Antibiotic prescribing patterns in a neonatal intensive care unit

Original Research: Antibiotic prescribing patterns in a neonatal ICU

Antibiotic prescribing patterns in a neonatal intensive care unit N Schellack, AGS Gous

Natalie Schellack, Andries Gous, Department of Pharmacy, Faculty of Health Sciences, University of Limpopo (Medunsa Campus). Correspondence to: Dr Natalie Schellack, Department of Pharmacy, Faculty of Health Sciences, University of Limpopo (Medunsa Campus). E-mail: [email protected]

An outbreak of invasive candidiasis in the neonatal intensive care unit (NICU) of the Dr George Mukhari Academic Hospital in Ga-Rankuwa necessitated evaluation of the antibiotic prescribing practices in the unit. A selective randomised sample of 100 patients was followed up over a nine-month period to evaluate prescribing patterns. The existing antibiotic policy was used to compare the prescription practices and use of antibiotics. The frequency of use, number of antibiotics per patient and duration of use were documented. Of the 100 patients followed, 95 were prescribed intravenous antibiotics. All prescribed antibiotics for 77 patients are listed in the antibiotic policy. Nineteen different antibiotics were prescribed, and 11 of the 19 prescribed antibiotics appear in the antibiotic policy. Most patients received more than two antibiotics during their stay, as the average number of antibiotics used per patient during the study period was 3.4. The average duration of use for all antibiotics, except cefepime and ceftriaxone, was for longer than seven days. Although antibiotics were used according to the ward protocol in the majority of patients, deviations from the protocol were associated with patients’ clinical condition and/or results from blood cultures. The duration of antibiotic use needs to be monitored to prevent unnecessary prolonged use, as in this investigation. An antibiotic policy may be useful to guide and measure rational antibiotic therapy in a NICU. South Afr J Epidemiol Infect 2011;26(4)(Part II):267-270

Peer reviewed. (Submitted: 2010-07-09. Accepted: 2011-02-25.) © SAJEI

Introduction

The organisms listed above are prone to cause septicaemia in neonates and infants less than two months of age. Antibiotic regimens would commonly include broad-spectrum penicillins, such as ampicillin or amoxicillin, often combined with an aminoglycoside or a third-generation cephalosporin to provide empirical cover against the organisms listed above.2

An outbreak of invasive candidiasis in the neonatal intensive care unit (NICU) of the Dr George Mukhari Academic Hospital in Ga-Rankuwa prompted the management of the hospital to launch an investigation. Candida spp. is an increasingly common cause of mortality and morbidity in preterm infants.1 Risk factors associated with acquiring Candida infections were investigated. These included, but were not limited to, gestational age, low birthweight, length of hospital stay and prolonged broad-spectrum antibiotic use.1 The antibiotic factors investigated included frequency of use, number of antibiotics per patient and duration of use. Apart from the development of Candida infections, use of broad-spectrum antibiotics is also associated with the emergence of antibiotic resistance. This emergence of resistance associated with antibiotic use has been recognised by various authors.2,3 Empiric broad-spectrum antibiotics are often administered in NICU if infections are suspected. The empiric antibiotic regimens chosen for suspected infections in the NICU should include coverage of: • Group B streptococci (Streptococcus agalactiae) • Listeria monocytogenes • Escherichia coli • Haemophilus influenzae.

South Afr J Epidemiol Infect

According to Gould,4 there is little doubt that the implementation of an antibiotic policy is effective in both reducing the costs of antibiotics and the prevalence of resistance. The NICU has an antibiotic policy (refer to Table I) which was developed by the Department of Paediatrics and Child Health and approved by the Antibiotic Committee of the hospital. The purpose of this article was not to evaluate the antimicrobial protocol as such, but to measure the antimicrobial prescribing patterns and use against the existing antimicrobial policy.

Methods Following the outbreak of invasive candidiasis, an investigation was conducted as part of a larger study which determined the need for pharmaceutical care in the NICU. The aim of this investigation, which was conducted upon request from hospital management, was to record the antibiotic prescribing patterns and to compare them with the current antibiotic policy. (Refer to Table I).

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Study site

Table I: Antibiotic policy as adapted from ward protocol

The study was conducted in the NICU of Dr George Mukhari Hospital, a public sector teaching hospital situated in GaRankuwa, north of Pretoria, South Africa. The NICU is a 76-bed unit which is part of the paediatric corridor. It is subdivided into the following sections: • Intensive care unit • High care unit • Kangaroo mother care unit (KMCU) • Isolation • Heating rooms. Sample population and sampling

A total of 1,041 patients were admitted to the NICU during a ninemonth study period (22 January to 21 September 2007). During this time, there were 882 discharges and 159 deaths, and a ward occupancy rate of 107.2%.5 Data sets of 100 patients admitted to the intensive care section of the NICU, which were used for the larger pharmaceutical care study, were retrospectively reviewed to determine the antibiotic prescribing patterns. The patients were selected using systematic sampling, where every 10th patient was used, until a sample of 100 patients was recruited.

Description

Antibiotic (dose and duration)

Duration of empiric antibiotic therapy

Treat for 7 days (stop antibiotics if cultures are reported negative) Exceptions: • Congenital syphilis • Confirmed meningitis

First-line therapya

• Amikacin 25 mg/kg stat, then 20 mg/kg daily IVI • Penicillin G 100,000 IU/kg per dose given 12 hourly IVI Notes: • Amikacin levels must be checked • Do not administer amikacin if renal function is impaired

Second-line therapya

• Piperacillin/tazobactam 50 mg/kg per dose given 8 hourly IVI When Staphylococcus infection is suspected/ reported add: teicoplanin 16 mg/kg loading dose on day 1 and then 8 mg/kg daily; if teicoplanin is not available, use vancomycin

Third-line therapya

• Meropenem 20 mg/kg per dose given 12 hourly IVI For meningitis: • Meropenem 40 mg/kg per dose given 8 hourly IVI If meropenem is not available, use imipenem

Fourth-line therapya

• To be discussed with consultant on duty • Ciprofloxacin 10-20 mg/kg per day in 12 hourly doses IVI

For suspected meningitisa

Initiate ampicillin and cefotaxime until culture results are available • ≤ 7 days old -- Ampicillin 50 mg/kg per dose PLUS -- Cefotaxime 50 mg/kg per dose given 12 hourly IVI • > 7 days old -- Ampicillin 100 mg/kg per dose given 8 or 12 hourly IVI PLUS cefotaxime 50 mg/kg per dose given 8 hourly IVI

Important

Ceftriaxone can only be administered if the bilirubin levels are not increased After intra-abdominal surgery, add metronidazole, except if already on piperacillin/tazobactam or carbapenem Fungal infections must be considered in patients who do not respond to antibiotics, despite adequate doses

For Klebsiella infection

Single therapy is sufficient

For Pseudomonas infection

Use a sufficient combination of any of the following antibiotics, according to the reported antibiotic sensitivity results, together with an aminoglycoside: • Piperacillin/tazobactam • Meropenem • Imipenem • Ciprofloxacin • Cefepime Discuss with the consultant on duty

Data collection

Patient demographics (gestational age and birthweight) and duration of hospital stay were recorded. Antimicrobial prescribing patterns were followed for each patient for the duration of their hospital stay. The following were recorded to evaluate antimicrobial prescribing patterns: • Duration of administration • Sensitivity patterns (for methicillin-resistant Staphylococcus aureus [MRSA]) • Antibiotic prescribed • Was the antimicrobial prescribed according to the ward protocol? As part of pharmaceutical care, non-adherence to the policy in combination with patient factors was discussed within the multi-disciplinary team. The multi-disciplinary team included a paediatrician (consultant) and registrars, a clinical pharmacist and nursing staff. These interventions and decisions were recorded for research purposes. Ethical considerations

Patients who do not respond to antibiotics, despite adequate doses, must be considered to have fungal infections

The institution’s ethics committee approved the larger study and all data collected and analysed formed part of this study. Full confidentiality and individual rights were maintained during the study period. No patients were named in presenting the data.

a

Repeat cultures and stop antibiotics if cultures reported negative

(range 22-42 weeks; n=100 patients).The mean birthweights are summarised in Table II.

Results

The mean duration of stay in the NICU for all patients was 29.8 days (range 1 to 108 days; n=100).Of the 100 patients

The average gestational age at birth was 33.0 ± 4.3 weeks


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Table II: Birthweights of the study population

Number Mean birthweight (g)

Female

Male

Ambiguous

All

45

54

1

100

1,753.3

1,623.1

2,750.0

1,693.0

Number of patients

Gender

Median

1,600

1,575

1,600

Range

600-3,300

800-3,800

600-3,800

followed, 95 patients were prescribed intravenous antibiotics. Five patients did not receive any antibiotics and were excluded from the study. All prescribed antibiotics for 77 patients (81%) are listed in the antibiotic policy. Nineteen different antibiotics were prescribed and are listed in Table III. Eleven of the 19 prescribed antibiotics appear in the antibiotic policy. Fiftyeight per cent of the antibiotics were administered for 10 days or longer. In one instance both amikacin and piperacillin/ tazobactam were administered for 36 consecutive days to a patient. Amikacin was also administered for 35 and 23 (consecutive) days to two other patients. Ciprofloxacin was administered for 25 consecutive days to two patients and 23 (consecutive) days to a third patient.

Number of antimicrobials received

Figure 1: Number of antibiotics per patient (N=95)

Discussion The main aim of this study was to evaluate prescribing patterns of antibiotics against the existing antibiotic protocol, as irrational use of antibiotics has been identified as a risk factor for invasive candidiasis.1,6,7

The eight antibiotics not included in the antibiotic policy were cefoxitin, ceftazidime, cefuroxime, cloxacillin, co-trimoxazole, erythromycin, gentamicin and tobramycin. Although these eight Most patients received more than two antibiotics during their antibiotics were not included in the antibiotic policy, they were stay in the NICU. The average number of antibiotics used per given based on individual clinical assessment. Cefoxitin was patient during the study period was 3.4. Figure 1 depicts administered as prophylaxis in a neonate undergoing colorectal the number of antibiotics prescribed per patient during their surgery. Ceftazidime was prescribed for a patient with positive hospital stay. Three hundred and nineteen antibiotics were blood cultures for Acinetobacter baumannii and Pseudomonas prescribed for the 95 patients. aeruginosa. Cefuroxime was used in two patients with pneumonia. In one patient it was only administered for two days Table III: Antibiotics prescribed, number of patients and duration of antibiotics before it was changed to ceftazidime after isolation of an A. baumannii. Cloxacillin was administered In Number of Duration of use (days) in skin infections, as empirical treatment when Antibiotic agent antibiotic patients cultures were still pending. Co-trimoxazole was policy N = 95 Average Minimum Maximum administered to a neonate who was exposed to Yes 66 11.0 2 36 Amikacin the HIV as prophylaxis for Pneumocystis jirovecii. Yes 6 10.8 6 15 Ampicillin Erythromycin was used in 10 neonates where Benzylpenicillin Yes 48 8.6 2 20 atypical pneumonia was suspected. Gentamicin Yes 1 5.5 1 10 Cefepime was administered to six patients who required an Cefotaxime Yes 5 12.2 6 18 aminoglycoside following prior amikacin therapy. No 1 8.0 8 8 Cefoxitin Tobramycin was only administered in one neonate with multidrug-resistant A. baumannii. Ceftazidime No 8 11.9 9 16 Ceftriaxone

Yes

1

5.0

5

5

Cefuroxime

No

2

9.0

2

16

Ciprofloxacin

Yes

28

11.7

2

25

Cloxacillin

No

3

11.7

6

18

Co-trimoxazole

No

1

-

-

21

Erythromycin

No

10

9.4

3

14

Gentamicin

No

6

10.0

1

14

Metronidazole

Yes

13

12.0

2

22

Meropenem

Yes

47

9.8

2

25

Piperacillin/tazobactam

Yes

62

9.7

1

36

Tobramycin

No

1

10.0

10

10

Vancomycin

Yes

10

10.0

6

15


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An antibiotic policy is used in routine care, and deviation from policy is indicated in special clinical conditions. These deviations should be guided by cultures and clinical presentation. This was the case in all of the 18 patients who received antibiotics which were not part of the policy. These decisions were discussed within a multi-disciplinary team consisting of a paediatrician (consultant), registrars in paediatrics, a clinical pharmacist and the relevant registered nurse. Following the need for the use of antibiotics not listed on the protocol, it may be necessary to alter the

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the majority of these cases. Deviations from the protocol were based on patients’ clinical conditions and sensitivity results. Although the indication for use of most antibiotics could be justified, the prolonged use of some antibiotics was of concern. The duration of antibiotic use should be monitored and clearly specified in a protocol. Prolonged use may contribute to the development of antimicrobial resistance and invasive candidiasis. The outbreak of invasive candidiasis experienced in the NICU may have been the result of a combination of factors, which would necessitate further investigation. An antibiotic policy is useful in guiding antibiotic use, especially in a teaching hospital where medical personnel in training rotate through the NICU. Further, it may be useful to update the antibiotic policy to include those antibiotics that are not on the policy, but are being used regularly according to sensitivity patterns. An antibiotic policy is a living document and should be updated regularly.

antibiotic policy. The drugs listed above may be included in the policy for specific indications: • Cefoxitin: For colorectal surgery prophylaxis. • Ceftazidime: As an alternative for P. aeruginosa and A. baumannii. • Cloxacillin: For sensitive S. aureus skin infections. • Co-trimoxazole: For the prophylaxis of P. jirovecii – should preferably only be used from 6 weeks of age, due to an increased risk of developing kernicterus in the jaundiced neonate. • Erythromycin: For atypical infections – monitor for signs and symptoms of gastric intolerance, as infantile hypertrophic stenosis can result. • Gentamicin and tobramycin: In the event of amikacin resistance. The number of antibiotics administered per patient ranged from one to nine antibiotics during the course of their hospital stay. Further investigation should be done to determine a correlation between hospital stay and antibiotic use.

Acknowledgement The researcher was supported by an MRC internship grant.

The average duration of use for all antibiotics, except cefepime and ceftriaxone, was for longer than seven days. According to Labenne et al,3 before publication of national guidelines, most French neonatologists treated for seven days in cases of probable early-onset neonatal infection (EONI), for 10 to 14 days in cases of septicaemia, and for 14 to 21 days in cases of meningitis. The optimum duration of antibiotic therapy remains controversial and very few recommendations exist for use longer than 14 days, other than in infections such as meningitis and endocarditis. The maximum duration for 13 (68 %) of the antibiotics was longer than 14 days. Stricter policies should be in place to monitor the duration of use.

References

Ten patients received vancomycin, which was only instituted after MRSA was isolated from blood cultures sent to the laboratory.

Conclusion

Rodriguez D, Almirante B, Park BJ, et al. Candidemia in neonatal intensive care units: Barcelona, Spain. Pediatr Infect Dis 2006; 25(3): 224-229

2.

De Man P, Verhoeven BAN, Verbrugh, HA, Vos MC, Van den Anker JN. An antibiotic policy to prevent emergence of resistant bacilli. Lancet 2000; 355: 973-978

3.

Labenne M, Michaut F, Gouyon B, Ferdynus C, Guoyon J. A population-based observational study on restrictive guidelines for antibiotic therapy in early-onset neonatal infections. Pediatr Infect Dis 2007; 26(7): 593-599

4.

Gould IM. A review of the role of antibiotic policies in the control of antibiotic resistance. J Antimicrob Chemother 1999; 43: 459-465

5.

Statistical document of the Department of Paediatrics (NICU). Dr George Mukhari Hospital, 2007

6.

Chapman RL. Candida infections in the neonate. Curr Opin Pediatr 2003; 15: 97-102

7.

Chapman RL. Prevention and Treatment of Candida infections in neonates. Semin Perinatol 2007; 31(1): 39-46

8.

Benjamin DK, De Long ER, Steinbach WJ, Cotton CM, Walsh TJ, Clark RH. Empirical therapy for neonatal candidemia in very low birth weight infants. Pediatrics 2003; 543-547. Available at http://www.pediatrics.org/cgi/content/full/112/3/543 (Accessed: 16 September 2010)

9.

US Department of Health and Human Services, Health Resource Services Administration, Maternal Health Bureau. Gaining and Growing: Assuring nutritional care of preterm infants. 2007. [Website]. Acronyms, Definitions and Classification Systems (last revised 16/3/2007). Available at: http://depts.washington.edu/growing/About/Acronyms.htm (Accessed: 10 June 2010)

10. Merenstein GB, Gardner SL. Handbook of Neonatal Intensive Care. 5th ed. St Louis Mosby, Inc., 2002

Antibiotics were used according to the ward protocol in


1.

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