Background: Central venous lines (CVL) play a major role in the management of cancer in all age groups. CVL’s easily form biofilms, creating an excellent environment for bacterial growth. Eradication of CVC related blood stream infection continues to be one of the goals in management of cancer patients. The taurine amino-acid derivative, taurolidine, has broad antibacterial activity against both gram positive and negative organisms, possibly facilitated by bacterial cell wall disruption thus neutralizing endotoxin and exotoxin, and antiadherence properties. Previous small trials have shown decreased blood stream infections when taurolidine is used as a CVL lock (Taurolock) .
Method: This single centre open label RCT compared Taurolock versus standard heparin lock (250 IE heparin in 0.9% saline) in CVL’s with otherwise identical standard of insertion and care. Study period was from April 2008 till August 2012. Out Of 141 CVL’s eligible, 130 CVL’s from 113 patients participated in the trial after exclusion, with equal numbers in both arms. Most of the participants receiving Taurolock experienced a transient bad oral taste as a side effect and hence one patient withdrew from the trial. End points of the trial were: catheter related blood stream infection (CRBSI), time to first CRBSI, removal of CVL, death of the patient with CVL, transfer of the patient to other specialty where adherence to the trial protocol was in doubt or reaching end of the trial period. The inherent observer bias within the open label design was offset by the laboratory end points.
Interesting findings: Rate of total blood stream infection in Taurolocked CVL was 1.2 per 1,000 CVL days while it was 2.5 per 1,000 CVL days in heparin locked CVL`s. Incidence rate ratio (IRR)= 0.49 and P value = 0.004. The rate of CRBSI in Taurolock group was 0.4 per 1,000 CVL days compared to 1.4 per 1,000 CVL days. CRBSI with coagulase negative staphylococci decreased by 66% in Taurolock group. Exit site infections however were no different in both groups (0.3 Taurolock v 0.1 standard). CVL infection was indentified as the major reason for premature line removal in standard Heparin lock when compared to CVL locked with Taurolock. No line with Taurolock was removed due to occlusion.
Take home messages:
1. Taurolock is independently protective against CVL related BSI in children with cancer. 2. Taurolock was well tolerated and did not appear to compromise CVL patency in this small series – however larger numbers may be required to ensure this.
3. Taurolock can be considered as CVL locks for children with long term CVL’s which could reduce the associated infection related complications
4. Taurolock is however not a substitute for exemplary CVL care, but rather an adjunct.
Submitted by: Dr Arun Bojarajan (Paediatric ID registrar) and Dr Julia Clark, 16 May 2013.
(Katsuta T, Shoji K, Watanabe Y, Saitoh A.
Background and methods: Gram negative resistance is on the rise, and paediatric ID teams are increasingly being asked to assist with the management of children infected with ESBL producing Enterobacteriaceae. Therapeutic options are limited, and carbapenems are usually indicated for serious infections. Principles of antimicrobial stewardship would favour use of narrower spectrum antibiotics if appropriate, in order to reserve carbapenems where possible. Carbapenem therapy can also be problematic for the treatment of children with pyelonephritis who may be well enough to be managed at home.
This study retrospectively examined 54 children treated for ESBL positive pyelonephritis (defined as fever, pyuria and positive culture on catheter or clean catch samples), treated in a large tertiary children’s hospital in Tokyo between April 2009 and December 2010. Antibiotic choices were at the discretion of individual physicians, without any control over these decisions. No control group was included in the study. Treatment outcomes were resolution of fever, infection relapse within 4 weeks of completion of treatment, and cure (defined as absence of symptoms and no recurrence).
Main findings: 32/54 (59%) were treated empirically with an agent to which the organism was not susceptible. There was no significant difference in the length of fever between these and the ones who were initially treated with susceptible antibiotics (2.2 vs 2.0 days respectively; p=0.62). 30/32 were switched to effective antibiotics, after an average of 4.4 days. Definitive antibiotics were chosen based on susceptibility testing. 21 were given intravenous cefmetazole (2nd gen cephalosporin), and a handful were given pip/taz (n=3), gent (n=3), cipro (n=2) or mero (n=2). Oral agents were used in 28/54 (52%): cotrimoxazole (n=16), fosfomycin (n=7) and quinolones (n=5). Mean treatment duration was 13.7 days (range 7-24 days). All patients were cured of infection and no relapses were documented within 4 weeks of completion of therapy (although it is unclear how hard they looked).
Take-home messages: Non-carbapenem antibiotics, such as cephamycins (and possibly beta-lactam/beta-lactamase combinations) may have a role in the treatment of non-bacteraemic ESBL pyelonephritis, although the retrospective, observational nature of this study does not really provide robust evidence for such an approach. Prospective, randomised studies comparing carbapenem head-to-head against alternatives would be useful. Whilst the use of an alternative intravenous agent would have the advantage of ‘sparing’ carbapenems, finding a safe and effective oral option is a more pressing problem for individual children with pyelonephritis. Resistance to cotrimoxazole and quinolones is increasing, and fosfomycin use is limited by availability and a lack of paediatric data. This study describes treatment success for a small cohort of patients treated with fosfomycin, but further research into its use in paediatric pyelonephritis would be very valuable.
Submitted by Josh Francis, 9 April 2013
Two studies describing the herd effects of paediatric vaccines (both submitted by Tony Walls 15 March 2013)
Impact of the 7-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in infants younger than 90 days in England and Wales
(Ladhani et al. Clin Infect Dis. 2013 Mar;56(5):633-40)
Streptococcus pneumonia is an uncommon but well-recognised cause of invasive bacterial infection in young infants. The UK has had active surveillance for invasive pneumococcal disease (IPD) since 1998 through the Health Protection Agency. This study looked at trends in IPD in infants <90 days of age before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in September 2006. Prior to PCV7 introduction the incidence of IPD in infants <90 days of age was 13/100,000 live births (95%CI 12.0-14.0) with serotypes contained in PCV7 accounting for 44% of isolates. The highest rates of disease occurred in infants in the first week of life, and there was an overall case fatality ratio of 7%.
Following the introduction of PCV7 there was an 83% reduction in IPD due to vaccine serotypes. Most of these infants would have been too young to receive PCV vaccine and the authors suggest that this herd effect is due to a reduction in household transmission from vaccinated siblings. However the overall reduction of IPD in this group was small with an increase in non-vaccine serotypes causing disease.
(Anderson et al, Clin Infect Dis. 2013 Mar;56(6):755-60)
Routine use of rotavirus vaccine has been shown to provide indirect protection of unvaccinated children in both Australia and the USA. However it is not clear if this effect extends to adults. This study tested stored stool samples from adults that had been initially processed for routine bacterial stool cultures. This was used as a marker for significant diarrhoeal illness in this population. Inpatients and outpatients were included and the study compared results from 2006-7 (pre-vaccination era) and 2008-10 (post vaccination). They found a 48.4% decline in rotavirus detection from stools with an absolute reduction of 2.11% (p=0.0007). There was no associated decline in rotavirus-associated hospitalisations.
It is hard to know if these findings reflect a true reduction in adult rotavirus disease in the community. This was a single centre lab-based study, and a high proportion of patients who tested positive for rotavirus were immunocompromised. In addition the pre-vaccine era was quite short and included just one rotavirus season. However, it makes sense that rotavirus vaccination may reduce disease in adults who care for young children. The authors comment that even a small absolute reduction in adult rotavirus disease could lead to enormous cost savings in the USA. The potential effects on adults were never factored in to cost-effectiveness calculations made prior to rotavirus vaccine introduction.
Antibiotic exposure and IBD development among children: a population-based cohort study
(Kronman MP, Zaoutis TE, Haynes K, Feng R, Coffin SE. Pediatrics 2012;130:2011-3886.)
Background: This is a well designed, retrospective, population based cohort study that investigated the association between exposure to antianaerobic antibiotics in childhood (£ 17 years) with development of inflammatory bowel disease (IBD). Electronic records of > 9 million patients (5.7% of all UK (out)patient visits) from a network of 464 UK ambulatory practices (The Health Improvement Network, THIN, 1994-2009) were captured. Patients were classified as “ever” (64%) or “never” having had antibiotic exposures to antianaerobic antibiotics (penicillin, amoxicillin, ampicillin, and penicillin/ß-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin), by link to written prescriptions.* Primary outcome was IBD development (by validated definiton). Secondary outcome was by IBD according to classes of antibiotics. Patients were excluded if they recieved antibiotics during the “latency period” (study-defined time betwen onset of IBD symptoms and formal diagnosis) to address misclassification bias. Multivariate analysis included known co-mordities for IBD e.g. family history, CGD, primary sclerosing cholangitis. *Note (PP): the study assumes a “prescription” equates to actual consumption of antibitoics
Main findings: A total of 1, 072,426 children were included in analysis; 748 (0.07%) developed IBD. IBD incidence rates were 0.83 and 1.52 per 10,000 person-years in unexposed and exposed children, for an 84% relative risk increase. In multivariate analysis: the highest association was with co-morbidities. However, there was an independent, significant association with age of exposure to antibiotics, with a cumulative dose-response effect seen. Exposure before 1 year of age was associated with a 5.5 fold increased IBD risk [95% confidence interval, 1.66 - 18.28), decreasing to 2.62 [95% confidence interval, 2 - 18.28] at 5 years and to 1.57 [95% confidence interval, 1.66 - 18.28] by 15 years. Each anti-anaerobic course increased the risk for IBD by 6%. The effect was greatest for penicillins, broad spectrum penicillins, cephalosporins, metronidazole and flourquinolones. Antibiotics were prescribed for GIT reasons in only 1.6% and in 38.9%** no specific infectious diagnosis was found. [** Note: PP: implying that in nearly 40% of cases, antibiotics may have not been needed - commensurate with current literature where ~50% antibiotics use is inappropriate]. Results for patients by Crohn’s disease and ulcerative colitis were similar.
The results mean that for every 14 300 prescriptions for antibiotics with anaerobic cover, 1 child will develop IBD (UK) or an additional 1700 cases of IBD in the USA yearly.
Take home message: As infectious diseases physicians, we champion judicious antibiotic use. It is noteworthy when we can cite evidence that early antibiotic use is associated with a long term adverse outcome.This paper provides further fodder against the (repeated), inappropriate use of antibiotics, particularly in the young child. So, the message is not new: “If one uses antibiotics, think first if it is really needed, especially in the young child where the increase in IBD risk is 5 x above baseline, and higher with repeated courses”
Of note, the basis of this predisposition to IBD may lie with the diruption of normal healthy flora in early life, a subject that is the focus of many recent publications. Submitted by: Pam Palasanthiran, 15 February, 2013