ANNUAL SURVEILLANCE REPORT AND ANTIBIOTIC GUIDE Specialists 2018
01 CONTENTS A. ESKAPE Organisms KwaZulu Natal Region: January 2015 to December 2017... 02 1. Introduction... 02 2. Blood cultures... 05 3. Invasive candidiasis... 06 B. Respiratory tract pathogens... 08 1. Viral... 08 2. Bacterial... 10 C. Antibiotic dosages for upper respiratory tract infections... 11 D. Urinary tract pathogens... 12 E. Stool Pathogens... 13 H. Antibiotics:... 15 1. Dosages for Selected Antibiotics: Adults... 15 2. Dosages for Selected Antibiotics: Paediatrics... 17 3. Therapeutic Options for Treatment of ESBL positive Enterobacteriaceae... 19 4. Dosages for Prolonged infusions... 20 I. Therapeutic options for carbapenem-resistant Enterobacteriaceae (CRE)... 22 J. Infectious Diseases Update... 23 K. PCR Tests... 25
02 ESKAPE ORGANISMS KWAZULU NATAL REGION ESKAPE Organisms KwaZulu Natal Region: January 2015 to December 2017 Introduction The following microorganisms, forming the acronym ESKAPE CCC, have been listed among the most prioritized antimicrobial resistance threats, effectively escaping the currently available antimicrobial armamentarium: E: Enterococcus faecium (Vancomycin resistant) S: Staphylococcus aureus (Methicillin resistant) K: Klebsiella species A: Acinetobacter baumannii (Carbapenem resistant) P: Pseudomonas aeruginosa (Carbapenem resistant) E: Enterobacter species C: Clostridium difficile C: Carbapenem resistant Enterobacteriaceae C: Candida species Antimicrobial resistance (AMR) is a worldwide problem. New forms of AMR are crossing international boundaries and spreading between continents with ease and speed. World health leaders have described antibiotic resistant microorganisms as nightmare bacteria that pose a catastrophic threat to people in every country in the world. Antibiotic-resistant infections add considerable and avoidable costs to overburdened health care systems. AMR estimates are an integral component of any antimicrobial stewardship program, allowing for informed appropriate selection of empiric therapy in an institute based on local epidemiology.
03 DEFINITIONS Extended spectrum beta lactamase producing (ESBL Positive) Extended spectrum beta-lactamases (ESBL) are enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. Carbapenems (meropenem, doripenem, imipenem and ertapenem) are the antimicrobial agents of choice for infections caused by such organisms. Carbapenemase resistant Enterobacteriaceae (CRE) Carbapenem resistant Enterobacteriaceae (CRE) are Enterobacteriaceae that are resistant to the carbapenems. CRE are often resistant to multiple classes of antimicrobials substantially limiting treatment options. Infections caused by CRE are associated with high mortality rates. Many CRE possess carbapenemases (carbapenemase producing Enterobacteriaceae (CPE) which can be transmitted from one Enterobacteriaceae to another potentially facilitating transmission of resistance. Therapeutic options include combination therapy which can include colistin, tigecycline or any other antibiotic to which the organism is susceptible. Clostridium difficile: Clostridium difficile (C. difficile) infections can cause illness ranging from diarrhoea to antibiotic-associated colitis, which can be fatal. Risk factors include recent medical care and antibiotics. CRAc : carbapenem resistant acinetobacter CRPs : carbapenem resistant pseudomonas
04 This report summarizes Lancet Laboratories AMR annual estimates for 2015 through to 2017 for the Kwa Zulu Natal private sector. Percentage resistant isolates 80 70 60 50 40 30 20 10 0 0.3 0.1 0.2 13 9 8 54 50 50 29 26 23 34 36 35 2.2 0.9 1.7 10 1011 77 75 77 VREᵃ MRSAᵇ CRAc CRPsᵈ ESBL CREᵉ C. difficile Candida spp 2015 2016 2017 Figure 1: Multidrug resistant pathogens (all clinical specimen types) ᵃ VRE rates have remained low throughout the province over the last 3 years ᵇ MRSA rates have consistently decreased over the last 3 years ᶜ CRAc are high at 50%, as it has been over the last 3 years ᵈ, ᵉ There is an increase in CRPs and CRE over the last 3 years, which is of concern from a therapeutic as well as epidemiologic perspective Percentage ESBL positive isolates 60 50 40 30 20 10 0 49 51 50 31 32 27 28 29 Escherichia coliᵃ Klebsiella speciesᵇ Otherᵇ 2015 2016 2017 28 Figure 2: ESBL producing Enterobacteriaceae (all sites) ᵃ The progressive increase in ESBL positive E. coli is of concern, as E. coli are the most common cause of community-acquired urinary tract infections. ᵇ ESBL rates among other species, including Klebsiella species remains relatively unchanged over the last 3 years.
05 Figure 3: Carbapenem resistant Enterobacteriaceae (CRE) from clinical specimens 300 250 Number of isolates 200 150 100 130 258 285 50 0 2015 2016 2017 Year CRE continues to increase in the province, since the first isolate 5 years ago. Most CRE in KZN carry the NDM-1 enzyme. The most frequently isolated species are Klebsiella species and Serratia marcescens.
06 BLOOD CULTURES Table 1: The five most frequently isolated species from blood cultures, ranked in descending order, for 2015, 2016 and 2017 2015 2016 2017 1 E. coli a E. coli a E. coli a 2 Staphylococcus aureusklebsiella pneumoniae Staphylococcus aureus 3 Klebsiella pneumoniae Staphylococcus aureus Klebsiella pneumoniae 4 Candida species Candida species Candida species 5 Enterococcus species Pseudomonas Pseudomonas aeruginosa aeruginosa E. coli remains the most frequently isolated blood culture pathogen in 2017. See graph below for AMR patterns in these pathogens 86 86 Percentage resistant isolates 32 28 36 48 50 50 20 9 11 16 20 29 77 2015 2016 2017 ESBL pos E.coliᵃ ESBL pos Klebsiella pneumoniae MRSA Carbapenem resistant Pseudomonas aeruginosaᵇ Non-Candida albicans species ᵃ The increase in ESBL positive E. coli is of concern as E. coli are a common cause of community-acquired urinary tract infections ᵇ Increasing carbapenem resistance among Pseudomonas aeruginosa bacteraemic isolates is of concern. The empiric therapy for suspected Pseudomonas aeruginosa infections must be based on knowledge of the antimicrobial resistance patterns in your local institute. Suitable alternatives, in the private sector in KZN, include the following: piperacillin-tazobactam, amikacin, ceftazidime and cefepime, where > 70% of isolates still test susceptible to these agents. Among these bacteraemic isolates, 98% remain susceptible to colistin.
07 INVASIVE CANDIDIASIS Percentage 60 50 40 30 20 10 0 2015 2016 2017 Figure 1: Species distribution (%)of Candida isolates from sterile sites (blood cultures and catheter tips) ᵃ Candida albicans accounts for less than a quarter of all invasive candida isolates in this region ᵇ Candida parapsilosis is the most frequent species implicated, accounting for 50% of cases ᶜ Candida auris has emerged as the third most frequent non-albicans species causing invasive candidiasis in this region, accounting for 6 % of isolates. Percentage resistance 90 80 70 60 50 40 30 20 10 0 Fluconazole R Voriconazole R Echinocandin R 2015 2016 2017 Figure 2: Antifungal resistance among Candida species (non-albicans) (blood cultures and catheter tips) Overall, there appears to be a slight decrease in azole resistance since 2015. This trend must be monitored further, considering the increasing prevalence of the more resistant species, Candida auris In 2017, in KZN, there was a single Candida glabrata isolate with confirmed resistance to the echinocandins. Empiric therapy in patients with suspected invasive candidiasis in this region therefore includes either an echinocandin (caspofungin, anidulafungin or micafungin) or amphotericin B.
08 CANDIDA AURIS Candida auris has been reported to be the second most frequent cause of candida bloodstream infections in South Africa. This organism has been implicated in nosocomial outbreaks in various parts of the world. Of concern is its ability to develop resistance to multiple anti-fungal agents. In the SA private sector, most of the Candida auris bloodstream isolates were resistant to fluconazole and at least 50% to voriconazole as well. There has been no echinocandin resistance reported thus far. Number of isolates 50 45 40 35 30 25 44 20 15 27 10 5 0 1 2015 2016 2017 Figure 1 : Candida auris isolates from all specimen types in KZN, 2015 2017 In KZN, 72 Candida auris isolates have been detected since 2015, with most isolates causing invasive disease (65%). Candida auris accounted for 1 % of invasive candidiasis in 2016 and 6% in 2017.Most of the patients with Candida auris were admitted to intensive care units. Percentage resistance 100 80 60 40 20 0 0 22 100 100 Figure 2 : Antifungal resistance among Candida auris isolates in KZN, 2015 2017, all specimen types Among the KZN isolates, only 22% (16/72) were susceptible to voriconazole, while they were all resistant to fluconazole. All isolates tested susceptible to the echinocandins (caspofungin, anidulafungin and micafungin) and to amphotericin B. References Moodley K et al. Emergence of Candida auris in South Africa. 2017. Poster presentation at FIDDSA 2017. Erika Britz and Nelesh P Govender. Global emergence of a multi-drug resistant fungal pathogen, Candida auris. SAJID 2016, 31:3, 69-70
09 RESPIRATORY TRACT PATHOGENS Most respiratory tract infections are viral in aetiology, thus requiring no antibiotic therapy. The following figures highlight the common pathogens detected in KZN in 2017. Viral 900 800 700 600 500 400 300 200 100 0 895 614 536 455 405 363 315 246 201 192 172 Figure 1: Respiratory viruses plus Mycoplasma pneumoniae as detected on polymerase chain reaction (PCR) for 2017 ᵃ Rhinovirus was the most frequently detected viral respiratory pathogen. It was detected consistently throughout the year. It is associated with prolonged hospitalisation and increased risk for the development of asthma. ᵇ RSV was detected throughout the year, but infections peaked over February-April. A second smaller peak was noted over November-December 2016 ᶜ Adenovirus is an important pathogen in both children and adults, presenting with conditions ranging from conjunctivitis and pharyngitis to pneumonia and lifethreatening systemic infections. It occurs throughout the year. ᵈ Mycoplasma pneumoniae was the third most frequently detected organism indicating its importance as part of the differential diagnosis when presented with an atypical pneumonia. ᵉ, ᶠ The influenza season started with the detection of predominantly influenza A from June to August, followed by influenza B in the latter part of August and September
10 BACTERIAL Bacterial STREPTOCOCCUS PNEUMONIAE 237 288 302 HAEMOPHILUS INFLUENZAE HAEMOPHILUS PARAINFLUENZAE 873 847 1072 1059 1105 1104 0 200 400 600 800 1000 1200 2015 2016 2017 Figure 1 : Streptococcus pneumoniae, Haemophilus influenza and Haemophilus parainfluenzae isolated from all specimen types, from 2015 2017. The commonest bacterial pathogens are H. influenzae and Streptococcus pneumoniae. Haemophilus parainfluenzae is a commensal of the nasopharynx but has also been implicated in respiratory tract infections, such as pneumonia and sinusitis. The common bacterial respiratory pathogens H. influenzae and S. pneumoniae were susceptible to amoxyclavulanic acid (>99%). Less than 5% of S. pneumoniae isolates, from blood and all sites, were nonsusceptible to penicillin and quinolones. There was 20% macrolide resistance noted in bacteraemia pneumococcal isolates. This suggests that empiric therapy with a macrolide for suspected pneumococcal infection is NOT appropriate
11 Antibiotic dosages for upper respiratory tract infections Antibiotic dosages for upper respiratory tract infections A) Acute Pharyngotonsillitis Adults Paediatrics 1. Amoxicillin 500-1000 mg twice daily (alternately, 50 mg/kg/d once daily (maximum 3000mg) for 10 days. 50mg/kg/d once daily (maximum1000 mg) for 10 days. 2. If penicillin allergic: a) Azithromycin 1. Amoxicillin b) Clarithromycin 500 mg once daily for 3 days. 500 mg twice daily or 500 mg modified-release once daily for 10 days. B) AOM or ABRS Adults Paediatrics 1 g 8 hourly for 5 days. 10 20 mg/kg/d once daily for 5 days. 15 mg/kg/d divided into 2 doses, for 10 days. 80 90 mg/kg/d divided into 2 doses. <2years 7days >2 years 5days Amoxicillin-clavulanate Cefuroxime Cefpodoxime 2000 mg amoxicillin-125 mg clavulanate 12 hourly for 5 days. 1000 mg 12-hourly for 5 days. 400 mg 12 hourly for 5 days. 90 mg/kg/d 30 mg/kg/d divided into 2 doses. 16 mg/kg/d divided into 2 doses. <2 years 7 days >2 years 5 days 2. If penicillin allergic: a) Azithromycin 10 mg/kg once daily for 3 days. estolate b)clarithromycin c)erythromycin d)levofloxacin e)telithromycin f)gemifloxacin g)moxifloxacin 500 mg 12 hourly or 750 mg once daily for 5 days. 800 mg once daily for 5 days. 320 mg once daily for 5 days. 400 mg once daily for 5 days. 15 30 mg/kg/d divided into 2 doses for 5 days. 40 mg/kg/d divided into 4 doses for 5 days. 20 mg/kg/d once daily or divided into 2 doses for 5 days. Adapted from: Brink A, et al. Updated recommendations for the management of upper respiratory tract infections in South Africa. S Afr Med J 2015
12 Urinary tract pathogens Percentage E.coli urinary isolates 100 90 80 70 60 50 40 30 20 10 0 ESBL positive Ciprofloxacin S Nitrofurantoin S Fosfomycin S Ertapenem S 2015 2016 2017 Figure 1: Antimicrobial susceptibility trends of urinary E. coli isolates from 2015 2017 Antimicrobial resistance in the community has increased over the last decade. The inevitable consequence has been an increasing difficulty in treating common infections such as urinary tract infections. The most prevalent pathogen in this setting is E. coli. Almost 30% of urinary E. coli isolates were ESBL positive i.e. resistant to most beta-lactams and cephalosporins. Only 56% of these isolates tested susceptible to the quinolones. These isolates have remained susceptible to the urinary antiseptics, nitrofurantoin and fosfomycin. These are therefore useful options for the management of acute uncomplicated cystitis. Empiric therapy for patients with pyelonephritis should be guided by local antimicrobial susceptibility patterns, while a urine microscopy and culture will assist in further guiding appropriate effective therapy. Most isolates remain susceptible to Ertapenem. References Gupta K et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clinical Infectious Diseases 2011;52(5): e103 e120 Bryce A et al. Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: systematic review and meta-analysis. BMJ 016;352: i939; http://dx.doi.org/10.1136/bmj.i939
13 Stool pathogens KZN 2017 The most frequent aetiology for gastroenteritis is viral. These are self-limiting illnesses, which require supportive management only. Rotavirus is a seasonal viral agent causing gastroenteritis in the winter months in South Africa. In 2017 the season started in June and peaked in August. Rotavirus and Adenovirus 140 Number of positives 120 100 80 60 40 20 0 Figure 1 : Number of stool samples that tested positive for rotavirus and/or adenovirus in 2017, by month in KZN Number of isolates 45 40 35 30 25 20 15 10 5 0 Jan-17 Feb-17 Mar-17 Apr-17 May-17 Jun-17 Jul-17 Aug-17 Sep-17 Oct-17 Nov-17 Dec-17 Campylobacter species Salmonella species Figure 2 : Number of Salmonella species and Campylobacter species isolated in 2017, in KZN, by month.
14 The two most frequently isolated bacterial causes of diarrhoeal disease include the Campylobacter species and Salmonella species. These are most frequently detected in the summer months in South Africa. Stool testing should be performed for patients presenting with diarrhoea accompanied by fever, bloody or mucoid stools, severe abdominal cramping or tenderness, or signs of sepsis. Blood cultures should be obtained from infants <3 months of age, all patients with signs of septicemia and immunocompromised patients. Molecular testing (PCR) is available for diagnosis of viral and bacterial causes of diarrhoeal illnesses. Reference: Andi L Shane, Rajal K Mody, John A Crump, Phillip I Tarr, Theodore S Steiner, Karen Kotloff, Joanne M Langley, Christine Wanke, Cirle Alcantara Warren, Allen C Cheng, Joseph Cantey, Larry K Pickering; 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea, Clinical Infectious Diseases, Volume 65, Issue 12, 29 November 2017, Pages e45 e80, https://doi.org/10.1093/cid/cix669 Gary R Fleisher et al. Approach to diarrhoea in children in resource-rich countries. Uptodate Literature review current through: Dec 2017
15 Antibiotic Dosages: Dosages for Selected Antibiotics: Adults Antimicrobial class Antimicrobial agent Loading dose Dose Carbapenem Ertapenem 1 g daily (up to 1g bd) Imipenem 1 2g/day 6 8 hourly, infuse over 40 60 minutes Meropenem 1 2g 8 hourly, infuse over 30 minutes Doripenem 500mg 8 hourly, infuse over 60 minutes Aminoglycosides Gentamicin 5-6mg/kg/day, once daily Amikacin 15mg/kg/day, once daily Beta lactam beta lactamase combination Piperacillin- tazobactam 4.5g 6 hourly Glycylcycline Tigecycline 100mg 50mg 12hourly (higher doses may be considered) Polymyxin Colistin 9MIU IVI 4.5MIU 12 hourly Glycopeptides Lipopeptide Azoles Echinocandins Vancomycin Teicoplanin Daptomycin Voriconazole Caspofungin 6mg/kg 12hourly for 24 hours 70mg IVI on the first day 15 20mg/kg 12 hourly 6 12mg/kg 12 hourly x 3 5 doses followed by 6mg/kg daily 6 8(up to 12)mg/kg/day once daily 3-4mg/kg 12 hourly 50mg once daily thereafter Anidulafungin Micafungin 200mg IVI on the first day 1000mg once daily thereafter 100mg IVI once daily
16 Dosages for Selected Antibiotics: Paediatrics Antimicrobial class Antimicrobial agent Age Loading dose Dose Carbapenem Ertapenem 3 12 years >12 years 15mg/kg IV/IM 12 hourly 1g/day 1g/day IV/IM up to 14 days Imipenem Neonates (>1.5kg) 25mg/kg/dose 12 hourly in the 1st week of life, 8 hourly from 1 3 weeks and 6hourly thereafter Infants and children >3 months 15 25mg/kg 6 hourly, infuse over 30 minutes Meropenem >3months 10 20mg/kg/dose 8 hourly, infuse over 5 30 minutes >50kg As for adults Doripenem 15 20 mg/kg/dose 8 hourly Aminoglycosides Gentamicin 1 week 10 years 8mg/kg/day on 1st day 6mg/kg/day thereafter 10 years 7mg/kg/day on 1st day; 5mg/kg/day thereafter Gentamicin Neonates 1 week 10 years 25mg/kg/dose on 1st day 15mg/kg/dose daily 18mg/kg/dose daily thereafter >10 years 20mg/kg/dose on 1st day 15mg/kg/dose daily thereafter Beta lactam betalactamase inhibitor combination: Pipercailli/ tazobactam Neonates < 7 Days 8 28 days 100mg/kg/dose 12 hourly 100mg/kg/dose 8 hourly Infant < 6 months 150 300mg/kg/24 hours in 3 to 4 divided doses Infant > 6 months 300 400mg/kg/24 hours in 3 to 4 divided doses Glycylcycline Tigecycline 8 11 years (limited data) >12years (limited data) 1.5mg/kg/dose (max100mg/dose) 1.2mg/kg/dose 12 hourly 1mg/kg/dose 12 hourly
17 Dosages for Selected Antibiotics: Paediatrics (contd) Antimicrobial class Antimicrobial agent Age Loading dose Dose 5th Generation cephalosporin Ceftaroline (complicated skin infections and bacterial communityacquired pneumonia) 2 6 months >6 months <18 years: < 33kg >33kg 8mg/kg/dose 8 hourly 12mg/kg/dose 8 hourly 400mg/dose 8 hourly Polymyxin Colisitin Neonates < 7 days > days 5mg/kg/day 12 hourly 7.5mg/kg/day 8hourly Child 2.5 5mg/kg/day in 2 to 4 divided doses Glycopeptide Vancomycin <1 week 15mg/kg 10mg/kg 12 hourly <1 week - 1 Month 15mg/kg 10mg/kg 8 hourly >1 month 15mg/kg 6 hourly, infuse over 60 minutes Vancomycin Neonates 16mg/kg > 2months - 12 years < 10mg/kg 12 hourly for 3 doses 6 10mg/kg daily Lipopeptide Daptomycin (skin and skin structure infections) 2-6 years 7 11 years 9mg/kg daily 7mg/kg daily 12 17 years 5mg/kg daily Oxazolidinone Linezolid 10mg/kg 8 hourly, IV or PO Adapted from David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc, https://expertconsult.inkling.com/read/mcmillan-harriet-lane-handbookpediatricantimicrobial- 2nd/chapter
18 Dosages for ESBL positive Enterobacteriaceae Adapted from Bassetti M, etal. The Management of Multidrug-resistant Enterobacteriaceae. www.co-infectiousdiseases.com; 2016 Primary BSI/Pneumonia/Abdominal infection/urinary tract infection First-line therapy, where the Piperacillin -tazobactam (PTZ) MIC 16/4mg/l: ᵃ Piperacillin-Tazobactam 16/2 g every 24 h or, ᵇ Meropenem 1 g 6 hourly or, ᶜ Ertapenem 500mg 6 hourly or, ᵈ Imipenem 0.5 g 6 hourly or, Imipenem 1 g 8 hourly or, NB. For abdominal infection only ᵉ Tigecycline 50 mg 12 hourly Second-line therapy: Carbapenems i.v. + amikacin 15-20 mg/kg/day daily or tigecycline 50 mg 12 hourly Enterobacteriaceae with PTZ MIC>16/4mg/l and/or severe infection. ᵇ Meropenem 1 g 6 hourly or, ᶜ Ertapenem 500 mg 6 hourly or, ᵈ Imipenem 0.5 g 6 hourly, or imipenem 1 g 8 hourly NB. For urinary tract infections only ᶠ Carbapenems i.v. + amikacin 20 mg/kg/day daily a Piperacillin/tazobactam: loading dose (4.5g in 1 h) followed by maintenance doses with continuous infusion (16/2 g every 24 h). b Meropenem: loading dose (1 g over 1 h) followed by maintenance doses with continuous infusion (1 g every 6 h over 6 h). c Ertapenem: maintenance doses with continuous infusion (500 mg every 6 h over 4 h) d Imipenem: loading dose (0.5 or 1 g over 1 h) followed by maintenance dose with continuous infusion (0.5 g every 6 h or 1 g every 8 h over 2 h). f Tigecycline: loading dose (100 mg every 12 h) if tigecycline MIC 0.5 1mg/l. (See next section for dosage recommendations for prolonged infusions)
19 Prolonged infusion of beta lactam antibiotics The trend in increasing antimicrobial resistance and the dearth of new antibiotics necessitates the optimisation of beta lactam therapy. Since beta lactam antibiotics demonstrate time dependent killing of bacteria i.e. the time that free drug concentrations remain above MIC (ft>mic) becomes a better predictor of killing. When giving intravenously, beta-lactams can be administered by three basic strategies. The most prevalent is the traditional intermittent schedule, which involves infusion of each fraction of the daily dosage over a short time intervals, i.e., 5 to 60 min. When each fraction of the daily dosage is infused over three or more hours, this dosing strategy is referred to as prolonged or extended infusion. A review of the literature suggests that prolonged or extended dosing of beta lactam antibiotics would be most beneficial in patients with the serious infections. Dosages for Prolonged infusions Adapted from: Nicolau D, et al.continous and Prolonged Intravenous β-lactam Dosing: Implications for the Clinical Laboratory. Clin Microbiol Rev. 2016 Oct;29(4):759-72. doi: 10.1128/CMR.00022-16.2016 Oct;29(4):759-72. Infusion Antimicrobial agent Creatinine clearance Dose Dosing interval time Piperacillin - tazobactam >20 ml/min 3.375 or 4.5 g Every 8 hours 4 hours 20 ml/min or intermittent HD or PD 3.375 or 4.5 g Every 12 hours 4 hours CRRT 3.375 or 4.5 g Every 8 hours 4 hours Cefepime 50 ml/min 2 g Every 8 hours 4 hours 30 to 49 ml/min 2 g Every 12 hours 4 hours 15 to 29 ml/min 1 g Every 12 hours 4 hours <15 ml/min or intermittent HD CRRT 1 g 2 g Every 24 hours 4 hours Every 12 hours 4 hours Meropenem < 50 ml/min 1 or 2 g Every 8 hours 3 hours 25 to 49 ml/min 1 or 2 g Every 12 hours 3 hours 10 to 24 ml/min 500 mg or 1 g Every 12 hours 3 hours <10 ml/min or intermittent HD CRRT 500 mg or 1 g 1 or 2 g Every 24 hours, given after HD Every 12 hours 3 hours 3 hours
20 Antimicrobial agent Creatinine clearance Dose Dosing interval Infusion time Imipenem >70 500 mg or 1 g Every 6 hours 3 hours 41 to 70 500 mg or 750 mg Every 8 hours 3 hours 21 to 40 250 or 500 mg Every 6 hours 3 hours 6 to 20 or intermittent HD or PD 250 or 500 mg Every 12 hours 3 hours CRRT 500 mg Every 6 hours 3 hours Doripenem 50 ml/min 500mg Every 8 hours 4 hours 1 hour for 30 to 50 ml/min 250mg Every 8 hours nosocomial pneumonia, 10 to 30 ml/min 250mg Every 12 hours complicated intraabdominal infection/uti (including pyelonephritis) HD: haemodialysis; PD: peritoneal dialysis; CRRT: continuous renal replacement therapy; MIC: minimum inhibitory concentration; CVVHDF: continuous venovenous hemodiafiltration
21 Therapeutic options for carbapenem-resistant Enterobacteriaceae (CRE) Risk level, Therapy type and Isolatesusceptibility 1. Susceptible to a beta lactam 2. Resistant to all beta lactams, susceptible to at least 2 drugs, including colistin 3. Resistant to all beta lactams and colistin, susceptible to at least 2 drugs 4. Pan drug resistant or susceptible to only one drug Drugs Backbone Meropenem (If MIC < 8mg/l) or 1 Ceftazidimeavibactam or Ceftazidime Colistin Tigecycline or aminoglycoside Meropenem plus ertapenem, or ceftazidime avibactam Drugs Accompanying drug/s Colistin, or tigecycline, or aminoglycoside N.B. If the backbone drug is intermediate, consider using 2 of these with backbone Tigecycline, or aminoglycoside Tigecycline, or aminoglycoside Add any active drug; consider investigational drugs if available Ceftazidime-avibactam availability in South Africa to be announced Table adapted from Rodríguez-Baño J et al, April 2018. Treatment of infections caused by extended-spectrum-beta-lactamase-, AmpC-, and carbapenemase producing Enterobacteriaceae. Clin Micro Reviews
22 INFECTIOUS DISEASES UPDATE A.MALARIA TREATMENT UPDATE: Artesunate has replaced quinine as the treatment of choice for severe malaria and has been available from October 2017 as the registered product GARSUN. The Section 21 application and reporting is no longer required. Compared to parenteral quinine, artesunate reduces death from severe malaria by 39% in adults and 24% in children. Advantages: 1) Rapid antimalarial action with activity against early to late stages of the parasite life cycle, preventing sequestration of parasite-infected red cells, and attendant complications. 2) Administration as a slow intravenous injection over several minutes rather than a slow rate-controlled intravenous infusion over 4-6 hours. 3) A favourable safety profile and without causing hypoglycaemia 4) No dosage adjustment in renal failure. Artesunate can be used in all trimesters of pregnancy, and there is no lower age or weight limit. It can also be administered intramuscularly if intravenous administration not possible. Dosage of artesunate is 2.4 mg/kg for patients weighing >20 kg stat, and again at 12 and 24 hours, and then once daily until patients can take oral treatment. For patients weighing <20 kg, the dose is 3 mg/kg stat following the same schedule. Artesunate must be given for at least 24 hours (i.e. 3 doses), and should be followed by a full course of artemether-lumefantrine (Coartem ) to avoid recrudescence. MALARIA PROPHYLAXIS The past 2016/2017-malaria season in southern Africa was particularly busy and made local and international news. Malaria preventive measures include chemoprophylaxis with mefloquine, doxycycline, or atovaquone/proguanil, which should be taken strictly according to pharmacist instructions. Mosquito bites may be prevented by washing clothes in pyrethroid insecticides, covering exposed areas especially at dawn and dusk by wearing long sleeves and pants, using mosquito nets and mosquito repellent, and staying indoors between dusk and dawn. Chemoprophylaxis is not 100% effective and travelers to malaria areas must be alert for the development of symptoms on return. Symptoms of malaria include fever, malaise, headaches and extreme tiredness. Danger signs are drowsiness, deep heavy breathing, yellow eyes, inability to eat or drink, and vomiting. Returned travelers, and residents in malaria-endemic areas that experience these symptoms should be investigated for malaria urgently. For more information on malaria in South Africa please visit www.nicd.ac.za Source: Division of Public Health, Surveillance and Response, NICD-NHLS ( outbreak@nicd.ac.za)
23 LISTERIA An update on the outbreak of Listeria monocytogenes outbreak, South Africa, 2018 As of 20 February 2018, 915 laboratory-confirmed listeriosis cases have been reported to NICD since 01 January 2017 (Figure 1). Most cases have been reported from Gauteng Province (59%, 541/915) followed by Western Cape (12%, 112/915) and KwaZulu-Natal (7%, 66/915) provinces. Cases have been diagnosed in both public (64%, 587/915) and private (36%, 328/915) healthcare sectors. Diagnosis was based most commonly on the isolation of Listeria monocytogenes in blood culture (73%, 669/915), followed by CSF (22%, 198/915). Where age was reported (n=886), ages range from birth to 92 years (median 20 years) and 41% (361/886) are neonates aged 28 days (Figure 2). Of neonatal cases, 97% (351/361) had early-onset disease (birth to 6 days). Females account for 56% (499/886) of cases where gender is reported. Final outcome data is available for 67% (617/915) of cases, of which 28% (172/617) died. This suggests that most cases in this outbreak have been exposed to a widely available, common food type/source. The most likely source of the current outbreak has been determined. Further information on Listeria treatment and prevention is available on our Lancet newsletter or via the NICD website ( www.nicd.ac.za) Source: Centre for Enteric Diseases, and Division of Public Health Surveillance and Response, NICD-NHLS
24 PCR Tests Diagnosis of infectious diseases has shown significant advancements from serologic and culture-based methods to molecular methods, viz. PCR (polymerase chain reaction). The following are some of the tests offered at lancet laboratories: Test Organisms Bacteria Viruses Fungal/ Protozoal PCR respiratory panel Mycoplasma pneumoniae Adenovirus Bordetella pertussis/ paratertussis Chlammydia pneumoniae Enterovirus Human coronavirus Human metapneumovirus Influenza A/b Parechovirus Parainfluenza virus Rhinovirus RSV MERS-Cov PCR meningitis panel Eschericia coli HSV-1 cryptococcus Group B streptococcus HSV-2 Listeria monocytogenes VZV Haemophilus influenzae CMV Neisseria meningitidis HHV6 Streptococcus pneumoniae parecho PCR gastro panel Campylobacter coli/jejuni Adenovirus F&G Cryptosporidium Salmonella species Astrovirus Entamoeba histolytica Shigella species Norovirus Giardia intestinalis plesiomonas Rotavirus cyclospora Yersinia entercolitica Sapovirus C.difficle E.coli PCR urethritis panel TB PCR PCR carbapenemase Chlamydia trachomatis Mycoplasma hominis Mycoplasma genitalium Neiserria gonorrhoea Ureaplasma parvum Ureaplasma urealyticum TB NDM-1, KPC, OXA-48, IMP, VIM, GES Trichomonis vaginalis
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