Helicobacter pylori resistance to antibiotics before and after treatment: Incidence of eradication failure.

BACKGROUND: Increasing prevalence of antibiotic resistance especially to clarithromycin and metronidazole has been observed in Helicobacter pylori (H. pylori). AIM: To characterize the antimicrobial resistance pattern of H. pylori before and after treatment in a cohort of patients accumulated over a period of 15 years after an unsuccessful eradication treatment had been given comparing sensitivity data from patients with newly diagnosed H. pylori infection. A specific objective was to look for resistance to levofloxacin. MATERIAL AND METHODS: Total of 50 patients newly diagnosed for H. pylori infection treated with omeprazole and amoxicillin/clarithromycin and 42 H pylori treatment-resistant patients treated with omeprazole and amoxicillin/levofloxacin were enrolled in this study. Cultures including antibiotic sensitivity testing were conducted according to standard laboratory routines and thus also in keeping with a European study protocol using E-test gradient strips or disc diffusion methods. RESULTS: Clarithromycin resistance was more frequently observed in the H. pylori resistant group than in newly diagnosed H. pylori group (39% versus 11%). Regarding metronidazole the distribution was 70% versus 38%, and 8% versus 12% were resistant to tetracycline. No resistance was observed for amoxicillin. After re-treatment of patients belonging to the H. pylori treatment-resistant group, just two patient strains were recovered of which one harbored metronidazole resistance. In the group of newly diagnosed H. pylori, seven patients were culture positive by control after treatment. Two and three patient strains showing resistance to clarithromycin and metronidazole, respectively. None of the strains in our material was classified as resistant to amoxicillin and levofloxacin. Whereas 12% was resistant to tetracycline in the newly diagnosed before treatment. CONCLUSION: Clarithromycin resistance was more frequent in the H. pylori treatment-resistant group than strains from patients with newly diagnosed H. pylori infection. No resistance was observed to amoxicillin and levofloxacin. In such cases Therefore levofloxacin may be used provided in vitro sensitivity testing confirms applicability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05019586.

Clinical characterization of Helicobacter pylori infected patients 15 years after unsuccessful eradication.

BACKGROUND AND AIMS: Patients that have failed therapy for Helicobacter pylori (H. pylori) infection are incompletely characterized. The aim of this study was to characterize a H. pylori treatment resistant cohort compared to the cohorts of newly diagnosed, earlier eradicated and non-infected. MATERIAL AND METHODS: Patients were selected from routine referrals to the Endoscopy units at three different Norwegian hospitals. In all four cohorts, gastric biopsies were scored according to the Sydney classification, and symptoms according to the Gastrointestinal Symptom Rating Scale score, including sub-scores for upper gastrointestinal symptoms and functional bowel symptoms. Patients in the H. pylori resistant group were treated with a triple therapy regimen that consisted of levofloxacin, amoxicillin and a proton pump inhibitor. RESULTS: We included 185 patients, 42 H. pylori treatment resistant, 50 newly diagnosed, 61 previously H. pylori eradicated and 32 never infected. The treatment-resistant cohort had higher scores for upper gastrointestinal symptoms and functional bowel symptoms compared to the other groups except for the group being never H. pylori infected. The H. pylori resistant patients had lower Sydney scores than patients with newly diagnosed H. pylori infection. The triple combination showed a high efficacy of 91% to eradicate H. pylori. CONCLUSIONS: Patients with treatment-resistant H. pylori infection had more gastrointestinal symptoms, but a lower Sydney score than patients with newly diagnosed infection. A treatment regimen including levofloxacin showed a high efficacy in eradicating H. pylori in patients that previously had failed eradication treatment.

Helicobacter pylori in early childhood and asthma in adolescence.

OBJECTIVE: An inverse effect of Helicobacter pylori (H. pylori) on the occurrence of asthma is debated and early acquisition of H. pylori may be important. We analyzed sera from 197 children from Environment and Childhood Asthma (ECA) study in Oslo for Helicobacter pylori (H. pylori) at 2 and 10 years, and symptoms and signs of asthma at 16 years of age. RESULTS: While 16.4% of children who were H. pylori negative at 2 and 10 years had current asthma at 16 years, none of the 12 children who were H. pylori positive at 2 years of age had asthma at the age of 16 years, regardless of H. pylori status at 10 years. This trend for less current asthma in children who were H. pylori positive at 2 years compared to persistent or transient negative status at 10 years was not statistically significant, probably due to low number of H. pylori positive children at 2 years of age. Acquisition of H. pylori in school age did not appear to influence the risk of current asthma. Much larger prospective studies are probably required to document whether or not early H. pylori infection may be involved in the risk of asthma development in later childhood.

Maternal Colonization with Group B Streptococcus Is Associated with an Increased Rate of Infants Transferred to the Neonatal Intensive Care Unit.

BACKGROUND: Streptococcus agalactiae (group B Streptococcus, GBS) is the most common cause of early neonatal infection, but restricting the diagnosis to culture-positive infants may underestimate the burden of GBS disease. Our objective was to determine whether maternal GBS colonization was associated with an increased risk of transfer of term infants to the neonatal intensive care unit (NICU) and, if so, to estimate the incidence of probable early-onset GBS disease. METHODS: We conducted a prospective cohort study of 1,694 term infants whose mothers had vaginal-rectal swabs collected at delivery. Data collected on each mother and infant included demographics, clinical findings and laboratory investigations. The medical staff were unaware of the maternal GBS colonization status. RESULTS: A total of 26% of the mothers were colonized. Infants born to colonized mothers did not differ from infants born to non-colonized mothers with respect to birth weight or Apgar score. Altogether, 30 (1.8%) of the term infants were transferred to the NICU. Only 1 infant born to a colonized mother had culture-positive early-onset GBS disease. Infants born to colonized mothers were more than 3 times as likely to be transferred to the NICU compared to infants of non-colonized mothers (3.6 vs. 1.1%; OR 3.4, 95% CI 1.6-6.9, p = 0.001); 5 infants of colonized mothers had probable GBS disease with tachypnoea and raised C-reactive protein (3.0/1,000 live term births). CONCLUSIONS: Maternal GBS colonization is associated with increased risk of transfer to the NICU in term infants. The burden of neonatal GBS disease may be greater than indicated by the number of culture-positive cases.

Comparison of PCR and serotyping of Group B Streptococcus in pregnant women: the Oslo GBS-study.

Streptococcus agalactiae (GBS) is a leading cause of invasive neonatal infection. Serotyping of GBS is important in following epidemiological trends and vaccine development. Capsular serotyping of GBS by latex agglutination has been the predominant typing method, but more recently capsular genotyping has been introduced as an alternative method. The purpose of this study was to compare the relative performance of these methods in a contemporary population of pregnant women. We typed isolates from an unselected population of 426 colonized women at delivery using latex agglutination and a combination of four PCR methods. Antibiotic resistance was tested in 449 isolates. Capsular genotyping gave a result in all except three of 426 isolates. Fifty-nine of 426 isolates could not be typed by latex agglutination. Agreement between serotyping and genotyping was shown in 303 (71.1%) of the isolates. 10.2% of the isolates were resistant to erythromycin, 9.6% to clindamycin, 76.6% to tetracycline and none to penicillin. In conclusion, a substantial proportion of the colonizing strains were non-typeable by serotyping, but typeable by genotyping. This suggests that a diagnostic genotyping strategy is preferable to serotyping of the GBS polysaccharide capsule in colonized, pregnant women.

Age-related differences in symptoms, diagnosis and prognosis of bacteremia.

BACKGROUND: Elderly patients are at particular risk for bacteremia and sepsis. Atypical presentation may complicate the diagnosis. We studied patients with bacteremia, in order to assess possible age-related effects on the clinical presentation and course of severe infections. METHODS: We reviewed the records of 680 patients hospitalized between 1994 and 2004. All patients were diagnosed with bacteremia, 450 caused by Escherichia coli and 230 by Streptococcus pneumoniae. Descriptive analyses were performed for three age groups (< 65 years, 65-84 years, ≥ 85 years). In multivariate analyses age was dichotomized (< 65, ≥ 65 years). Symptoms were categorized into atypical or typical. Prognostic sensitivity of CRP and SIRS in identifying early organ failure was studied at different cut-off values. Outcome variables were organ failure within one day after admission and in-hospital mortality. RESULTS: The higher age-groups more often presented atypical symptoms (p <0.001), decline in general health (p=0.029), and higher in-hospital mortality (p<0.001). The prognostic sensitivity of CRP did not differ between age groups, but in those ≥ 85 years the prognostic sensitivity of two SIRS criteria was lower than that of three criteria. Classical symptoms were protective for early organ failure (OR 0.67, 95% CI 0.45-0.99), and risk factors included; age ≥ 65 years (OR 1.65, 95% CI 1.09-2.49), comorbid illnesses (OR 1.19, 95% CI 1.02-1.40 per diagnosis), decline in general health (OR 2.28, 95% CI 1.58-3.27), tachycardia (OR 1.50, 95% CI 1.02-2.20), tachypnea (OR 3.86, 95% CI 2.64-5.66), and leukopenia (OR 4.16, 95% CI 1.59-10.91). Fever was protective for in-hospital mortality (OR 0.46, 95% CI 0.24-0.89), and risk factors included; age ≥ 65 years (OR 15.02, 95% CI 3.68-61.29), ≥ 1 comorbid illness (OR 2.61, 95% CI 1.11-6.14), bacteremia caused by S. pneumoniae (OR 2.79, 95% CI 1.43-5.46), leukopenia (OR 4.62, 95% CI 1.88-11.37), and number of early failing organs (OR 3.06, 95% CI 2.20-4.27 per failing organ). CONCLUSIONS: Elderly patients with bacteremia more often present with atypical symptoms and reduced general health. The SIRS-criteria have poorer sensitivity for identifying organ failure in these patients. Advanced age, comorbidity, decline in general health, pneumococcal infection, and absence of classical symptoms are markers of a poor prognosis.

Helicobacter pylori infection and severe hyperemesis gravidarum among immigrant women in Norway: a case-control study.

OBJECTIVE: To study associations between Helicobacter pylori exposure and severe hyperemesis gravidarum (HG) among immigrant women in Norway by exploring IgG seropositivity and H. pylori antigens in faeces. Additionally, we investigated whether cytotoxin-associated gene A product (CagA) and vacuolating cytotoxin A (VacA) seropositivity modulated this association. STUDY DESIGN: An institution-based case-control study among immigrant women in Norway was performed at Ullevål and Akershus University Hospitals in September 2005-December 2007. Blood samples were used to explore IgG, CagA and VacA seropositivity, and faecal samples were used to explore the presence of antigens. Multiple logistic regressions were used to study associations between HG and H. pylori exposure. RESULTS: The sample comprised 170 women: 62 cases and 108 controls. The observed proportion of IgG seropositive women did not differ between cases and controls. Neither IgG seropositivity nor CagA and VacA seropositivity were significantly associated with HG. For IgG positive and CagA and VacA negative women, the crude OR was 1.26 (95% CI: 0.57-2.82). For those being IgG positive and CagA and VacA positive, the crude OR was 0.82 (0.40-1.68). Adjustment for confounding factors, such as maternal age, body mass index and earlier HG, did not change the results. Additional adjustment for faecal antigens did not change the conclusions regarding these associations. Likewise, the crude OR for H. pylori antigens was not statistically significant. Adjustment for confounders and IgG seropositivity did not change this result. CONCLUSIONS: This study did not find H. pylori exposure to be significantly associated with severe HG among immigrant women in Norway. This was regardless of whether H. pylori exposure was investigated by IgG seropositivity, CagA and VacA seropositivity or by the presence of H. pylori antigens in faeces. These results may indicate that the association between H. pylori and HG is weaker than previously expected, particularly in populations with high prevalence of H. pylori infection.

Resistance rates of metronidazole and other antibacterials in Helicobacter pylori from previously untreated patients in Norway.

The aim of the study was to describe the antimicrobial resistance rate of Helicobacter pylori isolated from previously untreated patients in Norway, including the application of two different methods for the determination of metronidazole susceptibility. Altogether 102 isolates obtained in 2008 and 2009 from previously untreated patients suspected of H. pylori related disease, were examined applying a standardized European study protocol. The activity of amoxicillin, tetracycline, clarithromycin, metronidazole, rifabutin and levofloxacin was recorded after an incubation period of 72-96 h in a microaerobic atmosphere. Strains resistant to metronidazole were re-examined for metronidazole resistance applying anaerobic conditions for the first 24 h. None of the isolates were resistant to amoxicillin or tetracycline, whereas 5, 9% were resistant to clarithromycin and 22, 5% resistant to metronidazole tested conventionally. Applying local standards the metronidazole resistance rate fell to 7, 8%, highlighting the importance of the methodology applied for metronidazole susceptibility testing.

Appropriate time for test-of-cure when diagnosing gonorrhoea with a nucleic acid amplification test.

Culture is commonly regarded as the gold standard for diagnosis of Neisseria gonorrhoeae. However, nucleic acid amplification tests (NAATs) have rapidly replaced culture for diagnostics in many settings. The aim of the present study was to investigate the appropriate time for test-of-cure (TOC) when NAATs are used for diagnosis of gonorrhoea. In total, 30 patients (28 men and 2 women) provided urethral, cervical, rectal or pharyngeal specimens for TOC. All included patients, except one who did not return for second TOC before day 19, tested negative within 2 weeks after treatment with cefixime 400 mg × 1. Antimicrobial susceptibility testing showed that 68% of the culture-positive strains were resistant to ciprofloxacin. Thus, the recommended empirical treatment with ciprofloxacin in Norway should be changed immediately. TOC can be performed 2 weeks after treatment when NAATs are used for diagnosis of gonorrhoea.

Comparison of PCR with culture applied on nasopharyngeal and throat swab specimens for the detection of Bordetella pertussis.

An in-house nested polymerase chain reaction (PCR) was prospectively compared with culture for Bordetella pertussis detection in 435 nasopharyngeal and/or throat swabs from 304 patients. One hundred specimens - 21% of nasopharyngeal swabs and 25% of throat swabs - were PCR- and/or culture-positive. Seventy percent of positive nasopharyngeal samples and 44% of positive throat samples were culture-positive.

[Tigecycline--a new antibiotic]. / Tigesyklin--et nytt antibiotikum.

Tigecycline belongs to a new class of antimicrobial agents, the glycylcyclines, which are structurally derived from tetracyclines. It is effective against both gram positive and gram negative bacteria, aerobes and anaerobes and bacteria that have developed resistance against the classic tetracyclines. Although there is an increased risk for serious adverse events, tigecycline is important for treatment of patients with complicated infections of moderate severity where other antimicrobials cannot be used.

A multidrug-resistant, methicillin-susceptible strain of Staphylococcus aureus from a neonatal intensive care unit in Oslo, Norway.

Over a 6-month period in 2008, approximately 15% of all Staphylococcus aureus isolates from our neonatal intensive care unit were resistant to penicillin, gentamicin, erythromycin and clindamycin. Extended antibiotic susceptibility testing and molecular profiling revealed an outbreak of an S. aureus strain with a rare susceptibility pattern for a Scandinavian setting.

Helicobacter pylori infection and hyperemesis gravidarum: a systematic review and meta-analysis of case-control studies.

OBJECTIVE: To summarize the evidence from epidemiological studies examining the association between Helicobacter pylori infection and hyperemesis gravidarum. DESIGN: Systematic review and meta-analysis of case-control studies. MATERIAL AND METHODS: We searched the Medline/PubMed, Embase, Cinahl, ISI Web of Science and Biological Abstracts databases from 1966 to 17 June 2008 and finally Google Scholar. A total of 25 case-control studies were identified. Both fixed-effect and random-effect models were used to synthesize the results of individual studies. The Cochran Q, tau(2) of between-study variance and index of heterogeneity (I(2)) were used to evaluate heterogeneity. Heterogeneity between studies was examined by subgroup and random effect meta-regression analyses. Publication bias was evaluated. RESULTS: Publication bias was not observed. The random model pooled estimate was odds ratio = 3.32, 95 % confidence interval (CI): 2.25-4.90. A high heterogeneity was pinpointed (I(2) = 80 %, 95 % CI: 65-89). Subgroup analysis and meta-regression showed a weaker association in studies with a clear definition of hyperemesis gravidarum compared to studies without this condition, and weaker association in recent studies compared to earlier studies. Meta-regression showed that these two study characteristics explained 40% of heterogeneity between studies. CONCLUSIONS: Exposure to H. pylori appears to be associated with an increased risk of hyperemesis gravidarum. The residual heterogeneity might have different reasons. Given the high prevalence of H. pylori, the public health consequence of H. pylori with regard to hyperemesis gravidarum may be important.

Bacteria, biofilm and honey: a study of the effects of honey on 'planktonic' and biofilm-embedded chronic wound bacteria.

Chronically infected wounds are a costly source of suffering. An important factor in the failure of a sore to heal is the presence of multiple species of bacteria, living cooperatively in highly organized biofilms. The biofilm protects the bacteria from antibiotic therapy and the patient's immune response. Honey has been used as a wound treatment for millennia. The components responsible for its antibacterial properties are now being elucidated. The study aimed to determine the effects of different concentrations of 'Medihoney' therapeutic honey and Norwegian Forest Honey 1) on the real-time growth of typical chronic wound bacteria; 2) on biofilm formation; and 3) on the same bacteria already embedded in biofilm. Reference strains of MRSE, MRSA, ESBL Klebsiella pneumoniae and Pseudomonas aeruginosa were incubated with dilution series of the honeys in microtitre plates for 20 h. Growth of the bacteria was assessed by measuring optical density every 10 min. Growth curves, biofilm formation and minimum bactericidal concentrations are presented. Both honeys were bactericidal against all the strains of bacteria. Biofilm was penetrated by biocidal substances in honey. Reintroduction of honey as a conventional wound treatment may help improve individual wound care, prevent invasive infections, eliminate colonization, interrupt outbreaks and thereby preserve current antibiotic stocks.

Helicobacter pylori infection and Hyperemesis gravidarum. An institution-based case-control study.

BACKGROUND: The etiology of Hyperemesis gravidarum (HG) is unclear. To test the hypothesis of an association between Helicobacter pylori infection and HG, an institution-based case-control study was performed at Aker University Hospital (AUH) during 1994-1999. MATERIAL AND METHOD: From the same source population, 244 incident cases of HG and 244 pregnant women free of the disease (controls) were consecutively identified. RESULTS: H. pylori were noted in 105 cases and 58 control subjects. The presence of H. pylori increased the risk of HG more than two fold (OR = 2.42, 95% CI: 1.64-3.57, P < 0.001). This association was much stronger in Africans as compared to non-Africans (OR = 5.26, 95% CI: 1.04-26.57 vs. OR = 1.67, 95% CI: 1.07-2.61) after controlling for the confounding effect of maternal age. A gradient effect of exposure to H. pylori, determined by presence of specific IgG antibody in serum, and increased frequency of HG was present in Africans (test for linear trend P = 0.05) and non-Africans (test for linear trend P = 0.004). CONCLUSION: These results indicate that H. pylori increase the risk of HG with a dose-response pattern and stronger in Africans.

Clinical validation of a real-time polymerase chain reaction detection of Neisseria gonorrheae porA pseudogene versus culture techniques.

BACKGROUND: Diagnosing Neisseria gonorrheae using nucleic acid amplification tests (NAATs) might increase the sensitivity, compared to cultivation. However, using NAATs has also been problematic mainly due to the close genetic relationships between different Neisseria species, resulting in false positive diagnoses. This study was conducted to clinically validate a previously published real-time polymerase chain reaction (PCR) method targeting the porA pseudogene in N. gonorrheae in comparison to culture techniques. METHODS: In total, 360 samples, urethra (n = 109), rectum (n = 84), pharynx (n = 119), and cervix (n = 48) from 185 males and 57 females, were analyzed using porA pseudogene PCR and cultivation. Sequencing of the entire porA pseudogene and the 16S rRNA gene were used to resolve discrepant results. RESULTS: Of the 360 samples, 37 were positive by both culture and PCR, however, the PCR identified 15 additional confirmed positive samples. The PCR method showed a sensitivity, specificity, positive predictive value, and negative predictive value of 100% in a preselected population. The preselected population had a true gonorrhea prevalence of 17.4%. CONCLUSIONS: The present porA pseudogene real-time PCR comprises a valuable supplement to the traditional culture techniques for diagnosis of N. gonorrheae, especially for samples from extragenital sites such as pharynx and rectum.

Susceptibility to daptomycin, quinupristin-dalfopristin and linezolid and some other antibiotics in clinical isolates of methicillin resistant and methicillin sensitive S.aureus from the Oslo area.

Our study compared the susceptibility of 136 clinical isolates of Staphylococcus aureus and 119 multidrug-resistant Staphylococcus aureus (MRSA) isolates from Oslo to a range of antibiotics, including the novel antibiotics quinupristin-dalfopristin, linezolid and daptomycin. All isolates were susceptible to daptomycin, linezolid and quinupristin-dalfopristin, although a subgroup was less susceptible to the latter. There was no linkage between reduced susceptibility to daptomycin, linezolid or quinupristin-dalfopristin and resistance to other classes of antimicrobials. In addition, MRSA strains from 2004 have become more sensitive to fucidin and rifampicin. The results can be used to evaluate the appropriateness of breakpoints and to define a baseline for monitoring possible future emergence of resistance to daptomycin, quinupristin-dalfopristin and linezolid in Staphylococcus aureus in Norway.