Risk factors for candidaemia in hospitalized patients with liver cirrhosis: a multicentre case–control–control study

ObjectivesThe aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis.MethodsThis was a case–control–control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission.ResultsDuring the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09–4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19–4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00–7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26–6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62–9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11–10.18), p <0.001] Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19–0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97–2.75) p = 0.06).ConclusionsWe identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor.     

Risk factors for community-onset bloodstream infection with extended-spectrum β-lactamase-producing Enterobacteriaceae: national population-based case–control study

ObjectivesThe aim was to investigate risk factors for community-onset bloodstream infections with extended-spectrum β-lactamase-producing Enterobacteriaceae (EPE BSI).MethodsIt is mandatory to report EPE BSI to a national register at the Public Health Agency of Sweden. Using this register, we performed a population-based case–control study from 2007 to 2012 of 945 cases and 9390 controls. Exposure data on comorbidity, hospitalization, in- and outpatient antibiotic consumption and socio-economic status were collected from hospital and health registers.ResultsThe overall incidence of EPE BSI was 1.7 per 100 000 person-years. The 30-day mortality was 11.3%. Urological disorders inferred the highest EPE BSI risk, adjusted odds ratio (aOR) 4.32 (95% Confidence Interval (CI) 3.41–5.47), followed by immunological disorders, aOR 3.54 (CI 2.01–6.23), haematological malignancy, aOR 2.77 (CI 1.57–4.87), solid tumours, aOR 2.28 (1.76–2.94) and diabetes, aOR 2.03 (1.58–2.61). Consumption of fluoroquinolones or mostly non-EPE-active antibiotics with selective Gram-negative spectrum of activity within the previous 3 months was associated with EPE BSI, aORs 5.52 (CI 2.8–11.0) and 3.8, CI 1.9–7.7) respectively. There was a dose–response relationship in EPE BSI risk with increasing number of consecutive regimens. Antibiotic consumption >3 months before EPE BSI was not associated with increased risk. Higher age, malignancies and education ≤12 years (aORs >2) were associated with increased 30-day mortality.ConclusionsTargeted interventions should be directed towards improving care for patients with immunosuppression, urological disorders and subjects with lower socio-economic status. Antibiotic stewardship should focus on reduction of fluoroquinolones.     

Periodontal infections and community-acquired pneumonia: a case–control study

The aim of this study was to evaluate if the presence of periodontal infections (PI) is associated with community-acquired pneumonia (CAP) in a group of patients admitted to a hospital. A total of 140 patients were enrolled in this case–control study, with 70 patients having CAP (case group) and the other 70 patients diagnosed with other systemic diseases (control group). A periodontal examination was carried out to assess pocket probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), and presence of bacterial plaque (BP). CAL and BOP showed higher scores in the case group over the control group. They were, respectively, 3.16?±?2.43 mm and 0.33?±?0.24 % for the case group, and 1.99?±?2.23 mm and 0.25?±?0.24 % for the control group (p?<?0.05). High scores for BP were observed in both groups (case: 97.1 %; control: 98.6 %, p?=?1.0000). Chronic periodontitis (CP) was more frequent in patients with CAP (case: 61.4 %; control: 41.4 %). The presence of moderate or severe CP increased the risk for CAP [odds ratio (OR)?=?4.4, 95 % confidence interval (CI)?=?1.4–13.8], even when adjusted for age, ethnicity, gender, and smoking. Moderate and severe chronic periodontitis were associated with CAP in this study.     

Risk factors for Cutibacterium acnes spinal implant-associated infection: a case–case–control study

ObjectivesThe aim was to determine the characteristics of patients who developed Cutibacterium acnes spinal implant-associated infection (SIAI) and the associated risk factors.MethodsWe conducted two parallel case–control studies comparing 59 patients with SIAI caused by C. acnes (cases 1) and 93 patients with SIAI caused by other microorganisms (cases 2) diagnosed during 2010–2015 with 302 controls who underwent spinal instrumentation without subsequent infection.ResultsLate-onset infections (median time to diagnosis, 843 days versus 23 days; p < 0.001) were more common in cases 1 than in cases 2. However, 20/59 (34%) of cases 1 occurred within the first 3 months after the index surgery. In addition, cases 1 were less likely to have fever (27%, 16/59 versus 58%, 54/93; p 0.001) or wound inflammation (39%, 23/59 versus 72%, 67/93; p < 0.001). Moreover, 24/59 (40%) of cases 1 presented with polymicrobial infections, and staphylococcal pathogens accounted for 22/24 (92%) of the co-infections. By comparing and contrasting the two multivariate risk models (cases 1 versus controls and cases 2 versus controls), the following factors associated with C. acnes SIAI development were identified: age <54 years (adjusted odds ratio (aOR) 2.43, 95% confidence interval (CI) 1.09–5.58, p 0.03), a body mass index <22 kg/m² (aOR 2.47, 95% CI 1.17–5.29, p 0.02), and thoracic instrumentation (aOR 16.1, 95% CI 7.57–37.0, p < 0.001).ConclusionsFuture therapeutic and prophylactic studies on C. acnes SIAI should focus on young, thin patients who undergo spinal instrumentation procedures involving the thoracic spine.     

Splenectomy correlates with increased risk of pulmonary tuberculosis: a case–control study in Taiwan

This study investigated whether there was an association between splenectomy and pulmonary tuberculosis. This was a case–control study using the database of the Taiwan National Health Insurance Programme. We identified 18 960 patients (aged 20 years or older) with newly diagnosed pulmonary tuberculosis as the case group and 73 988 participants without pulmonary tuberculosis as the control group from 1998 to 2011. Both groups were matched for sex, age (per 5 years) and index year of pulmonary tuberculosis diagnosis. The risk of pulmonary tuberculosis associated with splenectomy and other co-morbidities was estimated. After controlling for confounders, multivariable logistic regression analysis showed that the odds of pulmonary tuberculosis were 1.91 in patients with splenectomy (95% CI 1.06–3.44), compared with the participants without splenectomy. Chronic obstructive pulmonary diseases (OR 3.07, 95% CI 2.94–3.21), pneumoconiosis (OR 2.20, 95% CI 1.90–2.56), chronic kidney diseases (OR 1.49, 95% CI 1.33–1.67), diabetes mellitus (OR 1.57, 95% CI 1.50–1.64) and chronic liver diseases (OR 1.31, 95% CI 1.25–1.37) were associated with an increased risk of pulmonary tuberculosis. The sub-analysis demonstrated that the odds of pulmonary tuberculosis were 4.81 (95% CI 2.31–10.0) for patients co-morbid with splenectomy and any of the above diseases. Splenectomy is associated with a 1.9-fold increased risk of pulmonary tuberculosis in Taiwan. There is a synergistic effect between splenectomy and other co-morbidities on the risk of pulmonary tuberculosis.     

Risk factors for levofloxacin-nonsusceptible Streptococcus pneumoniae in community-acquired pneumococcal pneumonia: a nested case–control study

This study was performed to evaluate the clinical features of community-onset levofloxacin-nonsusceptible pneumococcal pneumonia and to identify risk factors for levofloxacin resistance. Using the database of a surveillance study of community-acquired pneumococcal infections in Asian countries, we conducted a nested case–control study to identify risk factors for levofloxacin-nonsusceptible S. pneumoniae in community-acquired pneumonia in adults. Of 981 patients with pneumococcal pneumonia, 46 (4.7 %) had levofloxacin-nonsusceptible S. pneumoniae, of whom 39 evaluable cases were included in the analysis. All cases were from Korea, Taiwan, and Hong Kong. Among patients with levofloxacin-susceptible S. pneumoniae, 490 controls were selected based on patient country. Of the 39 cases of levofloxacin-nonsusceptible pneumococcal pneumonia, 23 (59.0 %) were classified as healthcare-associated, while 164 (33.5 %) of the 490 controls of levofloxacin-susceptible S. pneumoniae (P?=?0.001) were classified as healthcare-associated. Multivariate analysis showed that previous treatment with fluoroquinolones, cerebrovascular disease, and healthcare-associated infection were significantly associated with levofloxacin-nonsusceptible pneumococcal pneumonia (all P?<?0.05). Levofloxacin-nonsusceptible pneumococci pose an important new public health threat in our region, and more information on the emergence and spread of these resistant strains will be necessary to prevent spread throughout the population.     

A genetic risk score for hypertension associates with the risk of ischemic stroke in a Swedish case–control study

Genetic risk scores (GRS), summing up the total effect of several single-nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS based on 29 SNPs discovered by genome-wide association studies and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other ‘traditional risk factors'', also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case–control study. Twenty-nine SNPs were genotyped in 3677 stroke cases and 2415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the combined sample, and separately for the three studies. After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the combined sample (OR (95% CI) 1.086 (1.029–1.147) per SD increase in the GRS P=0.003) with similar trends in all three samples: LSR (1.050 (0.967–1.140); P=0.25), MDC (1.168 (1.060–1.288); P=0.002) and SAHLSIS (1.124 (0.997–1.267); P=0.055). Measures of risk discrimination and reclassification improved marginally using the GRS. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case–control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.     

Risk factors for MRSA infection in companion animals: Results from a case–control study within Germany

Increasing numbers of companion animals suffering from infections with methicillin-resistant Staphylococcus aureus (MRSA) have been reported in the recent past. These infections are of particular concern because of the limited treatment options for MRSA and their transferability to humans. Since MRSA lineages isolated from infected companion animals often mirror typical human epidemic strains circulating in the same region, successful strategies to combat MRSA need strong and coordinated efforts from both, the human and the veterinary field according to the “One Health” concept. Hence, to identify potential risk factors related to MRSA infections in dogs, cats and horses, a case–control study was conducted, including data on 106 MRSA-infected animal patients as cases and 102 MSSA-infected animals as controls, originating from 155 different veterinary settings within Germany. Demographic data on animal patients, patient history and administration of antibiotics as well as practice/clinic specific parameters were assessed as putative risk factors. Multivariable logistic regression identified the following variables as risk factors for MRSA infection compared to MSSA infection: number of employees working at the veterinary setting (n > 10; p < 0.001), antibiotic treatment prior to sampling (systemic: p = 0.002; local: p = 0.049, both: p = 0.011) and surgical site infection (p < 0.001). Spa typing revealed predominantly clonal complexes well-known for hospital-associated lineages spreading in human health-care settings in Germany (CC5 and CC22) for isolates of dog and cat origin. CC398-MRSA dominated among equine isolates, a CC that was described as a nosocomial pathogen in equine clinical settings before.     

COVID-19 in patients with pre-existing chronic liver disease – predictors of outcomes

Coronavirus disease 2019 (COVID-19) has affected patients with pre-existing chronic liver disease (CLD) in various ways. The maximum impact was seen on patients with underlying cirrhosis who have shown to have poor clinical outcomes in the form of increased risk of hepatic decompensation, acute-on-chronic liver failure, and even mortality. It is of paramount importance to identify various factors which are associated with unfavorable outcomes for prognostication and making informed management strategy. Many factors have been evaluated in different studies in patients with underlying CLD. Some of these factors include the severity of underlying chronic liver disease, comorbid conditions, age, and severity of COVID-19. Overall, the outcomes are not fav-orable in patients with cirrhosis as evidenced by data from various studies. The main purpose of this review is to identify the predictors of adverse clinical outcomes including mortality in patients with CLD for risk stratification, prognostication, and appropriate clinical management.     

Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case–control study with meta-analysis

Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) variants leads to carcinogenesis by affecting DNA synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C, and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case-control study of 239 bladder cancer cases and 250 cancer-free controls, we found that the MTHFR 677TT genotype was statistically significantly associated with an increased risk of bladder cancer compared with the 677CC genotype (OR = 2.06, 95% CI = 1.16-3.64). Furthermore, the TA haplotype was associated with a significantly increased bladder cancer risk (OR = 1.38, 95% CI = 1.05-1.81) than was the most common haplotype, CA (e.g., CA denotes MTHFR 677C -1298A). We also found that the combined genotypes with 4-6 variant (risk) alleles (i.e., MTHFR 677T, 1298A, and MS 2756G alleles) were associated with an increased risk of bladder cancer (OR = 1.62, 95% CI = 1.03-2.53) compared with those with 0-3 variants, and this increased risk was more pronounced among subgroup of older people (OR = 1.71, 95% CI = 1.03-2.83). A meta-analysis of seven studies did not show a significant risk of bladder cancer in the MTHFR polymorphisms. The MTHFR polymorphisms and their haplotypes appear to jointly contribute to risk of bladder cancer.     

Primary Sjögren's syndrome and occupational risk factors: A case–control study

ObjectivesA case–control study was carried out to investigate the relation between primary Sjögren's syndrome (pSS) and occupational exposure.MethodsOne hundred seventy five cases of pSS followed up into the internal medicine departments of three French university hospitals from 2010 to 2013 were included. For each case, two age and gender matched controls were selected during the same period in the same departments. Occupational exposure was assessed retrospectively by industrial hygienists and occupational practitioners. Exposure to occupational factors such as organic solvents or silica was investigated using semiquantitative estimates of exposure. An exposure score was calculated for each subject based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained, taking into account all periods of employment.ResultsSignificant associations with pSS were observed for dichloromethane (OR 9.28, 95%CI 2.60–33.03), perchlorethylene (OR 2.64, 95%CI 1.20–5.77) chlorinated solvents (OR 2.95, 95%CI 1.77–4.93), benzene (OR 3.30, 95%CI 1.07–10.26), toluene (OR 4.18 95%CI 1.41–12.43), white spirit (OR 3.60, 95%CI 1.39–9.33), aromatic solvents (OR 3.03, 95%CI 1.41–6.50) and any types of solvents (OR 2.76, 95%CI 1.70–4.47). Risk of pSS was significantly associated with a high cumulative exposure score of occupational exposure to toluene (OR 4.69, 95%CI 1.42–15.45), white spirit (OR 3.30, 95%CI 1.07–10.26), aromatic solvents (OR 2.50, 95%CI 1.06–5.91) and any types of solvents (OR 2.25, 95%CI 1.20–4.22).ConclusionThis work suggests the influence of occupational risk factors in the occurrence of pSS.     

Polymorphisms in DNA repair genes and breast cancer risk in Russian population: a case–control study

Genetic variation in DNA repair genes can alter an individual’s capacity to repair damaged DNA and influence the risk of cancer. We tested seven polymorphisms in DNA repair genes XRCC1, ERCC2, XRCC3, XRCC2, EXOI and TP53 for a possible association with breast cancer risk in a sample of 672 case and 672 control Russian women. An association was observed for allele A of the polymorphism XRCC1 (R399Q) rs25487 (co-dominant model AA vs. GG: OR 1.76, P = 0.003; additive model OR 1.28, P = 0.005; dominant model: OR 1.29, P = 0.03; recessive model OR 1.63, P = 0.008). Allele T of the polymorphism ERCC2 (D312N) rs1799793 was also associated with breast cancer risk (co-dominant model TT vs. CC: OR 1.43, P = 0.04; additive model OR 1.21, P = 0.02; dominant model: OR 1.30, P = 0.02), but the association became insignificant after applying Bonferroni correction. No association with breast cancer was found for the remaining SNPs. In summary, our study provides evidence that polymorphisms in DNA repair genes may play a role in susceptibility to breast cancer in the population of ethnical Russians.     

Pneumocystis jirovecii pneumonia in renal transplant recipients occurring after discontinuation of prophylaxis: a case–control study

A case–control study was conducted to identify risk factors for Pneumocystis jirovecii pneumonia (PCP) in renal transplant recipients. Eleven cases of PCP were matched with 22 controls. Cases occurred a median of 18 months after transplantation, and none of the recipients was receiving prophylaxis. Univariate analysis showed that graft rejection, duration of steroid use, use of mammalian target of rapamycin (mTOR) inhibitors and lymphocytopenia at the time of prophylaxis discontinuation were risk factors for PCP. In the multivariate model, only graft rejection (OR 8.66, p 0.017) remained significantly associated with PCP. In patients with a history of graft rejection, PCP prophylaxis should be maintained, especially among those with lymphocytopenia.     

Presence of diarrhea associated with better outcomes in patients with COVID-19 – A prospective evaluation

PurposeGastrointestinal (GI) manifestations have been well documented in patients with coronavirus disease 2019 (COVID-19), but its clinical impact on the course of the disease is debatable. Majority of the available data is retrospective, and hence this prospective study was planned to study the impact of GI symptoms on COVID-19 outcome.MethodsAll COVID-19 patients admitted in a tertiary care centre from August–October 2020 were screened and patients without pre-existing GI diseases were included. A detailed history of the various symptoms including duration was documented. Various baseline laboratory investigations and inflammatory markers were conducted as per the protocol. Patients with and without diarrhea were compared for the various disease outcome parameters.ResultsOf the 244 patients screened, 203 patients (128 males; 63.1%) were included. Respiratory symptoms alone were present in 49 (24.1%), GI symptoms alone in 20 (9.9%) and 117 (57.6%) had both. Overall GI symptoms was noted in 137 (67.5%) cases with the commonest being diarrhea (61; 30.0%). Patients with both respiratory and any GI symptoms showed a lower trend towards need for mechanical ventilation (12.2% vs 7.7%; p ?= ?0.35) and mortality (10.2% vs 4.3%; p ?= ?0.14) compared to respiratory symptoms alone, although not statistically significant. Patients with diarrhea (n ?= ?61) had no mortality (0% vs 7.7%; p ?= ?0.036) or need for mechanical ventilation and shorter hospital stay compared to those who did not have diarrhea.ConclusionGI symptoms are frequent in patients with SARS-CoV-2 infection and the commonest is diarrhea. Diarrhea is a harbinger of better outcome with lower mortality among COVID-19 positive patients.     

Combination therapy with ciprofloxacin and third-generation cephalosporin versus third-generation cephalosporin monotherapy in Escherichia coli meningitis in infants: a multicentre propensity score–matched observational study

ObjectivesEscherichia coli is the second cause of bacterial meningitis in neonates. Despite the use for 35 years of third-generation cephalosporins (3GCs), high morbidity and mortality rates with E. coli meningitis continue to occur. Because ciprofloxacin has good microbiologic activity against E. coli and good penetration in cerebrospinal fluid and brain, some authors have suggested adding ciprofloxacin to a 3GC regimen. The objective of this study was to assess combining 3GCs with ciprofloxacin versus 3GCs alone in a cohort of infants with E. coli meningitis.MethodsWe included all cases of E. coli meningitis diagnosed in infants <12 months of age that were prospectively collected through the French paediatric meningitis surveillance network between 2001 and 2016. The main outcome was the proportion of short-term neurologic complications with versus without ciprofloxacin. The analysis was conducted retrospectively by multivariable regression and propensity score (PS) analysis.ResultsAmong the 367 infants enrolled, 201 (54.8%) of 367 had ciprofloxacin and 3GC cotreatment and 166 (45.2%) of 367 only a 3GC. Median age and weight were 15 days (range, 1–318 days) and 3.42 kg (range, 0.66–9.4 kg). A total of 86 (23.4%) of 367 infants presented neurologic complications (seizures, strokes, empyema, abscesses, hydrocephalus, arachnoiditis); 57 received ciprofloxacin cotreatment. Complications were associated with ciprofloxacin cotreatment on multivariable analysis (odds ratio (OR) = 1.9; 95% confidence interval (CI), 1.1–3.4) and PS analysis (OR = 1.9; 95% CI, 1.1–3.3). Mortality rate did not differ with and without ciprofloxacin: 22 (10.9%) of 201 versus 16 (9.6%) of 166 deaths (OR = 0.7; 95% CI, 0.3–1.6; PS analysis).ConclusionsCiprofloxacin added to 3GCs at least offers no advantage for neurologic outcome and mortality in infants with E. coli meningitis.