Which are the best antibiotics to use? It is a fallacy to think that broad spectrum antibiotics are better because they cover more organisms. On the contrary, for that very reason they are more potent at selecting for resistant organisms. In a hugely important study in neonatal units in the Netherlands, de Man et al1
showed that empiric therapy using the “narrow spectrum” antibiotics, penicillin and tobramycin, was significantly less likely to select for resistant organisms than using “broad spectrum” amoxycillin and cefotaxime.
Almost all experts agree that the best empiric regimen for neonates is a penicillin or semisynthetic penicillin together with an aminoglycoside.17
The choice of the penicillin will depend on the organisms causing sepsis. If it is necessary to cover for staphylococci, then oxacillin, cloxacillin, or flucloxacillin may be most appropriate.17
In developing countries, it may be necessary to cover for staphylococci from birth, whereas staphylococcal infections are rare in industrialised countries before the third day of age.21
Empiric vancomycin is not necessary unless MRSA is common,17
and it is important to restrict vancomycin use in all countries because of the risk of selecting for vancomycin resistant organisms. The choice of aminoglycoside also depends on local data. If the colonising and infecting bacteria in a neonatal unit all become resistant to gentamicin, for example, they may become sensitive again after a prolonged period using an aminoglycoside to which they are sensitive—for example, netilmicin.22
In some countries, the organisms colonising babies from birth have high rates of antibiotic resistance, suggesting that community antibiotic use has resulted in the mothers being colonised with resistant organisms.14
The antibiotics of choice for early onset neonatal sepsis will then need to be tailored to cover the likely organisms—for example, it may be necessary to use empiric flucloxacillin and netilmicin for suspected early sepsis if there are high rates of early onset infection with S aureus
and with gentamicin resistant Gram negative bacilli.
Using antibiotics in rotation has been effective in some settings in reducing resistance.23
However, most developed countries now place restrictions on which antibiotics may be used and when, and such restrictions have been shown to reduce antibiotic resistance. In a study from Brazil, neonatal unit healthcare associated infections were reduced from 32% to 11% after education and restriction of the use of cephalosporins.25
How does one change antibiotics, if most of the babies on a neonatal unit are already colonised with one or more multiresistant organisms? One way would be to separate (or “cohort”) the babies currently on the unit from any new admissions. The babies colonised with the resistant organisms—for example, MRSA—would be given the appropriate antibiotics (in this case vancomycin with gentamicin) if they developed suspected sepsis. The new admissions would be given flucloxacillin and gentamicin. Provided that the new admissions are protected, by hand washing and good hygiene, from the babies colonised with resistant organisms, it should be possible to introduce “narrow spectrum” antibiotics and continue their use once all babies colonised with resistant organisms are discharged.
Ten point plan to reduce antibiotic resistance in neonatal units
- Always take cultures of blood (and perhaps cerebrospinal fluid and/or urine) before starting the infant on antibiotics.
- Use the narrowest spectrum antibiotics possible, almost always a penicillin—for example, benzylpenicillin, flucloxacillin, piperacillin, ticarcillin—and an aminoglycoside—for example, gentamicin, netilmicin, amikacin.
- Do not start treatment, as a general rule, with a third generation cephalosporin—for example, cefotaxime, ceftazidime—or a carbapenem—for example, imipenem, meropenem.
- Develop local and national antibiotic policies to restrict the use of expensive, broad spectrum antibiotics.
- Trust the microbiology laboratory: rely on the blood culture results.
- Do not believe that abnormal results for a non‐specific test, such as a raised serum C reactive protein, means that the baby is definitely septic.
- If blood cultures are negative at two to three days, it is almost always safe and appropriate to stop antibiotics.
- Try not to use antibiotics for long periods.
- Treat sepsis, but not colonisation.
- Do your best to prevent nosocomial infection, by reinforcing infection control, particularly hand washing.