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Gut microbiota composition has been implicated in surgical site complications after colorectal cancer surgery. Antibiotics affect gut microbiota, but evidence for a role in surgical site complications is inconclusive. We aimed to investigate use of prescription antibiotics during the years before surgery in relation to the risk of surgical site infections, including anastomotic leakage, within 30 days after surgery. Cardiovascular/neurological complications and the urinary antiseptic methenamine hippurate, for which there is no clear link with the microbiota, were used as negative controls. We conducted a patient cohort study using complete population data from Swedish national registers between 2005 and 2020. The final study population comprised 26,527 colon cancer and 12,312 rectal cancer cases with a 4.5 year exposure window. In colon cancer patients, antibiotics use was associated with a higher risk of surgical site infections (adjusted odds ratio (aOR) for any versus no use = 1.20, 95% confidence interval (CI) 1.10–1.33) and anastomotic leakage in particular (aOR =1.19, 95% CI 1.03–1.36), both with dose–response relationships for increasing cumulative antibiotics use (Ptrend = <0.001 and Ptrend = 0.047, respectively). Conversely, associations in rectal cancer patients, as well as for the negative controls cardiovascular/neurological complications and methenamine hippurate, were null. In conclusion, prescription antibiotics use up to 4.5 years before colorectal cancer surgery is associated with a higher risk of surgical site infections, including anastomotic leakage, after colon cancer but not rectal cancer surgery. These findings support a role for antibiotics-induced intestinal dysbiosis in surgical site infections.

BACKGROUND: Antibiotics use is associated with higher colorectal cancer risk, but little is known regarding any potential effects on survival.

METHODS: We conducted a nationwide cohort study, using complete-population data from Swedish national registers between 2005 and 2020, to investigate prediagnostic prescription antibiotics use in relation to survival in colorectal cancer patients.

RESULTS: We identified 36,061 stage I-III and 11,242 stage IV colorectal cancer cases diagnosed between 2010 and 2019. For stage I-III, any antibiotics use (binary yes/no variable) was not associated with overall or cancer-specific survival. Compared with no use, moderate antibiotics use (total 11-60 days) was associated with slightly better cancer-specific survival [adjusted HR (aHR) = 0.93; 95% confidence interval (CI), 0.86-0.99)], whereas very high use (>180 days) was associated with worse survival [overall survival (OS) aHR = 1.42; 95% CI, 1.26-1.60, cancer-specific survival aHR = 1.31; 95% CI, 1.10-1.55]. In analyses by different antibiotic types, although not statistically significant, worse survival outcomes were generally observed across several antibiotics, particularly macrolides and/or lincosamides. In stage IV colorectal cancer, inverse relationships between antibiotics use and survival were noted.

CONCLUSIONS: Overall, our findings do not support any substantial detrimental effects of prediagnostic prescription antibiotics use on cancer-specific survival after colorectal cancer diagnosis, with the possible exception of very high use in stage I-III colorectal cancer. Further investigation is warranted to confirm and understand these results.

IMPACT: Although the study findings require confirmation, physicians probably do not need to factor in prediagnostic prescription antibiotics use in prognosticating patients with colorectal cancer.

BACKGROUND: Antibiotics use may increase colorectal cancer (CRC) risk by altering the gut microbiota, with suggestive evidence reported. Our study aims to investigate antibiotics use in relation to subsequent CRC risk.

METHODS: This is a nationwide, population-based study with a matched case-control design (first primary CRC cases and 5 matched, cancer-free controls). Complete-population data, extracted from Swedish national registers for the period 2005-2016, were used to calculate odds ratios and 95% confidence intervals.

RESULTS: We included 40 545 CRC cases and 202 720 controls. Using the full dataset, we found a positive association between more frequent antibiotics use and CRC, excluding antibiotics prescribed within 2 years of diagnosis attenuated results toward the null. In site-specific analyses, excluding the 2-year washout, the positive association was confined to the proximal colon (adjusted odds ratio for very high use vs no use = 1.17, 95% confidence interval = 1.05 to 1.31). For rectal cancer, an inverse association, which appears to be driven by women, was observed. Quinolones and sulfonamides and/or trimethoprims were positively associated with proximal colon cancer, whereas a more general inverse association, across antibiotics classes, was observed for rectal cancer. We found no association between methenamine hippurate, a urinary tract antiseptic not affecting the gut microbiota, and CRC risk.

CONCLUSIONS: This register-based study covering the entire population of Sweden found a robust association between antibiotics use and higher risk of proximal colon cancer and an inverse association with rectal cancer in women. This study strengthens the evidence from previous investigations and adds important insight into site-specific colorectal carcinogenesis.

Background: This study aimed to investigate what impact the COVID-19 pandemic and its associated restrictions had on Chlamydia trachomatis and Neisseria gonorrhoeae infections in Sweden, Denmark and Norway, countries with very different governmental strategies for handling this pandemic.

Methods: Retrospective analysis of data collected via requests to Swedish regions and to health authorities in Denmark and Norway. The data were collected for the years 2018–2020 and the data from Sweden were more detailed.

Results: When the pandemic restrictions were installed in 2020, the number of reported chlamydia cases decreased. The decline was most pronounced in Norway 10.8% (2019: n = 28,446; 2020: n = 25,444) while it was only 3.1% in Denmark (2019: n = 35,688; 2020: n = 34,689) and 4.3% in Sweden (2019: n = 34,726; 2020: n = 33,339). Nucleic acid amplifications tests for chlamydia decreased in Sweden (10%) and Norway (18%) in 2020 compared to 2019, while in Denmark a 21% decrease was noted in April 2020 but thereafter increased to a higher level than 2019. The number of reported gonorrhoea cases decreased in Sweden (17%) and in Norway (39%) in 2020 compared to 2019, while a 21% increase was noted in Denmark.

Conclusions: Pandemic restrictions had an impact on the number of reported chlamydia infections in all three countries, but only temporarily and did not seem to be correlated to the restriction levels. The number of reported gonorrhoea infections in Sweden and Norway significantly decreased but not in Denmark. Pandemic restrictions appear to have had a limited effect on the spread of chlamydia and gonorrhoea.

Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC₅₀) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced.

Chlamydia trachomatis is a strict intracellular bacterium that causes sexually transmitted infections and eye infections that can lead to lifelong sequelae. Treatment options are limited to broad-spectrum antibiotics that disturb the commensal flora and contribute to selection of antibiotic-resistant bacteria. Hence, development of novel drugs that specifically target C. trachomatis would be beneficial. 2-Pyridone amides are potent and specific inhibitors of Chlamydia infectivity. The first-generation compound KSK120 inhibits the developmental cycle of Chlamydia, resulting in reduced infectivity of progeny bacteria. Here, we show that the improved, highly potent second-generation 2-pyridone amide KSK213 allowed normal growth and development of C. trachomatis, and the effect was only observable upon reinfection of new cells. Progeny elementary bodies (EBs) produced in the presence of KSK213 were unable to activate transcription of essential genes in early development and did not differentiate into the replicative form, the reticulate body (RB). The effect was specific to C. trachomatis since KSK213 was inactive in the closely related animal pathogen Chlamydia muridarum and in Chlamydia caviae. The molecular target of KSK213 may thus be different in C. trachomatis or nonessential in C. muridarum and C. caviae. Resistance to KSK213 was mediated by a combination of amino acid substitutions in both DEAD/DEAH RNA helicase and RNase III, which may indicate inhibition of the transcriptional machinery as the mode of action. 2-Pyridone amides provide a novel antibacterial strategy and starting points for development of highly specific drugs for C. trachomatis infections.

The pharyngeal mucosa can be colonized with bacteria that have potential to cause pharyngotonsillitis. By the use of culturing techniques and PCR, we aimed to assess the prevalence of bacterial pharyngeal pathogens among healthy adolescents and young adults. We performed a cross-sectional study in a community-based cohort of 217 healthy individuals between 16 and 25 years of age. Samples were analyzed for Group A streptococci (GAS), Group C/G streptococci (SDSE), Fusobacterium necrophorum, and Arcanobacterium haemolyticum. Compared to culturing, the PCR method resulted in more frequent detection, albeit in most cases with low levels of DNA, of GAS (20/217 vs. 5/217; p < 0.01) and F. necrophorum (20/217 vs. 8/217; p < 0.01). Culturing and PCR yielded similar rates of SDSE detection (14/217 vs. 12/217; p = 0.73). Arcanobacterium haemolyticum was rarely detected (3/217), and only by PCR. Overall, in 25.3% (55/217) of these healthy adolescents and young adults at least one of these pathogens was detected, a rate that is higher than previously described. Further studies are needed before clinical adoption of PCR-based detection methods for pharyngeal bacterial pathogens, as our findings suggest a high incidence of asymptomatic carriage among adolescents and young adults without throat infections.

Mucormycosis is a life threatening infection in patients with haematological disease. We introduced a Mucorales-PCR and an aggressive, multidisciplinary management approach for mucormycosis during 2016-2017 and evaluated patient outcomes in 13 patients diagnosed and treated in 2012-2019. Management principle: repeated surgical debridement until biopsies from the resection margins were clean as defined by negative Blankophor microscopy, Mucorales-PCR (both reported within 24 h), and cultures. Cultured isolates underwent EUCAST E.Def 9.3.1 susceptibility testing. Antifungal therapy (AFT) (mono/combination) combined with topical AFT (when possible) was given according to the minimal inhibitory concentration (MIC), severity of the infection, and for azoles, specifically, it was guided by therapeutic drug monitoring. The outcome was evaluated by case record review. All patients underwent surgery guided by diagnostic biopsies from tissue and resection margins (195 samples in total). Comparing 2012-2015 and 2016-2019, the median number of patients of surgical debridements was 3 and 2.5 and of diagnostic samples: microscopy/culture/PCR was 3/3/6 and 10.5/10/10.5, respectively. The sensitivity of microscopy (76%) and Mucorales-PCR (70%) were similar and microscopy was superior to that of culture (53%; p = 0.039). Initial systemic AFT was liposomal amphotericin B (n = 12) or posaconazole (n = 1) given as monotherapy (n = 4) or in combination with isavuconazole/posaconazole (n = 3/6) and terbinafine (n = 3). Nine patients received topical amphotericin B. All received isavuconazole or posaconazole consolidation therapy (n = 13). Mucormycosis related six month mortality was 3/5 in 2012-2015 and 0/7 patients in 2016-2019 (one patient was lost for follow-up). Implementation of combination therapy (systemic+topical AFT/combination systemic AFT) and aggressive surgical debridement guided by optimised diagnostic tests may improve the outcome of mucormycosis in haematologic patients.

Chlamydia trachomatis infections are a global health problem and new approaches to treat C. trachomatis with drugs of high specificity would be valuable. A library of substituted ring fused 2-pyridones has been synthesized and evaluated for their ability to attenuate C. trachomatis infectivity. In vivo pharmacokinetic studies were performed, with the best candidates demonstrating that a C8-methylsulfonamide substituent improved pharmacokinetic properties important for oral administration. C8-Methyl sulfonamide analogue 30 inhibited C. trachomatis infectivity in low micromolar concentrations. Further pharmacokinetic evaluation at an oral dose of 10 mg kg(-1) showed an apparent bioavailability of 41%, compared to C8-cyclopropyl and -methoxy analogues which had negligible oral uptake. In vitro ADME (absorption, distribution, metabolism and excretion) testing of solubility and Caco-2 cell permeability revealed that both solubility and permeability is greatly improved with the C8-methyl sulfonamide 30, effectively moving it from BCS (Biopharmaceutical Classification System) class IV to II.

Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12–24 h), Day 2 (at 36–48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6–1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery.