Helicobacter pylori eradication in Western Australia using novel quadruple therapy combinations.

BACKGROUND: Helicobacter pylori eradication rates with standard triple therapy are declining worldwide. The optimal management of H. pylori is evolving and new treatment combinations for antibiotic resistant H. pylori strains are required, especially for patients with penicillin allergy. AIM: To review the effectiveness of alternative antibiotic combinations and necessity of pre-antibiotic sensitivity testing. METHODS: A total of 310 consecutive patients who had failed at least one course of standard 7-day triple therapy initially prescribed by their physicians were included in this study between year 2007 and 2011. Antibiotics were prescribed based on pre-antibiotic sensitivity tests and, if any, patient's allergy to penicillin. RESULTS: In 98.7% of the patients' samples, H. pylori was successfully cultured. The proportion resistant to clarithromycin and metronidazole was 94.1% and 67.6% respectively, with 65% resistant to both. For the in-house primary quadruple therapy, with Proton pump inhibitor, Amoxicillin, Rifabutin and Ciprofloxacin (PARC), H. pylori was successfully eradicated in 95.2% of patients. For patients allergic to amoxicillin, an alternative quadruple therapy using Proton pump inhibitor, Bismuth subcitrate, Rifabutin and Ciprofloxacin (PBRC) gave an eradication rate of 94.2%. Patients needing alternative salvage therapy were given novel personalised combinations consisting of bismuth, rifabutin, tetracycline or furazolidone; the eradication rate was 73.8%. CONCLUSIONS: Patients who present with antibiotic resistant H. pylori can be confidently treated with PARC, PBRC or other personalised salvage therapies. These regimens can be used when treatment options are limited by penicillin allergy. Pre-treatment H. pylori antibiotic sensitivity tests contributed to the high eradication rate in this study.

Discrepancy between minimal inhibitory concentration to enrofloxacin and mutations present in the quinolone-resistance determining regions of Mycoplasma gallisepticum field strains.

Molecular characterization of the quinolone-resistance determining regions (QRDRs) of DNA gyrase and topoisomerase IV in 93 Mycoplasma gallisepticum field strains isolated in different geographic regions revealed discrepancies between minimal inhibitory concentration values and presence of amino acid substitutions within the QRDRs of GyrA and ParC in 9/93 (10%) strains. This may delimitate applicability of a gene-based assay to detect fluoroquinolone resistance in this avian pathogen.

Human recombinant lactoferrin is ineffective in the treatment of human Helicobacter pylori infection.

BACKGROUND: Lactoferrin, a multifunctional glycoprotein, is known to have anti-microbial actions. Bovine lactoferrin and recombinant human lactoferrin have been shown to inhibit Helicobacter pylori, and more recently recombinant human lactoferrin was found to significantly increase the eradication rate of H. pylori when added to standard triple therapy. AIM: To determine the efficacy, safety and tolerability of recombinant human lactoferrin as a therapy in suppressing or eliminating H. pylori infection in subjects with minimal upper gastrointestinal symptoms who have not previously been treated. SUBJECTS AND METHODS: Nine healthy subjects with minimal upper gastrointestinal symptoms and a positive urea breath test were recruited. None of the volunteers had previously been treated for H. pylori. Subjects received 5 x 1.0 g human recombinant lactoferrin daily for 5 or 14 days. Breath tests were repeated during therapy and shortly after to check for eradication. The safety and tolerability of the drug were assessed by physical examination, by monitoring adverse events, and clinical laboratory evaluation. RESULTS: No conversion of the urea breath test from positive to negative was observed and there was no consistent change in urea breath test count to indicate a possible suppression of H. pylori. CONCLUSION: Lactoferrin, given as a single agent, does not eradicate H. pylori infection.

Helicobacter pylori is not the cause of sudden infant death syndrome (SIDS).

OBJECTIVES: The cause of sudden infant death syndrome (SIDS) is unknown, but our previous hypothesis proposed that Helicobacter pylori could be a causative organism. In this study, we aimed to test this hypothesis by examining gastric and tracheal tissues from a prospective cohort of SIDS infants and re-examining previously studied paraffin-fixed tissues for H. pylori. METHODS: Fresh gastric antral and trachea specimens obtained at postmortem from nine consecutive new cases of SIDS in Perth, Western Australia were studied prospectively. Tissues were evaluated for H. pylori by rapid urease test (CLOtest), bacterial culture, histology (hematoxylin and eosin, Warthin-Starry Silver, and immmunoperoxidase staining), and polymerase chain reaction (PCR). The latter two tests were also used for the re-examination of paraffin-embedded specimens from infants who died from SIDS (n = 17) and other non-SIDS causes (n = 7) in Kansas City, Missouri. RESULTS: Specimens from nine consecutive SIDS infants in Western Australia showed no evidence of H. pylori by any analyses. In the paraffin-embedded gastric and trachea specimens from Missouri, rod and coccoid-shaped bacteria were seen histologically in 33.3% of the specimens, but these were not typical H. pylori. Upon analysis by PCR, "H. pylori DNA" was detected in 53% (9/17) of SIDS samples versus 57% (4/7) in non-SIDS samples. In all cases the immunoperoxidase stain was negative, suggesting that PCR either 1) gave false positive results in this type of potentially contaminated postmortem specimen or 2) H. pylori DNA was indeed present but not increased in prevalence in SIDS infants. CONCLUSIONS: H. pylori is unlikely to be an etiological agent in SIDS.

Bacteriology and taxonomy of Helicobacter pylori.

As the scientific community approaches the twentieth anniversary of the first isolation of H. pylori, it appears that despite the wealth of articles published in journals throughout the world every month, there are still many unanswered questions about the microbiology of this bacterium and others in the genus Helicobacter.

Culture of Helicobacter pylori from a gastric string may be an alternative to endoscopic biopsy.

Helicobacter pylori was isolated from a swallowed string from 32 of 33 adult subjects (97%) with selective culture media. With this method, antibiotic susceptibility testing and molecular epidemiology studies of H. pylori can be carried out without the need for the collection of specimens by endoscopic biopsy.

Accurate diagnosis of Helicobacter pylori. Polymerase chain reaction tests.

Although PCR has improved considerably the sensitivity of the diagnosis of H. pylori infection, many studies have not shown conclusively the full potential of PCR in clinical diagnosis. In daily clinical practice, PCR does not have to be performed to establish H. pylori infection. PCR is still classified primarily as a research technique in the Helicobacter field. PCR or similar technology will expand in the future when automation and commercialized kits are available to most laboratories. The development of a noninvasive PCR test may prove useful because it may lead ultimately to the determination of the source and route of transmission of this important pathogen.

Successful recovery of H. pylori from rapid urease tests (CLO tests).

OBJECTIVE: Culture of Helicobacter pylori (H. pylori) and the determination of its antibiotic susceptibility is of increasing importance with the rise in numbers of antibiotic-resistant strains. The aim of this study was to determine whether H. pylori could be successfully isolated from antral biopsies used in Rapid Urease Tests (CLOtests) in clinical practice. METHODS: Antral biopsies from patients undergoing endoscopy were inserted into the gel of CLOtests to determine the H. pylori status of the patients. If the CLOtest was positive at the end of the endoscopy session, it was kept at ambient temperature until processed. In the laboratory, biopsies were removed from the gel and cultured on selective and nonselective media. In an attempt to enhance the recovery rate of H. pylori, a subset of positive CLOtests were kept at 4 degrees C from the time that the color change was noted until the removal of the biopsy. RESULTS: One hundred and forty-one positive CLOtests were studied at times between 1 h and 6 h postendoscopy. Culture success was 93% in the 1st hour but fell off sharply after 2 h (p < 0.001). Isolation was also improved if positive CLOtests were stored at 4 degrees C and plated out within 4 h (p < 0.001). CONCLUSIONS: H. pylori can be successfully cultured from biopsies in CLOtests kept at room temperature within 2 h or within 4 h if kept at 4 degrees C. Thus the antral biopsy in the CLOtest can be usefully retrieved when, in the light of the CLOtest result, the physician wishes to obtain both culture and antibiotic sensitivity results.

An outbreak of respiratory disease in horses associated with Mycoplasma felis infection.

Lower respiratory tract disease developed in a group of racehorses in training between two and six years of age. Disease was observed in 22 of 25 horses for which full records were available. Seroconversion to Mycoplasma felis was demonstrated by indirect haemagglutination assay in 19 of 22 paired sera and high titres (> or = 64) were found in convalescent sera from the three remaining horses. Evidence of respiratory viral infection was confined to seroconversions to equine herpesvirus-4 in two of the horses. Tracheal wash samples, taken from four horses with visibly increased tracheal mucopus, contained more than 10(4) colony forming units/ml M felis and high proportions of neutrophils. This is the first description of an outbreak of lower respiratory tract disease in horses in training associated with M felis infection.

In vitro susceptibilities of recent field isolates of Mycoplasma hyopneumoniae and Mycoplasma hyosynoviae to valnemulin (Econor), tiamulin and enrofloxacin and the in vitro development of resistance to certain antimicrobial agents in Mycoplasma hyopneumoniae.

The in vitro activities of valnemulin (Econor) and two other antimicrobial agents were determined against recent field strains of Mycoplasma hyopneumoniae and Mycoplasma hyosynoviae using a broth microdilution method. Valnemulin showed exceptional activity against M hyopneumoniae (MIC90 0.0005 microgram ml-1) and M hyosynoviae (MIC range 0.0001 microgram ml-1 to 0.00025 microgram ml-1) field strains. Tiamulin was 100-fold less active (MIC90 0.05 microgram ml-1) and enrofloxacin 20-fold less active (MIC90 0.01 microgram ml-1) than valnemulin against M hyopneumoniae field isolates and 20-fold to 25-fold less active (MIC range 0.0025 microgram ml-1 to 0.005 microgram ml-1) and 400-fold to 500-fold less active (MIC range 0.05 microgram ml-1 to 0.1 microgram ml-1) respectively against M hyosynoviae field isolates. No significant resistance developed to valnemulin or tiamulin in the type strain of M hyopneumoniae (strain J) or in a recent field isolate (MEVT G23) exposed to 10 in vitro passages in broths containing these antibiotics. Only slight resistance to oxytetracycline was observed. High resistance to tylosin developed in both M hyopneumoniae strains within five to seven in vitro passages in tylosin-containing broth. Providing that similar results are obtained in vivo under field conditions, valnemulin may well prove to be effective in the treatment of enzootic pneumonia and acute polyarthritis in pigs.

Growth characteristics of V factor-independent transformants of Haemophilus influenzae.

Haemophilus influenzae is a V factor-dependent species. A plasmid conferring V factor independence in Haemophilus parainfluenzae and Haemophilus ducreyi was transferred to plasmid-free H. influenzae Rd by DNA transformation. The growth characteristics of the transformants in a complex and a chemically defined medium were compared, and the ability of several exogenous pyridine nucleotides and precursors to support growth was examined. Although the transformants appeared to be V factor independent in a complex medium, in a chemically defined medium they exhibited both V factor-dependent and nicotinamide-dependent growth. Because of the inability of the plasmid-free H. influenzae Rd to utilize nicotinamide for growth, it was concluded that the genes conferring this function were plasmid linked. Our results indicate that the V factor requirement, as it is presently defined, is not suitable to serve as a definitive taxonomic criterion for species determination in the family Pasteurellaceae.

Plasmid-mediated NAD independence in Haemophilus parainfluenzae.

The location of the genes coding for NAD independence in four unusual clinical isolates of Haemophilus parainfluenzae was determined by transferring these genes to plasmid-free Haemophilus influenzae Rd by transformation and analysing transformants for the presence of plasmids by agarose gel electrophoresis. All NAD-independent transformants were found to carry a single plasmid species. The plasmids, originally harboured by the four H. parainfluenzae isolates recovered from unrelated sources, were of the same size (5.25 kb). Spontaneous reversion to NAD dependence occurred with a low frequency (0.1 to 0.2% of the progeny of a single clone) in both H. parainfluenzae and H. influenzae Rd. The revertants had lost this small plasmid. Mitomycin C exhibited a plasmid 'curing' effect with a frequency of 'curing' of between 1 and 6% of the surviving clones. It was concluded that the genes conferring NAD independence were located on the small 5.25 kb plasmid.

Subacute heart rupture and hemopericardium following acute myocardial infarction: report of successful treatment and ten year follow-up.

Hemopericardium complicating acute myocardial infarction generally has a poor prognosis. Two cases of this complication, one due to subacute rupture of the free left ventricular wall, are reported. Both patients are still alive and well ten years after urgent surgical intervention. Good long-term results are possible in this condition if diagnosis and surgical intervention are not delayed.

Postinfarction cardiac rupture.

This paper records an experience of 42 cases of cardiac rupture or syndromes simulating rupture. These include free wall rupture, hemopericardium without rupture, septal rupture associated with free wall rupture, pseudoaneurysm, and septal rupture. These groups constitute a series of syndromes with many features in common in terms of clinical presentation, difficulty in assessment, timing of operative intervention, and operative management. Free wall rupture, which can be simulated by hemopericardium without rupture, is not always rapidly fatal. Successful intervention was achieved in six of the 13 cases in the free wall group. Ventricular septal defect occurs less frequently than free wall rupture, is more easily diagnosed, and less frequently requires urgent medical intervention. In 12 of the 14 cases of acute rupture, stabilization of the patient by conservative measures could not be achieved and operation was undertaken within 1 week of infarction. There were seven survivors, in four of whom the defect reopened, with successful reoperation in three. In the remaining 15 cases, stabilization by conservative measures was achieved and operation was delayed until at least 2 weeks after infarction. There were 14 survivors and only one instance of reopening of the defect.

Infected ventricular septal defect.

This paper reports a case of recurrent septic pulmonary emboli resulting from bacterial endocarditis on a ventricular septal defect. This was managed by the removal of vegetations, resection of the septal leaflet of the tricuspid valve, closure of the ventricular septal defect, and pulmonary embolectomy. The literature regarding the incidence and mortality of bacterial endocarditis on ventricular septal defects, and the management of the infected tricuspid valve, is reviewed. The patient remains well two and a half years after surgery.

Cardiac valve replacement (1963-1979).

A 15-year experience (from 1963-1978) in cardiac valve replacements with mechanical prosthetic valves (caged ball or tilting disc types) and with bioprostheses (porcine xenografts) is reported. The actuarial survival rates for patients who received the caged ball type prostheses (Starr-Edwards) were 42% and 36% respectively for mitral valve-replacements at 12 and 14 years. The actuarial survival rate for patients who received the tilting disc type prostheses (Björk-Shiley type and later the Lillehei-Kaster type) was 74% at six to seven years. The actuarial survival rate for patients who had aortic valve replacement with a caged ball valve was 43% at 14 years, and for those who had a tilting disc valve it was 80% at six to seven years. Multiple valve replacements were carried out with combinations of prostheses. The actuarial survival rate for patients was 65% for triple valves, and 57% for double valves at 13 years. Bioprostheses are now our first choice as cardiac valve replacements. In 121 implants performed since 1977, there have been two operative deaths, but no late deaths. Bioprostheses, although less thrombogenic than mechanical valve prostheses, are less durable and some risk of thromboembolism remains.