Risk Factors for Relapse in Acute Bacterial Prostatitis: the Impact of Antibiotic Regimens

Acute bacterial prostatitis; Antibiotic resistance; RelapseProstatitis bacteriana aguda; Resistencia a los antibióticos; RecaídaProstatitis bacteriana aguda; Resistència als antibiòtics; RecaigudaThe aim of the study was to analyze the risk factors for relapse in patients with acute bacterial prostatitis (ABP), focusing on the impact of different antibiotic regimens. We conducted an observational study of all patients diagnosed with ABP (irritative and/or obstructive urinary symptoms, temperature of >37.8°C, and the presence of bacteriuria in urine culture, in the absence of data suggesting pyelonephritis) from January 2017 to December 2018. The main outcome was relapse. We performed a multivariate analysis to identify the risk factors associated with relapse. A propensity score with inverse weighting was applied to attenuate antibiotic selection bias. We included 410 patients. The mean age was 68 years; 28.8% had diabetes mellitus, and 61.1% benign prostatic hyperplasia. The most common isolated bacteria were Escherichia coli (62.4%) and Klebsiella spp. (10%). The overall resistance rate was 39.5% to quinolones. The mortality rate was 1.2%, and the relapse rate was 6.3%. The only independent risk factor for relapse was inadequate antibiotic therapy (odds ratio [OR] 12.3; 95% confidence interval [95% CI], 3.5 to 43.1). When the antibiotic was modified according to the susceptibility pattern, the rates of relapse were 1.8% in those treated with ciprofloxacin, 3.6% with intravenous beta-lactam, 9.3% with co-trimoxazole, and 9.8% with oral (p.o.) beta-lactam (P = 0.03). Treatment with oral beta-lactam (OR, 5.3; 95% CI, 1.2 to 23.3) and co-trimoxazole (OR, 4.9; 95% CI, 1.1 to 23.2) were associated with a risk of relapse. In this large real-life observational study, a significantly higher relapse rate was observed when antibiotic treatment was inadequate. When the antibiotic was tailored, quinolones and intravenous beta-lactams had a lower relapse rate than co-trimoxazole and oral beta-lactams. IMPORTANCE In the manuscript, we report a large series of acute bacterial prostatitis cases and describe data about the etiology, antibiotic resistance rate, and outcome, specially focused on the risk factors for relapse. We found high rates of resistance to the most frequently used antibiotics and a high relapse rate in patients whose treatment was not adjusted according to their microbiological susceptibility. We did not observe differences, though, in mortality or relapse according to appropriate or inappropriate empirical treatment. What is new in this article is the different relapse rates observed depending upon the definitive adequate antibiotic used. Quinolones and intravenous (i.v.) beta-lactam have lower rates of relapse (1.8% and 3.6%, respectively) compared to co-trimoxazole and oral (p.o.) beta-lactam (3.3% and 9.8%, respectively). Clinicians should carefully choose an adequate antibiotic for definitive ABP treatment depending on the results of microbiological isolation, using quinolones as the first option. Whenever quinolones cannot be administered, i.v. beta-lactams seem to be the second-best option.The Spanish Network for Research in Infectious Diseases is supported by AGAUR grant 2017 SGR 1055, Generalitat de Catalunya. No other financial support was received for this work

Single-locus-sequence-based typing of the mgpB gene reveals transmission dynamics in mycoplasma genitalium

Sexually transmitted infections (STIs) by Mycoplasma genitalium are a major problem worldwide, especially given their marked and rapid propensity for developing antimicrobial resistance. Since very few treatment options exist, clinicians face an important challenge in the management of the infection. In this scenario, little is known regarding the transmission dynamics of M. genitalium and the epidemiology of antimicrobial resistance. This mgpB-based molecular typing study, conducted among 54 asymptomatically infected individuals prospectively recruited from an STI screening service, reveals two distinct epidemiological clusters that significantly correlate with sexual conduct in heterosexuals and men who have sex with men (MSM), respectively. This well-defined structuration suggests the presence of two independent sexual networks with little connectivity between them. On the other hand, the study demonstrates the multiclonal feature of the emergence of antibiotic resistance in M. genitalium to both macrolides and fluoroquinolones. The high prevalence of macrolide resistance in M. genitalium among MSM, influenced by dense network connectivity and strong antibiotic selective pressure, may correspond to allodemics affecting other STIs such as gonorrhea, syphilis and enteric pathogens. Collaterally, the structural and functional impact of mutations in the mgpB gene, encoding the major adhesin P140 (MgpB), may require further investigation.This work was partially supported by an “Ayuda SEIMC” grant from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC)

Neisseria gonorrhoeae: monitorització de la sensibilitat antimicrobiana, estudi de la dinàmica poblacional i caracterització molecular de les resistències

La gonorrea es la segona infecció de transmissió sexual d’etiologia bacteriana més prevalent. És un important problema de Salut Pública, no només per l’augment de la seva incidència, sinó també perquè Neisseria gonorrhoeae ha desenvolupat resistència a tots els antibiòtics al llarg dels anys. És necessari establir i mantenir programes de control per tal de monitoritzar la sensibilitat antimicrobiana i així mantenir actualitzades les guies de tractament. A més, estudis d’epidemiologia molecular també podrien contribuir a entendre millor els patrons de transmissió de la infecció gonocòccica en la població i detectar xarxes sexuals d’alt risc. Els objectius d’aquesta Tesi són: 1. comparar el rendiment diagnòstic del cultiu bacteriològic enfront de les tècniques d’amplificació d’àcids nucleics en la infecció gonocòccica; 2. monitoritzar la sensibilitat antimicrobiana del gonococ a l’àrea de Barcelona i estudiar els mecanismes moleculars implicats en el desenvolupament de resistència a les cefalosporines; 3. analitzar la dinàmica poblacional dels gonococs en funció del perfil de resistència i de l’orientació sexual dels pacients. Es van comparar els resultats del cultiu i de la PCR (Versant CT/GC DNA 1.0 assay), de juliol a desembre del 2012. La concordança va ser del 96,9%. Del 3,1% dels discordants, gairebé el 90% va ser deguts a la falta de sensibilitat del cultiu. La sensibilitat, l’especificitat, el valor predictiu positiu i el valor predictiu negatiu del cultiu van ser de 86,2%, 99,8%, 99,2%, i 96,7%; i de la PCR de 98,7%, 100%, 100% i 99,7%, respectivament. Tot i que actualment els laboratoris utilitzen la PCR pel diagnòstic de rutina, en els laboratoris de referència una aproximació eficient seria realitzar la PCR i paral·lelament també el cultiu en els pacients simptomàtics. Es va monitoritzar la sensibilitat del gonococ del 1 d’agost del 2012 al 31 de juliol del 2016 i es van estudiar els determinants genètics relacionats amb la resistència a les cefalosporines. El percentatge de soques amb sensibilitat intermitja o resistencia a la penicil.lina va oscilar entre el 65% al 2012 i el 93,7% al 2016. Al voltant del 50% són resistents a ciprofloxacino. Més del 60% de les soques presentaven una CMI de ceftriaxona ≤0,016 µg/mL. El percentatge de resistència a cefixima va ser superior al de ceftriaxona. La taxa de resistència a azitromicina va ser aproximadament del 5%. Més del 60% de les soques van presentar CMIs de gentamicina entre 3 i 4 µg/mL i el 90% CMIs de fosfomicina compreses entre 3 i 16 µg/mL, constituint-se en possibles alternatives terapèutiques. El factor més important pel desenvolupament de resistència a les cefalosporines són els canvis en el gen penA (patró mosaic XXXIV i substitució en A501). El genogrup G1407 és significativament més prevalent entre les soques amb SD que entre les sensibles. El G2400 és el segon en prevalença entre les soques amb SD i presenta una associació estadísticament significativa amb la mutació A501T de l’al·lel XXXVI. Es van caracteritzar 111 soques aïllades de pacients amb diferent orientació sexual. La taxa de resistència va ser superior en les soques de pacients heterosexuals, sent la cefixima (p=0.0159) i el ciprofloxacino (p=0.002) significativament més resistents. Els STs més prevalents van ser ST2400, ST2992, i ST5793; i els genogrups més prevalents els G1407, G2992, i G2400. Es va observar una associació estadísticament significativa entre els pacients homosexuals i els genogrups G2400 (p=0.0005) i G2992 (p=0.0488), i entre els heterosexuals i el genogrup G1407 (p=0.0002).Gonorrhoea is the second most prevalent sexually transmitted infection caused by bacteria. It is a serious public health problem, not only because of the increasing incidence but also because Neisseria gonorrhoeae has developed resistance to all antibiotics used over the years. Control programs are needed in order to monitor the antimicrobial susceptibility and to keep the treatment guidelines updated. Molecular epidemiology studies could be useful for a better understanding of gonococci transmission patterns and for indentifying high-risk sexual networks. The objectives of this thesis are: 1. To compare the diagnostic yield of culture with that of polymerase chain reaction (PCR) in gonococcal infection; 2. To monitor antimicrobial susceptibility of gonococci in Barcelona and to study the molecular mechanisms involved in the development of resistance to cephalosporins; 3. To compare the antimicrobial susceptibility and genotypes of strains of Neisseria gonorrhoeae isolated from men who have sex with men (MSM) and from heterosexuals. We compared the results of culture and PCR (Versant CT / GC DNA 1.0 assay) from July to December 2012. The agreement was 96.9%. 3.1% of the results were discordant, and almost 90% of these were due to the lack of sensitivity of the culture. The sensitivity, specificity, positive predictive value, and negative predictive value for culture were 86.2%, 99.8%, 99.2%, and 96.7%, and for PCR, 98.7%, 100%, 100% and 99.7%, respectively. In laboratories where antimicrobial susceptibility is monitored, an effective approach would be to perform culture in addition to PCR in symptomatic patients. Antimicrobial susceptibility was monitored from August 1st 2012 to July 31st 2016 and molecular mechanisms related to cephalosporins resistance were studied. The rate of strains with decreased susceptibility or resistance to penicillin ranged from 65% in 2012 to 93.7% in 2016. About 50% were resistant to ciprofloxacin. More than 60% of the strains showed a ceftriaxone MIC ≤0,016 µg / mL. The rate of resistance to cefixime was higher than ceftriaxone, with a significant increase in 2013. The rate of azithromycin resistance was approximately 5%. More than 60% of the strains had gentamicin MIC between 3 and 4 µg / mL and 90% had fosfomycin MIC between 3 and 16 µg / mL. These antibiotics can be possible therapeutic alternatives, although more studies are needed. The most important factor for cephalosporins resistance development are the changes in the gene penA (XXXIV mosaic pattern and aminoacid substitution in A501). The genogroups G1407 is significantly more prevalent among the strains with decreased susceptibility to cephalosporins. The G2400 is the second most prevalent among these strains and presents a statistically significant association with the A501T mutation in XXXVI allele. 111 isolates from patients with different sexual orientation were characterized. The resistance rate was higher in strains isolated from heterosexual patients, being cefixime (p = 0.0159) and ciprofloxacin (p = 0.002) significantly more resistant. The STs most frequent were ST2400, ST2992 and ST5793; and the genogroups most frequent were G1407, G2992 and G2400. There was a statistically significant association between homosexuals patients and genogroups G2400 (p = 0.0005) and G2992 (p = 0.0488), and between heterosexuals and genogroups G1407 (p = 0.0002)

Neisseria gonorrhoeae : monitorització de la sensibilitat antimicrobiana, estudi de la dinàmica poblacional i caracterització molecular de les resistències /

BibliografiaLa gonorrea es la segona infecció de transmissió sexual d'etiologia bacteriana més prevalent. És un important problema de Salut Pública, no només per l'augment de la seva incidència, sinó també perquè Neisseria gonorrhoeae ha desenvolupat resistència a tots els antibiòtics al llarg dels anys. És necessari establir i mantenir programes de control per tal de monitoritzar la sensibilitat antimicrobiana i així mantenir actualitzades les guies de tractament. A més, estudis d'epidemiologia molecular també podrien contribuir a entendre millor els patrons de transmissió de la infecció gonocòccica en la població i detectar xarxes sexuals d'alt risc. Els objectius d'aquesta Tesi són: 1. comparar el rendiment diagnòstic del cultiu bacteriològic enfront de les tècniques d'amplificació d'àcids nucleics en la infecció gonocòccica; 2. monitoritzar la sensibilitat antimicrobiana del gonococ a l'àrea de Barcelona i estudiar els mecanismes moleculars implicats en el desenvolupament de resistència a les cefalosporines; 3. analitzar la dinàmica poblacional dels gonococs en funció del perfil de resistència i de l'orientació sexual dels pacients. Es van comparar els resultats del cultiu i de la PCR (Versant CT/GC DNA 1.0 assay), de juliol a desembre del 2012. La concordança va ser del 96,9%. Del 3,1% dels discordants, gairebé el 90% va ser deguts a la falta de sensibilitat del cultiu. La sensibilitat, l'especificitat, el valor predictiu positiu i el valor predictiu negatiu del cultiu van ser de 86,2%, 99,8%, 99,2%, i 96,7%; i de la PCR de 98,7%, 100%, 100% i 99,7%, respectivament. Tot i que actualment els laboratoris utilitzen la PCR pel diagnòstic de rutina, en els laboratoris de referència una aproximació eficient seria realitzar la PCR i paral·lelament també el cultiu en els pacients simptomàtics. Es va monitoritzar la sensibilitat del gonococ del 1 d'agost del 2012 al 31 de juliol del 2016 i es van estudiar els determinants genètics relacionats amb la resistència a les cefalosporines. El percentatge de soques amb sensibilitat intermitja o resistencia a la penicil·lina va oscilar entre el 65% al 2012 i el 93,7% al 2016. Al voltant del 50% són resistents a ciprofloxacino. Més del 60% de les soques presentaven una CMI de ceftriaxona ≤0,016 µg/mL. El percentatge de resistència a cefixima va ser superior al de ceftriaxona. La taxa de resistència a azitromicina va ser aproximadament del 5%. Més del 60% de les soques van presentar CMIs de gentamicina entre 3 i 4 µg/mL i el 90% CMIs de fosfomicina compreses entre 3 i 16 µg/mL, constituint-se en possibles alternatives terapèutiques. El factor més important pel desenvolupament de resistència a les cefalosporines són els canvis en el gen penA (patró mosaic XXXIV i substitució en A501). El genogrup G1407 és significativament més prevalent entre les soques amb SD que entre les sensibles. El G2400 és el segon en prevalença entre les soques amb SD i presenta una associació estadísticament significativa amb la mutació A501T de l'al·lel XXXVI. Es van caracteritzar 111 soques aïllades de pacients amb diferent orientació sexual. La taxa de resistència va ser superior en les soques de pacients heterosexuals, sent la cefixima (p=0.0159) i el ciprofloxacino (p=0.002) significativament més resistents. Els STs més prevalents van ser ST2400, ST2992, i ST5793; i els genogrups més prevalents els G1407, G2992, i G2400. Es va observar una associació estadísticament significativa entre els pacients homosexuals i els genogrups G2400 (p=0.0005) i G2992 (p=0.0488), i entre els heterosexuals i el genogrup G1407 (p=0.0002).Gonorrhoea is the second most prevalent sexually transmitted infection caused by bacteria. It is a serious public health problem, not only because of the increasing incidence but also because Neisseria gonorrhoeae has developed resistance to all antibiotics used over the years. Control programs are needed in order to monitor the antimicrobial susceptibility and to keep the treatment guidelines updated. Molecular epidemiology studies could be useful for a better understanding of gonococci transmission patterns and for indentifying high-risk sexual networks. The objectives of this thesis are: 1. To compare the diagnostic yield of culture with that of polymerase chain reaction (PCR) in gonococcal infection; 2. To monitor antimicrobial susceptibility of gonococci in Barcelona and to study the molecular mechanisms involved in the development of resistance to cephalosporins; 3. To compare the antimicrobial susceptibility and genotypes of strains of Neisseria gonorrhoeae isolated from men who have sex with men (MSM) and from heterosexuals. We compared the results of culture and PCR (Versant CT / GC DNA 1.0 assay) from July to December 2012. The agreement was 96.9%. 3.1% of the results were discordant, and almost 90% of these were due to the lack of sensitivity of the culture. The sensitivity, specificity, positive predictive value, and negative predictive value for culture were 86.2%, 99.8%, 99.2%, and 96.7%, and for PCR, 98.7%, 100%, 100% and 99.7%, respectively. In laboratories where antimicrobial susceptibility is monitored, an effective approach would be to perform culture in addition to PCR in symptomatic patients. Antimicrobial susceptibility was monitored from August 1st 2012 to July 31st 2016 and molecular mechanisms related to cephalosporins resistance were studied. The rate of strains with decreased susceptibility or resistance to penicillin ranged from 65% in 2012 to 93.7% in 2016. About 50% were resistant to ciprofloxacin. More than 60% of the strains showed a ceftriaxone MIC ≤0,016 µg / mL. The rate of resistance to cefixime was higher than ceftriaxone, with a significant increase in 2013. The rate of azithromycin resistance was approximately 5%. More than 60% of the strains had gentamicin MIC between 3 and 4 µg / mL and 90% had fosfomycin MIC between 3 and 16 µg / mL. These antibiotics can be possible therapeutic alternatives, although more studies are needed. The most important factor for cephalosporins resistance development are the changes in the gene penA (XXXIV mosaic pattern and aminoacid substitution in A501). The genogroups G1407 is significantly more prevalent among the strains with decreased susceptibility to cephalosporins. The G2400 is the second most prevalent among these strains and presents a statistically significant association with the A501T mutation in XXXVI allele. 111 isolates from patients with different sexual orientation were characterized. The resistance rate was higher in strains isolated from heterosexual patients, being cefixime (p = 0.0159) and ciprofloxacin (p = 0.002) significantly more resistant. The STs most frequent were ST2400, ST2992 and ST5793; and the genogroups most frequent were G1407, G2992 and G2400. There was a statistically significant association between homosexuals patients and genogroups G2400 (p = 0.0005) and G2992 (p = 0.0488), and between heterosexuals and genogroups G1407 (p = 0.0002)

Oral quinolones versus intravenous β-lactam for the treatment of acute focal bacterial nephritis : a retrospective cohort study

Altres ajuts: acords transformatius de la UABBackground: Evidence regarding the best antibiotic regimen and the route of administration to treat acute focal bacterial nephritis (AFBN) is scarce. The aim of the present study was to compare the effectiveness of intravenous (IV) β-lactam antibiotics versus oral quinolones. Methods: This is a retrospective single centre study of patients diagnosed with AFBN between January 2017 and December 2018 in Hospital Universitari Vall d'Hebron, Barcelona (Spain). Patients were identified from the diagnostic codifications database. Patients treated with oral quinolones were compared with those treated with IV β-lactam antibiotics. Therapeutic failure was defined as death, relapse, or evolution to abscess within the first 30 days. Results: A total of 264 patients fulfilled the inclusion criteria. Of those, 103 patients (39%) received oral ciprofloxacin, and 70 (26.5%) IV β-lactam. The most common isolated microorganism was Escherichia coli (149, 73.8%) followed by Klebsiella pneumoniae (26, 12.9%). Mean duration of treatment was 21.3 days (SD 7.9). There were no statistical differences regarding therapeutic failure between oral quinolones and IV β-lactam treatment (6.6% vs. 8.7%, p = 0.6). Out of the 66 patients treated with intravenous antibiotics, 4 (6.1%) experienced an episode of phlebitis and 1 patient (1.5%) an episode of catheter-related bacteraemia. Conclusions: When susceptible, treatment of AFBN with oral quinolones is as effective as IV β-lactam treatment with fewer adverse events

Methicillin-resistant and methicillin-sensitive Staphylococcus aureus in pork industry workers, Catalonia, Spain

Methicillin-resistant S. aureus (MRSA) especially ST398, is a zoonotic agent. This study aimed to determine the prevalence of methicillin-susceptible S. aureus (MSSA) and MRSA among workers in the pork production chain. 659 workers associated with 123 pig farms, livestock transporters, one pig slaughterhouse, pork transporters and 23 pork butcheries were studied for S. aureus recovery, and all isolates were characterized (antibiotic resistance, MLST and spa -typing). The prevalence of S. aureus was 35.5%, 75.6% of isolates being MRSA. The prevalence of MRSA was 68.7% (149/217) among pig farm, 33.9% (19/56) livestock transporters, 2.9% (9/306) slaughterhouse, 0% in pork transporters (0/36) and butchery workers (0/44). Of the 234 S. aureus -positive workers, 100% (149/149) of pig farm workers, 82.6% (19/23) of livestock transporters, and 16.4% (9/55) of slaughterhouse workers carried MRSA isolates (p < 0.001). Of the workers who had contact with live swine, 61.8% (178/288) were S. aureus -positive, MRSA being detected in 96.1% of cases (p < 0.001). The most frequent lineage among MRSA were: ST398 (97.7%; 173/177) and ST1 (1.7%; 3/177); and among MSSA were ST30 (19.2%; 11/57) and ST5 (10.5%; 6/57). The most frequent spa -types among MRSA were t011 (93.8%, 166/177) and t1451 (2.25%, 4/177), and among MSSA: t084 (10.5%, 6/57) and t021 (7.0%, 4/57). All MRSA isolates showed resistance to tetracycline, 92.7% to clindamycin, 81.9% to erythromycin and 40.1% to cotrimoxazole. Pig industry workers having occupational contact with live animals present a high risk of colonization of MRSA, especially by MRSA-ST398. Prevention measures should be intensified in any employment sector involving live animals