomatis has occurred after appropriate laboratory testing was introduced. A new balance point between 5% and 10% for the new variant seems to be gradually approached.

Protein D of Haemophilus influenzae: a protective nontypeable H. influenzae antigen and a carrier for pneumococcal conjugate vaccines.

Protein D (PD) is a highly conserved 42 kDa surface lipoprotein found in all Haemophilus influenzae, including nontypeable (NT) H. influenzae. PD is involved in the pathogenesis of respiratory tract infections, in the context of which it has been shown to impair ciliary function in a human nasopharyngeal tissue culture model and to augment the capacity to cause otitis media in rats. A likely mechanism indicating that PD is a virulence factor is its glycerophosphodiesterase activity, which leads to the release of phosphorylcholine from host epithelial cells. PD has been demonstrated to be a promising vaccine candidate against experimental NT H. influenzae infection. Rats vaccinated with PD cleared NT H. influenzae better after middle ear and pulmonary bacterial challenge, and chinchillas vaccinated with PD showed significant protection against NT H. influenzae-dependent acute otitis media. In a clinical trial involving children, PD was used as an antigenically active carrier protein in an 11-valent pneumococcal conjugate investigational vaccine; significant protection was achieved against acute otitis media not only caused by pneumococci but also caused by NT H. influenzae. This may have great clinical implications, because PD is the first NT H. influenzae antigen that has induced protective responses in humans.

Identification of a novel Haemophilus influenzae protein important for adhesion to epithelial cells.

Non-typable Haemophilus influenzae (NTHi) is an important human-specific respiratory pathogen colonizing the mucosa of the upper respiratory tract. The bacterium is a common cause of acute otitis media in children and exacerbations in patients with chronic obstructive pulmonary disease (COPD). An immunoglobulin (Ig) D-lambda myeloma protein was found to detect a 16 kDa surface protein that we designated protein E (PE). The pe gene was cloned using an NTHi genomic DNA library, and a truncated PE-derived protein lacking the endogenous signal peptide (PE22-160) was synthesized and produced in large amounts in Escherichia coli. Interestingly, PE was expressed at the bacterial surface of NTHi as revealed by flow cytometry using the IgD-lambda myeloma protein or PE-specific polyclonal antibodies. A PE-deficient NTHi mutant was produced and lost 50% of its adhesive capacity as compared to the wild-type counterpart when analysed for adhesion to type II lung alveolar epithelial cells. In parallel, E. coli expressing full-length PE1-160 adhered significantly more efficiently to epithelial cells as compared to wild-type E. coli. Recombinant IgD that recognized the chemical dansyl-chloride did not interact with PE indicating that the IgD-lambda myeloma protein most likely was an antibody directed against the H. influenzae surface epitope. In conclusion, we have discovered a novel NTHi outer membrane protein with adhesive properties using an IgD-myeloma protein.

The majority of MRSA colonized children not given eradication treatment are still colonized one year later. Systemic antibiotics improve the eradication rate.

BACKGROUND: Colonization with methicillin-resistant Staphylococcus aureus (MRSA) can cause endogenously derived infections and be a source of transmission to other people. Neither colonization time of asymptomatic MRSA colonization nor the effect of treatment aiming at MRSA eradication in children has been thoroughly investigated. METHODS: Two hundred ninety-three children <18 years in the mandatory follow-up program for MRSA-carriers in Malmö, Sweden were evaluated. Samples from the throat, nares, perineum and skin lesions from each child were screened for MRSA with a PCR-based broth enrichment method. PVL presence and spa-type were evaluated in a majority of cases. The sampling was repeated approximately every 6 month after initial detection. When three consecutive sets of negative samples during at least a 6-month period were obtained, the MRSA was considered permanently eradicated. MRSA eradication treatment given, on clinical grounds during follow-up, was noted. RESULTS: One year after detection 62% of the untreated children were still MRSA positive and after 2 years 28%. MRSA throat colonization and having MRSA positive household contacts significantly prolonged the observed colonization time. Topical MRSA eradication treatment was successful in 36% of cases and in 65% if systemic antibiotics were added. Presence of PVL correlated with shorter observed colonization time in the older age group and with increased eradication success among throat carriers. CONCLUSION: MRSA throat colonization and having MRSA positive household contacts prolongs the time of MRSA colonization in children. Systemic antibiotics enhance the effect of MRSA eradication treatment.

Actinobacillus pleuropneumoniae: pathobiology and pathogenesis of infection.

Actinobacillus pleuropneumoniae causes porcine pleuropneumonia, a highly contagious disease for which there is no effective vaccine. This review considers how adhesins, iron-acquisition factors, capsule and lipopolysaccharide, RTX cytotoxins and other potential future vaccine components contribute to colonisation, to avoidance of host clearance mechanisms and to damage of host tissues.

Differences in genetic and transcriptional organization of the glpTQ operons between Haemophilus influenzae type b and nontypeable strains.

The glpTQ operon of Haemophilus influenzae type b (Hib) and nontypeable H. influenzae (NTHi) strains is highly conserved, except for a 1.4-kb glpTQ intergenic region that was found in most Hib strains. The presence of this intergenic region results in divergent glpTQ transcriptional profiles for Hib and NTHi where Hib strains appear to have evolved an alternative promoter for glpQ expression. Based on the intergenic region's low G+C content, we speculate that this DNA fragment was acquired by lateral transfer.