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Antibiotic Update 2011: Susceptibility Patterns and Guidelines for Antibiotic Use

Susceptibility Patterns and Guidelines for Antibiotic Use

This antibiotic review is based on the SASCM figures January to June 2010 and is a guideline to the use of antibiotics for common pathogens. Please note the high numbers of ESBL producing organisms and MRSA's.

Treatment of Gram Positive Infections

Staphylococcus aureus

Cloxacillin remains the drug of choice for all S. aureus infections where the isolate is deemed to be clinically significant. The percentage of methiillinresistant Staphylococcus aureus (MRSA) strains during early 2010 was 20%in Johannesburg and 15% in Pretoria. Resistance is detected in both hospital and community acquired isolates, the latter appear to be on the increase. The highest burden of MRSA's is found in long-term care facilities, chronic care patients, trauma units and large ICU's. These MRSA's are usually multi-resistant and treatment is often limited to the glycopeptides and to linezolid. All of our reported S.aureus cultures are vancomycin, teicoplanin and linezolid susceptible. However there are reports of resistance to all 3 antibiotics but to date this is not a problem in S.A.

% methicillin resistance in S. aureus

  JHB PTA DBN
S. aureus 20 15 18

Coagulase Negative Staphylococci (CNS)

S. epidermidis cultures are very often methicillin-resistant. 51% in Johannesburg, 60% in Pretoria and 64% in Durban are MRSE's. Most CNS isolates are skin contaminants. In patients with serious infections eg infected prosthesis, endocarditis or in a patient with line sepsis the empiric therapy would therefore be vancomycin, teicoplanin or Linezolid. Resistances to these antibiotics are gradually increasing and treatment should be based on antibiogram. Please de-escalate if sensitivity of strain is known.

S. pneumoniae

Penicillin resistance occurs because of changes in the penicillin-binding proteins, resulting in decreased affinity and consequently a stepwise resistance to penicillin. At a low MIC, this resistance can be overcome by increasing the dose of the beta-lactam antibiotic. Closed infections such as meningitis require higher levels of antibiotic to achieve adequate levels in the infected area. Thus higher MIC breakpoints are used for CSF specimens than for lower respiratory tract specimens and bloodstream infections.

% Susceptibility of S. pneumoniae in isolated from the CSF

  JHB PTA DBN
n = Total number of isolates 9 5 5 9 5 5
Penicillin~ Susceptible 66.6 80 20
Resistant 33.3 20 80
3rd generation cephalosporins (parenteral)* Susceptible 100 100 100
Resistant 0 0 0

The recommended empiric treatment for suspected pneumococcal meningitis remains third generation cephalosporins. In the event of intermediate cephalosporin resistance from a CSF isolate, the maximum dose of Ceftriaxone (Adult 4 gm daily, Paediatric 50-75mg/kg daily) / Cefotaxime (Adult 4gm daily, Paediatric 50mg/kg/dose 6 hourly) should be used in combination with another agent eg Vancomycin or Rifampicin. In the event of a fully
resistant isolate from the CSF, although none have been reported locally, vancomycin is the drug of choice.

Pneumococci isolated from the upper and lower respiratory tracts

In isolates from the upper and lower respiratory tract displaying intermediate resistance to penicillin and / or third generation cephalosporins, resistance can be overcome by dosing maximally with the chosen beta-lactam agent. Erythromycin sensitivity in LRT specimens has been below 50% during the past few years. Levofloxacin and Moxifloxacin and Telithromycin are still 100% susceptible.

% Susceptibility in Pneumococci isolated from the URT

  JHB PTA DBN
Penicillin~ Susceptible 99 100 96
IR 1 0 4
HR 0 0 0
Erythomycin   48 57 58
Telithromycin 100 100 100
3 generation cephalosporins Susceptible 99 96.5 100
IR 1 2.5 0
HR 0 1 0
Moxifloxacin 100 100 100

% Susceptibility in Pneumococci from LRTI isolates

  JHB PTA DBN
Penicillin~ Susceptible 99 100 100
IR 1 0 0
HR 0 0 0
Erythomycin - susceptible   50 51 52
Telithromycin 100 100 100
3 generation cephalosporins Susceptible 99 96.5 100
IR 1 3 0
HR 0 0.5 0
Moxifloxacin 100 100 100

Please note the big increase of pneumococcal susceptibility to penicillin due to the change in Laboratory guidelines and testing.

% Susceptibility in Pneumococci from Blood cultures

  JHB PTA DBN
Penicillin~ Susceptible 100 100 100
IR 0 0 0
HR 0 0 0
Erythomycin   72 71 88
Telithromycin 100 100 100
3 generation cephalosporins Susceptible 100 100 100
IR 0 0 0
HR 0 0 0
Moxifloxacin 100 100 100

Treatment of Gram Negative Infections

Extended spectrum beta-lactamase' (ESBL) Production

ESBL's are genes carried on a plasmid and thus easily transferable to other enterobacteriaciae. The ESBL's been first isolated in Klebsiella spp but have rapidly spread to all the enterobacteriaciae. These bacteria are resistant to ampicillin, all cephalosporins including the 4th generation cephalosporins and pipericillin/tazobactam. Empiric therapy includes the carbapenems. Ciprofloxacin may be used if susceptible on testing. Infection control measures should be in place for all ESBL positive organisms. Carbapenem resistance has been seen in ESBL positive organisms due to KPC production. Ertapenem is used as a screen for this enzyme. If resistance to all the carbapenems is reported, Tigecycline might be a option for treatment.

% ESBL Production

  JHB PTA DBN
Klebsiella spp 54 47 45
Enterobacter spp 20 15 14
E. coli 20 6 11

Be aware that more than half of all the klebsiella isolates are ESBL positive in Gauteng.

% susceptibility in Klebsiella pneumoniae from Blood Cultures

  JHB PTA DBN
Cefuroxime 40 42 35
Ceftriaxone 42 43 36
Cefepime 42 43 36
Piperacillin /Tazobactam 55 40 58
Ciprofloxacin 57 56 64
Amikacin 79 74 83
Ertapenem 99 100 100
Imipenem / Meropenem 10 100 100

% susceptibility in E. coli from Blood Cultures

  JHB PTA DBN
2nd generation cephalosporins 82 79 72
3rd generation cephalosporins 86 83 75
Amox / clavulanate 76 70 76
Ciprofloxacin 63 70 59
Piperacillin/tazobactam 85 76 86
Amikacin 92 87 87
Imipenem/Meropenem 100 100 100

% susceptibility in E. coli from Urine

  JHB PTA DBN
Ampicillin 27 31 21
2nd generation cephalosporins 91 91 87
Amox / clavulanate 84 78 84
Ciprofloxacin 77 77 77

Empiric Treatment of community acquired Urinary Tract Infections

Empiric choice of antibiotics in treating a community-acquired UTI remains Augmentin or a 2nd generation cephalosporin. Please note that 23% of E. coli from the urinary tract are resistant to ciprofloxacin and that it should be used with this in mind when it is used empirically.

Another option for the treatment of uncomplicated lower urinary tract infections only, where the organism retains susceptibility, is fosfomycin which is a urinary antiseptic. Macrodantin is unfortunately at this time not available in South Africa.

% Susceptibility in Acinetobacter spp from Blood Cultures

  JHB PTA DBN
Ceftazidime 20 25 25
Cefepime 37 43 48
Pip/tazobactam 19 20 18
Ciprofloxacin 32 41 58
Amikacin 55 52 90
Tobramycin 55 70 80
Meropenem 38 39 58
Imipenem 37 41 58

Acinetobacter spp are opportunists and may cause serious infections in immuno-compromised hosts. A multi-resistant strain is present in many of the Gauteng Hospitals. Treatment must be according to the antibiogram. Tobramycin and/or colistin often remain the only susceptible antibiotics. Please note that strict infection control measures should be in place for all pan-resistant acinetobacters and pseudomonas

Pseudomonas auruginosa

There are some strains in the Gauteng region that are fully resistant. Colistin and aztreonam are routinely tested but there are practical problems with both antibiotics and some strains are resistant especially to aztreonam. In view of the rapidly increasing ESBL problem, the carbapenems have become empiric choice in many ICU patients with suspected nosocomial gram-negative infections. Remember that some pseudomonas strains have isolated imipenem / meropenem resistance and that ertapenem has no activity against non-fermenting organisms (pseudomonas, acinetobacter and stenotrophomonas).

% Susceptibility P. aeruginosa from Blood Cultures

  JHB PTA DBN
Ceftazidime 83 66 58
Cefepime 80 67 58
Pip/tazobactam 69 51 17
Amikacin 78 73 79
Meropenem 77 59 85
Imipenem 72 55 79
Ciprofloxacin 67 64 73

Amp c

Certain organisms eg enterobacter, serratia, citrobacter, morganella and providencia spp. have a chromosomal gene that induces resistance to the 1st, 2nd and 3rd generation cephalosporins as well as ampicillin. Therefore the above mentioned antibiotics are not recommended for these bacteria. Empiric therapy for all Amp c producing bacteria includes quinolones, the 4th generation cephalosporins (cefepime) or the carbapenems (meropenem, imipenem and ertapenem)

% Susceptibility in Enterobacter spp from Blood Cultures

  JHB PTA DBN
Cefepime 62 86 69
Piperacillin/tazobactam 71 37 74
Amikacin 90 88 83
Meropenem/Imipenem 99 100 100
Ertapenem 98 100 100
Ciprofloxacin 85 92 87

Reference:

  1. South African Society for Clinical Microbiology (SASCM) Private Susceptibility Data January to June 2010

Download this article in PDF format - Antibiotic Update 2011 Newsletter July 2011