About the Author(s)


Nina von Knorring Email symbol
Division of Clinical Microbiology and Infectious Diseases, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa

Microbiology Laboratory, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, South Africa

Trusha Nana symbol
Division of Clinical Microbiology and Infectious Diseases, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa

Microbiology Laboratory, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, South Africa

Vindana Chibabhai symbol
Division of Clinical Microbiology and Infectious Diseases, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa

Microbiology Laboratory, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, South Africa

Citation


Von Knorring N, Nana T, Chibabhai V. Cumulative antimicrobial susceptibility data for a tertiary-level paediatric oncology unit in Johannesburg, South Africa. S. Afr. j. oncol. 2019;3(0), a65. https://doi.org/10.4102/sajo.v3i0.65

Original Research

Cumulative antimicrobial susceptibility data for a tertiary-level paediatric oncology unit in Johannesburg, South Africa

Nina von Knorring, Trusha Nana, Vindana Chibabhai

Received: 06 Dec. 2018; Accepted: 24 Jan. 2019; Published: 27 May 2019

Copyright: © 2019. The Author(s). Licensee: AOSIS.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: There is global concern regarding the spread of antimicrobial resistance in bacteria and fungi. Oncology patients are at particular risk of infections with multidrug resistant organisms. These patients require urgent initiation of empiric antimicrobial therapy when presenting with neutropenic fever. Currently, piperacillin-tazobactam and amikacin with or without vancomycin is the treatment of choice in the unit.

Aim: The purpose of this study was to develop a cumulative antibiogram for the paediatric oncology unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) to guide empiric treatment recommendations for patients presenting with suspected bacterial or fungal infection.

Setting: Tertiary-level paediatric oncology unit.

Methods: A retrospective observational analysis was performed of bacterial and fungal antimicrobial susceptibility data extracted from the microbiology laboratory information system for clinical specimens submitted from the paediatric oncology unit at CMJAH. Data was analysed for the period January 2015 to May 2018. In addition, analysis and comparison of two 17-month time periods was performed in order to elicit any changes over time.

Results: Klebsiella pneumoniae and Escherichia coli were the most common gram-negative organisms isolated. Twenty-one percent of Enterobacteriaceae showed resistance to third generation cephalosporins and 9% to carbapenems. Rates of carbapenem-resistant isolates decreased significantly over time. Adding amikacin to piperacillin-tazobactam significantly increased bacterial coverage. Coagulase-negative staphylococci and Candida parapsilosis were the most common gram-positive and fungal isolates recovered during the study.

Conclusion: The results support the continued use of piperacillin-tazobactam and amikacin for paediatric oncology patients presenting with neutropenic fever in this unit. Antibiograms are an important component of antimicrobial stewardship in conjunction with efficient infection prevention and control measures.

Keywords: governance; big data; controls; control framework; antibiogram; paediatric oncology; antimicrobial resistance; antimicrobial stewardship; infection prevention and control.

Introduction

The World Economic Forum has declared antimicrobial resistance the next major global challenge.1 It is a significant cause of morbidity and mortality, especially in hospitalised patients.2,3 Oncology patients on chemotherapy are at particular risk of bacterial and fungal infections and require urgent initiation of empiric antibiotics when presenting with neutropenic fever. They are also likely to harbour drug resistant organisms, and delayed initiation of appropriate therapy is associated with poor outcomes.4,5,6

Numerous studies in paediatric oncology units have raised concerns about the increase in resistant pathogens.7,8,9,10 The National Institute for Communicable Diseases (NICD) carries out surveillance in South Africa and collates resistance data from both public- and private-sector laboratories, which it publishes annually. The data shows that resistance in general is increasing in certain gram-negative bacteria and yeasts. Gram-negative organisms are increasingly producing extended spectrum β-lactamase (ESBL) and carbapenemase enzymes, which hydrolyse broad-spectrum antibiotics. The NICD surveillance of bloodstream infections Group of Enteric, Respiratory and Meningeal Diseases Surveillance in South Africa (GERMS-SA) showed an increase in Klebsiella pneumoniae isolates with ESBL phenotype from 62% to 75% between 2010 and 2012. Reporting of carbapenem-resistant Enterobacteriaceae (CRE) isolates was added in 2015, and case numbers increased significantly over the subsequent years.11 Resistance to commonly used antifungal drugs, such as azoles, is developing in yeasts, and there is a shift towards a higher prevalence of species that are inherently resistant to these agents, such as Candida glabrata and C. auris.12,13 Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), which are known to be particularly difficult to treat in neutropenic patients, are being detected in 24% and 5% of the respective species according to GERMS-SA reports.11

Antimicrobial stewardship is a crucial intervention to guide the appropriate use of antibiotics, and stewardship programmes are recommended for all health care facilities.14,15 Ideally these programmes should be in place where patients with cancer are treated to guide and monitor antimicrobial treatment practices.16,17,18 A recent meta-analysis by Baur et al. demonstrated that antimicrobial stewardship can indeed significantly reduce infection and colonisation with multidrug resistant organisms especially in the haemato-oncology setting.19 It has also been associated with lower mortality in adult oncology patients with neutropenia.20 In addition, stewardship can have a positive impact on the rate of adverse drug reactions and overall health care expenditure.21

Cumulative antibiograms are an integral aspect of antimicrobial stewardship programmes.14 They depict the spectrum of microorganisms and susceptibility profiles in a specific location or hospital unit over time and are used to direct the choice of empiric treatment of suspected bacterial or fungal infection prior to the availability of results from cultured specimens.21,22 In addition to optimising patient management, antibiograms inform infection prevention and control practices and assist with monitoring strategies of these interventions. The Clinical and Laboratory Standards Institute (CLSI) has published guidelines in order to standardise the methodology used for antibiogram development and reporting.23,24

The 24-bed paediatric oncology ward and outpatient department at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) manages medical and surgical patients with haemato-lymphatic malignancies, solid tumours as well as benign haematological disorders. Prior to this analysis, patients with suspected neutropenic fever were treated empirically with piperacillin-tazobactam and amikacin with the addition of vancomycin for those with intravenous catheters.

The aim of the study was to compile an antibiogram for the paediatric oncology unit at CMJAH with the intention of guiding empiric treatment recommendations for patients presenting with suspected bacterial or fungal infection. Results may further be used to direct infection prevention and control measures in this unit.

Methods

A retrospective observational analysis was performed of bacterial and fungal identification and susceptibility data generated for paediatric oncology patients at the National Health Laboratory Service (NHLS) Microbiology Laboratory at CMJAH between January 2015 and May 2018. Isolates cultured from blood, cerebrospinal fluid, urine, the respiratory tract, tissue, pus, catheter tips and swabs were included in the analysis. As per the laboratory’s standard operating procedures, the majority of isolates were processed using the automated identification and susceptibility testing system Vitek®2 (bioMérieux, Marcy l’Étoile, France). A smaller proportion of isolates were identified using manual biochemical and conventional Kirby-Bauer disk diffusion susceptibility testing methods (mainly urinary isolates).Enterobacteriaceae with reduced susceptibility to carbapenems were tested using a gradient diffusion susceptibility test (ETEST® bioMérieux) for accurate determination of the minimum inhibitory concentration (MIC). From 2017 organism identification was also performed using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS, Vitek® MS bioMérieux). Susceptibility results were only reported for antimicrobials routinely tested by the laboratory and used for clinical management and were interpreted according to CLSI guidelines for the relevant year.25,26

Data for paediatric oncology outpatients and ward patients at CMJAH was extracted from the laboratory interface system database TrakCare® (InterSystems, Cambridge, MA, USA) and sorted per organism to species level (for gram-positive bacteria, gram-negative bacteria and yeasts). In order to reduce selection bias, repeat patient isolates of the same species were removed according to the patient-based algorithm described in the CLSI guidelines.24 Therefore, only the first isolate of a specific organism per patient was included regardless of specimen type or site. In addition to the susceptibility to individual antimicrobials, analysis of the empiric combination of agents used in the unit was also performed to assess the effect on antimicrobial coverage. In order to obtain the highest possible number of isolates per species, data was collated and analysed for the period January 2015 to May 2018. To determine if a change in susceptibility rates occurred amongst the most prevalent pathogens, a second analysis was performed for two separate periods representing the start and end of the analysis period, January 2015 to May 2016 and January 2017 to May 2018. Analysis of the gram-negative organisms was performed both at species level and combined as Enterobacteriaceae and non-fermenters because of the relatively lower isolate numbers available for analysis in the chosen periods. Data were presented as proportions and percentages with confidence intervals for individual antimicrobials. Fisher’s exact test (GraphPad Software, San Diego, USA) was used to establish any statistically significant differences in susceptibility rates between the two 17-month periods. The p-values were reported as two-tailed, with values < 0.05 considered to be statistically significant.

Isolates with any carbapenem MIC above the susceptible range were referred for molecular confirmation of carbapenemase genes. For the purpose of this analysis a CRE describes isolates that had non-susceptible carbapenem MICs on gradient diffusion test with or without molecular confirmation. Pseudomonas and Acinetobacter species were reported as extensively drug resistant if only susceptible to two or fewer classes of antibiotics. Colistin susceptibility was not analysed, as the majority of isolates were not tested by broth microdilution according to current CLSI recommendations. Data on tobramycin was also excluded as it was only available for urinary isolates processed by the Kirby-Bauer disk diffusion method.

Ethical consideration

The study was approved by the Human Research Ethics Committee, University of the Witwatersrand (protocol no. M180991).

Results

A total of 263 paediatric patients seen in the oncology department at CMJAH between January 2015 and May 2018 were included in the analysis, generating 438 initial episodes of cultured isolates after removal of duplicate specimens (n = 215) and miscellaneous species (n = 17).

Gram-negative bacteria

The majority of organisms were gram-negative bacilli (n = 214, 49%; Figure 1), mainly cultured from blood and urine specimens (Table 1). Klebsiella pneumoniae and Escherichia coli in equal numbers were the main species in this group (Table 2). Of the Enterobacteriaceae, 35 (21%, 95% confidence interval [CI] 15–28) showed resistance to one or both third generation cephalosporins (ceftriaxone/ceftazidime). All gram-negative organisms combined appear highly susceptible to the carbapenems, imipenem and meropenem (93% and 92%, respectively). Fifteen Enterobacteriaceae isolates displayed resistance to the carbapenems (9%, 95% CI 5–14; ertapenem, meropenem or imipenem).

FIGURE 1: Gram-negative antibiogram.

TABLE 1: Organism distribution and site.
TABLE 2: Bacterial and fungal identification and frequency.

Extensive drug resistance was found in 15% (n = 7, 95% CI 7–28) of non-fermenters analysed. Pseudomonas species were the most common non-fermenter organisms and showed susceptibilities between 79% and 89% to antimicrobial agents tested. Susceptibility to the anti-pseudomonal carbapenems, meropenem and imipenem, was particularly high (89%; n = 28 and 27, respectively). Acinetobacter species represented the second largest group of non-fermenters; these demonstrated lower susceptibility rates to the standard antibiotics tested compared to Pseudomonas species (range 47% – 79%).

A comparison of the two analysis periods shows a significant increase in E. coli isolates mainly from urine specimens (20% to 36%, p = 0.02). The proportion of Enterobacteriaceae resistant to third generation cephalosporins remained unchanged (21% and 17%, p = 0.53). However, of note, the proportion with carbapenem resistance decreased significantly (18% and 4%, p = 0.008).

At species level there was a considerable increase in susceptibility of K. pneumoniae isolates to piperacillin-tazobactam and ciprofloxacin, though these were not statistically significant (42% vs. 70%, p = 0.08, and 54% vs. 91%, p = 0.06, respectively). Overall there was a non-significant increase in susceptibility of gram-negative organisms with regard to meropenem and imipenem between the two time periods (89% vs. 97%, p = 0.07).Ciprofloxacin susceptibility also increased from 79% to 87% across all gram-negative bacteria, but this was not statistically significant (p = 0.21).

Comparing piperacillin-tazobactam susceptibility alone versus piperacillin-tazobactam and amikacin in combination reveals a statistically significant increase in the proportion of susceptible isolates in favour of combination therapy (76% monotherapy vs. 89% for combination therapy, p = 0.0005; Table 3).

TABLE 3: Comparison of overall antibacterial coverage achieved by piperacillin-tazobactam alone versus piperacillin-tazobactam and amikacin. combined. Gram-negative organisms 2015–2018.
Gram-positive bacteria

Staphylococcus species represent the largest proportion of gram-positive organisms cultured (n = 134, 72%; Figure 2).The vast majority of these were identified as coagulase-negative staphylococci (CONS) from blood culture specimens; approximately one-third was susceptible to cloxacillin (n = 35, 35%). The proportion of CONS isolates considered clinically significant was not retrospectively established. Methicillin resistance was found in five (15%) S. aureus isolates. Enterococcus species accounted for the second largest group of gram-positive organisms (n = 29, 16%) and showed a non-significant trend towards increased vancomycin resistance between the two time periods, although overall numbers remained low (n = 1 and n = 7, p = 0.09). Seven of the nine vancomycin-resistant isolates cultured over the entire time period originated from sterile sites. In total 22 (12%) isolates belonging to the viridans streptococci were isolated from sterile sites.

FIGURE 2: Gram-positive antibiogram.

Yeasts

Only 39 yeast isolates (comprising 9% of all isolates; Figure 3) were identified during the study period. Candida parapsilosis accounted for the majority of specimens (n = 17, 44%); all but one of these isolates were susceptible to fluconazole. There were 11 (28%) Candida albicans isolates. The first and only isolate of multidrug resistant C. auris in the unit at the time of writing this manuscript was detected in January 2018.

FIGURE 3: Yeasts.

Discussion

The results of this cumulative antibiogram provide a basis for the rational selection of empiric antimicrobial therapy in the paediatric oncology ward at CMJAH. They confirm the broad coverage provided bypiperacillin-tazobactam and amikacin against the main initial bacterial pathogens cultured from these patients.

Compliance with CLSI guidance on antibiogram development as well as analysis of individual episodes according to the CLSI patient-based algorithm was undertaken to minimise selection bias and provide a basis for selection of empiric therapy for initial presentation with suspected bacterial or fungal infection. However, this method is likely to miss changes in resistance profiles within individual patients presenting with repeated episodes of infection caused by the same organism and the emergence of new patterns of resistance within the unit. To address this issue a comparison of isolates taken at the beginning and end of the observation period was performed. This allowed a cautious assessment of possible changes over time to be made. It remains critically important to take any previous culture results into consideration when making individual antimicrobial choices.24 Differentiating between community-acquired and nosocomial infections is often less clear in these high-risk patients because of their frequent exposure to health care facilities and antimicrobial therapy.

Differences in methodology limit comparison of our findings to previous research on infections and microbial susceptibility in paediatric oncology patients in South Africa.27,28,29 A study at the Chris Hani Baragwanath Hospital oncology unit situated in the same province reported on a large cohort of patients enrolled and followed up between 2009 and 2014.27 Their analysis of blood cultures taken during septic episodes showed overall lower susceptibility to commonly used antibiotics with larger proportions of ESBL producers in gram-negative isolates and MRSA and VRE in gram-positives. However, all patient samples were included rather than initial episodes, thus reflecting possible treatment-induced resistance. The large variation in susceptibility profiles between centres and sites is evident in an extensive literature review by Mikulska et al.30 and underlines the importance of acquiring local and current data. The results presented here should therefore not be extrapolated to other centres and require periodic updates.

The relatively high levels of susceptibility to antimicrobials observed in gram-negative organisms and the positive trend of decreasing resistance seen over time is encouraging. The carbapenem-free empiric treatment regimen employed by the oncology unit and effective infection control measures may have contributed to this outcome. Increasing numbers of CRE isolates detected between September 2015 and March 2016 led to the implementation of more rigorous hand hygiene measures and environmental cleaning, which may have had a positive influence on resistance rates. However, the antimicrobial resistance rates of Acinetobacter spp. seen in this antibiogram are of concern. These are in keeping with national results, which have now led to enhanced surveillance of Acinetobacter baumannii in South Africa.

Other aspects of antimicrobial stewardship with regard to the combination piperacillin-tazobactam and amikacin such as drug side-effects and cost have not been assessed here. The search for the optimal carbapenem-sparing regimen with sufficient activity against ESBL-producers and acceptable safety profile is ongoing.31 To date there is no consensus on the ideal empiric choice of antimicrobial treatment for this patient group.17 Local and patient-specific factors such as age, microbial profiles, drug side-effects, likely effect on selection of resistance and cost need to be considered. In these vulnerable patients it is important to balance the need for initial broad antimicrobial coverage against the possible increase in selection pressure and development of resistance. A study by Castagnola et al. on empiric therapy for patients with neutropenic fever suggests adding a second drug if resistance to the single agent is ≥ 10%, hence the addition of amikacin to piperacillin-tazobactam for patients in this unit is indicated.32 Unfortunately antibiotics with activity against multidrug resistant gram-negative organisms are scarce and are often associated with considerable collateral damage.33 This dilemma highlights the importance of using antibiograms in addition to patient treatment history to tailor empiric therapy. The antibiogram can also be employed in conjunction with rapid identification methods such as MALDI-TOF when choosing empiric antimicrobials based on organism identification while susceptibility results are still pending.

The decision to add vancomycin to the empiric regimen should be taken judiciously in order to avoid overuse and further selection of resistance in enterococcal isolates. Broad-spectrum antibiotics such as vancomycin alter the resident gut flora and favour overgrowth of bacteria with acquired or natural resistance. There is some evidence to support the use of chlorhexidine baths for patients colonised or infected with VRE.34 Gastrointestinal decolonisation strategies have unfortunately not been successful, and infection control measures are largely based on standard precautions, contact precautions, rectal screening and patient isolation.35,36 In cases where vancomycin is given, care should be taken to review the need to continue this once Gram stain and culture results are available. The decision to add vancomycin to the empiric treatment regimen in this unit will be based on the large number of CONS isolates and the perceived risk for an invasive CONS infection in the individual patient. These are often of uncertain clinical significance in these complex patients. The microbiology laboratory should assist in assessing the relevance of these and encourage appropriate culture techniques where possible. The relatively large proportion of viridians species seen in our study is also in keeping with the literature.30 Despite being commensals of the respiratory and gastrointestinal tract they are recognised opportunistic pathogens in this group of patients.

The shift in yeast isolates from C. albicans to non-albicans Candida species as seen in comparison to previous studies in the region is in keeping with countrywide epidemiology.11,27 Surprisingly the C. parapsilosis isolates found in our patients were almost exclusively susceptible to fluconazole in contrast to other hospital units where azole-resistant C. parapsilosis isolates predominate.37 However, this is unlikely to affect empiric antifungal treatment recommendations for the unit as fungicidal agents like the echinocandins or amphotericin B are indicated for initial therapy in neutropenic patients.38 Antifungal stewardship should remain a critical component of antimicrobial stewardship in these patients.

There are several limitations to this study. Despite collating and analysing a large data set, several organisms did not achieve the CLSI recommended target of 30 isolates per species. This was especially problematic for the analysis of the two separate data sets comparing 2015–2016 and 2017–2018. Therefore, these results should be interpreted with caution. These types of challenges are well recognised and discussed in the CLSI guidelines themselves, as well as in other publications.15,22,24 A further limiting factor was the retrospective nature of this analysis, which did not allow for confirmation of species identification or susceptibility results. Advances in microbial identification methods during the study period and subsequent changes to processing may have affected results. Moreover, inadvertent changes to collection practices of clinical samples over the years may have had an impact on the number and types of organisms isolated. This may explain the increase in urinary E.coli isolates observed here. The study population represents a heterogeneous group of patients in terms of diagnoses, and this study did not include analysis of demographic and clinical data. Neither the clinical significance of known skin and mucous membrane commensals nor the significance of samples taken from non-sterile sites could be established.

Going forward, it would be beneficial to include and interpret repeat patient isolates in a separate analysis, enabling more accurate assessment of the development of antimicrobial resistance and guidance on the management of health care associated infections. Further data analysis should also look at possible treatment recommendations for infectious syndromes and the development of a local protocol for the unit. Because antimicrobial in vitro susceptibility does not necessarily equate to in vivo activity, clinical outcome data would be of value to assess the efficacy of the empiric regimen.16 While continuous antimicrobial resistance monitoring takes place at CMJAH, this analysis of the bacterial spectrum and susceptibility is the first to be conducted specifically for the paediatric oncology unit, with further assessment planned at 12–18 month intervals.

In conclusion, the findings of this cumulative antibiogram support the continued use of piperacillin-tazobactam and amikacin as empiric regimen for paediatric oncology patients presenting with suspected bacterial infection at CMJAH. This is encouraging, since this combination is in keeping with recommendations made by various international guidelines.4,39 Cumulative antibiograms are a fundamental component of antimicrobial stewardship programmes guiding the appropriate selection of empiric therapeutic agents. This is of paramount importance for optimal patient outcomes and preservation of the activity of the limited antimicrobials currently available in an era of multidrug and extensive drug resistance.

Acknowledgements

The authors acknowledge Prof. J.E. Poole and Dr N. Beringer, Division of Paediatric Haematology and Oncology, CMJAH, for their support.

Competing interests

The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

Authors’ contributions

V.C. and T.N. conceptualised the study. N.v.K. collated and analysed the data. All authors read and approved the manuscript.

References

  1. World Economic Forum. Antibiotic resistance is the next great global challenge – We must act now. [homepage on the Internet]. 2016[cited 2018 Oct 18]. Available from: https://www.weforum.org/agenda/2016/09/antimicrobial-resistance-is-the-next-global-commons-issue/
  2. WHO. GLASS | Global antimicrobial resistance surveillance system (GLASS) report [homepage on the Internet]. WHO. 2018[cited 2018 Jul 12]. Available from: http://www.who.int/glass/resources/publications/early-implementation-report/en/
  3. Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: A global multifaceted phenomenon. Pathog Glob Health. 2015;109(7):309–318. https://doi.org/10.1179/2047773215Y.0000000030
  4. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2011;52(4):e56–e93. https://doi.org/10.1093/cid/cir073
  5. Simon A, Furtwängler R, Graf N, et al. Surveillance of bloodstream infections in pediatric cancer centers - what have we learned and how do we move on? GMS Hyg Infect Control. 2016;11:Doc11.
  6. Haeusler GM, Sung L, Ammann RA, Phillips B. Management of fever and neutropenia in paediatric cancer patients: Room for improvement? Antimicrob Agents. 2015;28(6):7. https://doi.org/10.1097/QCO.0000000000000208
  7. Bhat V, Gupta S, Kelkar R, et al. Bacteriological profile and antibiotic susceptibility patterns of clinical isolates in a tertiary care cancer center. Indian J Med PaediatrOncol. 2016;37(1):20–24. https://doi.org/10.4103/0971-5851.177010
  8. Radha Rani D, Sridevi Chaitanya B, Senthil Rajappa J, et al. Retrospective analysis of blood stream infections and antibiotic susceptibility pattern of gram negative bacteria in a tertiary care cancer hospital. Int J Med Res Health Sci. 2017;6(12):19–26.
  9. Taj M, Farzana T, Shah T, Maqsood S, Ahmed SS, Shamsi TS. Clinical and microbiological profile of pathogens in febrile neutropenia in hematological malignancies: A single center prospective analysis. J Oncol [serial online]. 2015 [cited 2018 Jul 12]. Available from: https://www.hindawi.com/journals/jo/2015/596504/
  10. Thacker N, Pereira N, Banavali SD, et al. Epidemiology of blood stream infections in pediatric patients at a Tertiary Care Cancer Centre. Indian J Cancer. 2014;51(4):438–441. https://doi.org/10.4103/0019-509X.175311
  11. GERMS-SA annual reports 2006-2017. [homepage on the Internet]. NICD. [cited 2018 Oct 19]. Available from: http://www.nicd.ac.za/index.php/publications/
  12. Chowdhary A, Sharma C, Meis JF. Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoSPathog. 2017;13(5):e1006290. https://doi.org/10.1371/journal.ppat.1006290
  13. Naicker SD, Magobo RE, Zulu TG, et al. Two echinocandin-resistant Candida glabrata FKS mutants from South Africa. Med Mycol Case Rep. 2016;11:24–26. https://doi.org/10.1016/j.mmcr.2016.03.004
  14. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016;62(10):e51–e77.
  15. Morency-Potvin P, Schwartz DN, Weinstein RA. Antimicrobial stewardship: How the microbiology laboratory can right the ship. ClinMicrobiol Rev. 2017;30(1):381–407.
  16. Gyssens IC, Kern WV, Livermore DM. The role of antibiotic stewardship in limiting antibacterial resistance among hematology patients. Haematologica. 2013;98(12):1821–1825. https://doi.org/10.3324/haematol.2013.091769
  17. Tverdek FP, Rolston KV, Chemaly RF. Antimicrobial stewardship in patients with cancer. Pharmacotherapy. 2012;32(8):722–734. https://doi.org/10.1002/j.1875-9114.2012.01162.x
  18. Newland JG, Banerjee R, Gerber JS, Hersh AL, Steinke L, Weissman SJ. Antimicrobial stewardship in pediatric care: Strategies and future directions. Pharmacother J Hum Pharmacol Drug Ther. 2012;32(8):735–743. https://doi.org/10.1002/j.1875-9114.2012.01155.x
  19. Baur D, Gladstone BP, Burkert F, et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: A systematic review and meta-analysis. Lancet Infect Dis. 2017;17(9):990–1001. https://doi.org/10.1016/S1473-3099(17)30325-0
  20. Rosa RG, Goldani LZ, Dos Santos RP. Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: A prospective cohort study. BMC Infect Dis. 2014;14:286. https://doi.org/10.1186/1471-2334-14-286
  21. Owens RC. Antimicrobial stewardship: Concepts and strategies in the 21st century. DiagnMicrobiol Infect Dis. 2008;61(1):110–128. https://doi.org/10.1016/j.diagmicrobio.2008.02.012
  22. Joshi S. Hospital antibiogram: A necessity. Indian J Med Microbiol. 2010 Dec;28(4):277–280. https://doi.org/10.4103/0255-0857.71802
  23. Hindler JF, Stelling J. Analysis and presentation of cumulative antibiograms: A new consensus guideline from the Clinical and Laboratory Standards Institute. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;44(6):867–873. https://doi.org/10.1086/511864
  24. Hindler JA et al. M39A4: Analysis and presentation of cumulative AST data [homepage on the Internet]. CLSI. 2014[cited 2018 Jul 12]. Available from: https://clsi.org/standards/products/microbiology/documents/m39/
  25. Weinstein MP et al. M100Ed28 | Performance Standards for Antimicrobial Susceptibility Testing, 28th Edition [homepage on the Internet]. Clinical & Laboratory Standards Institute. 2018 [cited 2018 Jul 12]. Available from: https://clsi.org/media/1930/m100ed28_sample.pdf
  26. Clinical & Laboratory Standards Institute. CLSI guidelines [homepage on the Internet]. Clinical & Laboratory Standards Institute. [cited 2018 Oct 19]. Available from: https://clsi.org/
  27. Naidu G. Infectious complications in the South African Black child with cancer. [unpublished dissertation]. WIReDSpace: University of the Witwatersrand; 2016. Available from: http://hdl.handle.net/10539/22523
  28. Van de Wetering MD, Poole J, Friedland I, Caron HN. Bacteraemia in a paediatric oncology unit in South Africa. Med PediatrOncol. 2001;37(6):525–531. https://doi.org/10.1002/mpo.1246
  29. Mvalo T, Eley B, Bamford C, et al. Bloodstream infections in oncology patients at Red Cross War Memorial Children`s Hospital, Cape Town from 2012 to 2014. Int J Infect Dis [serial online]. 2018 [cited 2018 Sep 26]. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1201971218345247
  30. Mikulska M, Viscoli C, Orasch C, et al. Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. J Infect. 2014;68(4):321–331. https://doi.org/10.1016/j.jinf.2013.12.006
  31. Harris PNA, Peleg AY, Iredell J, et al. Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiellaspp (the MERINO trial): Study protocol for a randomised controlled trial. Trials. 2015;16:24. https://doi.org/10.1186/s13063-014-0541-9
  32. Castagnola E, Caviglia I, Pescetto L, Bagnasco F, Haupt R, Bandettini R. Antibiotic susceptibility of Gram-negatives isolated from bacteremia in children with cancer. Implications for empirical therapy of febrile neutropenia.Future Microbiol. 2015;10(3):357–364. https://doi.org/10.2217/fmb.14.144
  33. Eljaaly K, Enani MA, Al-Tawfiq JA. Impact of carbapenem versus non-carbapenem treatment on the rates of superinfection: A meta-analysis of randomized controlled trials. J Infect Chemother [serial online]. 2018 [cited 2018 Sep 26];24(11):915–920. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30197092
  34. Xiao G, Chen Z, Lv X. Chlorhexidine-based body washing for colonization and infection of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus: An updated meta-analysis. Infect Drug Resist. 2018;11:1473–1481. https://doi.org/10.2147/IDR.S170497
  35. Mutters NT, Mersch-Sundermann V, Mutters R, Brandt C, Schneider-Brachert W, Frank U. Control of the spread of vancomycin-resistant enterococci in hospitals. DtschÄrztebl Int. 2013;110(43):725–731. https://doi.org/10.3238/arztebl.2013.0725
  36. Faron ML, Ledeboer NA, Buchan BW. Resistance mechanisms, epidemiology, and approaches to screening for vancomycin-resistant enterococcus in the health care setting. J ClinMicrobiol. 2016;54(10):2436–2447.
  37. Govender NP, Patel J, Magobo RE, et al. Emergence of azole-resistant Candida parapsilosis causing bloodstream infection: Results from laboratory-based sentinel surveillance in South Africa. J Antimicrob Chemother [serial online]. 2016 [cited 2018 Oct 2];71(7):1994–2004. Available from: https://academic.oup.com/jac/article/71/7/1994/1751401
  38. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of Candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis [serial online]. 2016 [cited 2018 Sep 17];62(4):e1–e50. Available from: https://academic.oup.com/cid/article/62/4/e1/2462830
  39. National Collaborating Centre for Cancer. Neutropenic sepsis: Prevention and management of neutropenic sepsis in cancer patients [homepage on the Internet]. London: National Institute for Health and Clinical Excellence (UK); 2012 [cited 2018 Oct 19]. (National Institute for Health and Care Excellence: Guidance). Available from: http://www.ncbi.nlm.nih.gov/books/NBK299128/


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