Problem-solving in clinical practice: Persisting respiratory distress in a premature infant.

The deterioration of a previously stable preterm infant is a common scenario on the neonatal unit. The the most common bacterial causes of deterioration are nosocomial infections, such as coagulase-negative Staphylococcus and Staphylococcus aureus Non-infective conditions such as pulmonary haemorrhage, anaemia of prematurity and necrotising enterocolitis may also cause preterm infants to deteriorate. This case chronicles the unusual diagnostic journey of an infant born at 27+1 weeks who deteriorated at 26 days of life and did not respond to antimicrobial therapy as anticipated.

An unusual pathogen in ambulatory care: two cases of Scedosporium soft tissue infections presenting as "unresponsive cellulitis".

Soft tissue infections with Scedosporium spp. are an uncommon but serious and emerging cause of infection in immunocompromised patients. Acute Medical Units (AMUs) in the UK are increasingly managing patients with cellulitis in an outpatient setting, therefore acute physicians should be aware of some of the more uncommon causes of soft tissue infection, particularly in patients not responding to initial antibiotic therapy. We present two cases of Scedosporium presenting to the AMU as cellulitis not responding to initial antibiotic therapy and outline the assessment and management of this important condition.

Whole-genome comparison of two Acinetobacter baumannii isolates from a single patient, where resistance developed during tigecycline therapy.

OBJECTIVES: The whole genomes of two Acinetobacter baumannii isolates recovered from a single patient were sequenced to gain insight into the nature and extent of genomic plasticity in this important nosocomial pathogen over the course of a short infection. The first, AB210, was recovered before tigecycline therapy and was susceptible to this agent; the second, AB211, was recovered after therapy and was resistant. METHODS: DNA from AB210 was sequenced by 454 GS FLX pyrosequencing according to the standard protocol for whole-genome shotgun sequencing, producing ∼250 bp fragment reads. AB211 was shotgun sequenced using the Illumina Genetic Analyzer to produce fragment reads of exactly 36 bp. Single nucleotide polymorphisms (SNPs) and large deletions detected in AB211 in relation to AB210 were confirmed by PCR and DNA sequencing. RESULTS: Automated gene prediction detected 3850 putative coding sequences (CDSs). Sequence analysis demonstrated the presence of plasmids pAB0057 and pACICU2 in both isolates. Eighteen putative SNPs were detected between the pre- and post-therapy isolates, AB210 and AB211. Three contigs in AB210 were not covered by reads in AB211, representing three deletions of ∼15, 44 and 17 kb. CONCLUSIONS: This study demonstrates that significant differences were detectable between two bacterial isolates recovered 1 week apart from the same patient, and reveals the potential of whole-genome sequencing as a tool for elucidating the processes responsible for changes in antibiotic susceptibility profiles.

AdeABC-mediated efflux and tigecycline MICs for epidemic clones of Acinetobacter baumannii.

OBJECTIVES: Tigecycline non-susceptibility in individual Acinetobacter baumannii isolates has been associated with up-regulation of the resistance-nodulation-division (RND)-type efflux system, AdeABC. We sought to relate variation in the expression of this system to differences in modal tigecycline MIC among prevalent A. baumannii clones. The role of AdeABC in the emergence of tigecycline resistance during therapy was also investigated for two representatives of the prevalent UK lineage, OXA-23 clone 1. METHODS: Clonal type was defined by PFGE and expression of adeABC by real-time RT-PCR. Laboratory mutants were selected in vitro by exposing a susceptible clinical isolate to increasing tigecycline concentrations. The adeB gene was inactivated by the directed integration of a suicide plasmid containing an internal fragment of the target gene. RESULTS: Higher modal tigecycline MICs for particular clones correlated with elevated expression of adeABC. Expression of this operon was also increased in the two post-therapy, tigecycline-resistant clinical isolates and in a laboratory mutant as compared with their pre-exposure, tigecycline-susceptible counterparts. Interruption of adeB in a tigecycline-resistant clinical isolate restored full susceptibility to tigecycline. CONCLUSIONS: Differences in expression of adeABC contribute to both inter- and intra-clone variation in tigecycline MICs. Tigecycline resistance can arise during therapy, mediated by up-regulation of AdeABC.

Early (2008-2010) hospital outbreak of Klebsiella pneumoniae producing OXA-48 carbapenemase in the UK.

OXA-48 ß-lactamase is one of the several emerging carbapenemases. Pre-2007 reports were almost exclusively from Turkey, but subsequently its distribution has expanded. We report an early and prolonged outbreak in the UK of Klebsiella pneumoniae producing OXA-48 carbapenemase affecting a predominantly renal cohort in a West London hospital. Carbapenemase production was detected by the modified Hodge test, with confirmation by PCR for bla(OXA-48). Isolates were typed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Risk factors for acquisition were determined. Between January 2008 and April 2010, 20 K. pneumoniae isolates with reduced susceptibility to carbapenems were identified from 13 patients, comprising 12 renal cases and 1 oncology patient; 8 were outpatients and 5 were inpatients; 7 were deemed to be colonised and 6 infected, including 2 with bacteraemia, 1 of whom died. Hodge tests were positive for all isolates and all had bla(OXA-48). PFGE showed strain similarity in isolates from nine patients, whereas four patients' isolates were distinct, representing three further PFGE profiles and suggesting horizontal spread of bla(OXA-48). Most patients had received antibiotics in the preceding 3 months and all had healthcare contact, but none had recent travel to areas with endemic OXA-48 Enterobacteriaceae. The renal cohort was screened and a prevalence rate of 0.17% was found. Interventions that collectively brought the outbreak under control included strict infection control precautions, screening, improved laboratory detection protocols and antibiotic stewardship rounds.