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Twelve laboratories in different parts of Britain each supplied approximately 80 consecutive urinary bacterial isolates from community patients. All strains were identified by a central laboratory, where sensitivity to a variety of orally administered antimicrobials was determined by microtitre broth dilution. 65.1% of isolates were Escherichia coli, 23.4% 'coliforms' other than E. coli, 4.6% Proteus and Morganella spp., 1.8% Pseudomonas spp., 2.4% enterococci, 0.7% group B streptococci, 1.5% coagulase-negative staphylococci and 0.5% Staphylococcus aureus. Using previously published breakpoint sensitivity values, 98.9% of all isolates were found to be sensitive to norfloxacin and to ciprofloxacin, 95.7% to co-amoxiclav, 86.8% to nitrofurantoin, 77.4% to cephalexin, 75.6% to trimethoprim, 75.0% to cephradine and 51.7% to amoxycillin. There were some differences in sensitivities between centres, particularly those of the cephalosporins. Using standard breakpoints, submitting laboratories were found to overestimate sensitivity to nitrofurantoin and to underestimate sensitivity to the quinolones and to co-amoxiclav; there was considerable overestimation of sensitivity to cephalosporins. [ABSTRACT FROM AUTHOR]

Rationale: Longitudinal epidemiological and clinical data are needed to improve the management of patients with bronchiectasis developing nontuberculous mycobacterial (NTM) pulmonary disease., Objectives: To describe the epidemiology, patient management, and treatment outcomes of NTM infections in patients with bronchiectasis enrolled in the United States Bronchiectasis and NTM Research Registry (US BRR)., Methods: This was a retrospective cohort study of patients with bronchiectasis and NTM infections enrolled with follow-up in the US BRR in 2008-2019. The study included patients with ≥1 positive NTM respiratory culture in the 24-month baseline period (baseline NTM cohort) and/or during the annual follow-up visits (incident NTM cohort). Incidence, prevalence, baseline patient characteristics, treatment exposure, treatment outcomes, and respiratory clinical outcomes were described in the baseline NTM cohort, incident NTM cohort, and both cohorts combined (prevalent NTM cohort)., Results: Between 2008 and 2019, 37.9% (1457/3840) of patients with bronchiectasis in the US BRR met the inclusion criteria for this study and were reported to have Mycobacterium avium complex (MAC) and/or Mycobacterium abscessus complex (MABSC) infections. MAC prevalence increased steadily in the US BRR during 2009-2019; incidence was relatively stable, except for a peak in 2011 followed by a slow decrease. MABSC and mixed MAC/MABSC infections were rare. Most patients with bronchiectasis and NTM infections in the registry were female, White, and aged >65 years. The antibiotics administered most commonly reflected current guidelines. In the prevalent cohort, 44.9% of MAC infections and 37.1% of MABSC infections remained untreated during follow-up, and MAC treatment was initiated with delay (>90 days after positive NTM respiratory culture) twice as frequently as promptly (≤90 days after positive NTM respiratory culture) (68.6% vs 31.4%, respectively). The median time from diagnosis to treatment was shorter for MABSC versus MAC infections (194.0 days [interquartile range (IQR) 8.0, 380.0] vs 296.0 days [IQR 35.0, 705.0], respectively). Among patients with MAC infections who completed treatment, 27.6% were classified as cured and 29.6% as treatment failure during the annual follow-up visit window. For MABSC, these proportions were 25.0% and 28.0%, respectively., Conclusions: A considerable proportion of MAC and MABSC infections were untreated or treated after initial delay/observation. MABSC infections were more likely to be treated and start treatment sooner than MAC infections. Further longitudinal studies are warranted to evaluate the monitor-with-delay approach and inform clinical guidelines., Competing Interests: Declaration of competing interest MD, HS, IG, ST, SS: employees of GSK and GSK shareholders at the time of this study; all GSK employees were involved in the study design, decision to publish, data analysis and interpretation, and preparation of the manuscript. ST: scientific liaison officer of The Union; deputy editor of the International Journal of Tuberculosis and Lung Disease. CS: speaker fees from Insmed. DM: consulting fees from AstraZeneca and COPD Foundation; honoraria from Medscape; payment for expert testimony from Schlesinger Law Firm; stock or stock options with GSK and Johnson and Johnson. MM: advisory board, grants, and consulting fees from Insmed. NL: grants for educational projects and conference travel fees from Insmed. PMS: grants as primary investigator for clinical trials from AN2 Therapeutics, Boehringer Ingelheim, Electromed, Hillrom, Insmed, Parateck, RedHill Biopharma, and Revovion; honorarium for steering committee from Insmed; speaker fees for Arikayce from Insmed. KW: grants and/or consulting fees from AN2, Insmed, Paratek, Renovion, RedHill Biopharma, and Vast; advisory board fees from RedHill Biopharma., (Copyright © 2023. Published by Elsevier Ltd.)

Community-acquired respiratory infections are usually treated empirically by the primary care physician. Increasing antibiotic resistance, for example, in pneumococci, prompted a UK survey of antibiotic susceptibility of three major lower respiratory tract pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Each of 27 centres was asked to collect up to 100 isolates of the three species and submit them for confirmation of identity and for susceptibility testing to a central laboratory. In addition, general practitioners were asked for demographic details on the patient, their treatment and the clinical outcome. Of 1689 viable pathogens collected, there were 1078 (64%) strains of H. influenzae, 258 (15%) of M. catarrhalis and 353 (21%) of S. pneumoniae. Production of beta-lactamase was detected in 163 (15%) of 1078 isolates of H. influenzae and in 243 (94%) isolates of M. catarrhalis. For S. pneumoniae, moderate resistance to penicillin (MIC 0.12-1 mg/l) was found in 12 (3.4%) isolates and high level resistance (MIC > or = 2 mg/l) in 13 (3.7%) isolates. The most common individual treatments were amoxycillin, amoxycillin/clavulanate (amoxyclav) , and erythromycin. Complete or partial clinical resolution was achieved in 88% of 809 patients infected with H. influenzae, 83% of 197 infected with M. catarrhalis and 90% of 255 infected with S. pneumoniae.

Despite potential nephrotoxicity and ototoxicity, aminoglycosides are widely used in the treatment of severe sepsis but monitoring of serum levels is necessary. The use and assay of aminoglycosides, together with microbiologists' and pharmacists' advice on dosage and potential toxicity were examined in a teaching hospital group during an eight week period. A total of 480 courses of aminoglycoside was recorded in 440 hospital in-patients and of these, 306 (64%) were for prophylaxis. For 79 (45%) of 174 therapeutic courses, bacteriological results were available at the start and the choice of antibiotic was appropriate in 69 cases. Serum aminoglycoside assays were performed in 86% (149/174) of therapeutic courses. Correct assay request forms were used in 79% of 473 assay requests, and the clinical diagnosis was given on 73% of forms. In so-called peak samples with a documented time of collection, this ranged from 5 min to over 9 h post dose. Potentially toxic concentrations were present in 56 (12%) serum samples from 50 courses, in ten of which there was a serum creatinine rise of > 40 microM. However, there were confounding factors in five cases. Probable nephrotoxicity was rare, although assays were not performed in 14% of therapeutic courses. There were no symptomatic cases of ototoxicity but audiometry and vestibular studies were not performed. Closer liaison between the microbiologists, pharmacists and clinical staff is essential to improve clinical practice. Computer notification of inadequately monitored courses would be helpful. The routine therapeutic use of aminoglycosides needs to be reviewed in the light of the rising costs of assay litigation and the increasing number of alternative antibiotics available.

An outbreak of diarrhoea occurred in an acute geriatric ward of a hospital (A). It affected six patients initially and was found to be due to a single strain of Clostridium difficile. There was little evidence for asymptomatic carriage of this strain or others in the hospital patients. The following three months saw an increase in the number of symptomatic cases of C. difficile disease in two peripheral hospitals, B and C. Patients had been moved from the outbreak ward to these hospitals. Of 18 cases in hospital B all 15 isolates saved for typing were of the 'outbreak' strain. Of three cases occurring in hospital C, only one was the 'outbreak' strain (a relapsed patient who was part of the original episode). There were seven further cases in geriatric and medical wards of hospital A. All six typed isolates were also the outbreak strain. By chance, four isolates from hospital A and four from hospital B pre-dating the outbreak were also available for typing and seven of these were found to be identical to the outbreak strain. This suggests that one strain of C. difficile was endemic in geriatric and medical facilities on two sites and was responsible for nosocomial diarrhoea over at least one year. The problems of optimal management and infection control in this situation are discussed.

The entire coding region of the polymerase-associated (P) protein gene of canine distemper virus has been sequenced. A single cDNA clone which represents 98% of the mRNA encoding this protein was used to determine the nucleotide sequence. The sequence predicts a major protein of 507 amino acids and a molecular weight of 54 936. There is also a second, overlapping, open reading frame with a start signal 21 bases downstream of the first AUG which could code for a protein of 174 amino acids with a predicted molecular weight of 20 292. This arrangement of the genome for the P protein of canine distemper virus is exactly analogous to that published recently for the P gene of measles virus (Bellini, W.J. et al., 1985, J. Virol. 53, 908-919). When the sequences are aligned at the first AUG, considerable homology is seen at both the nucleotide and protein sequence level.