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LETTER TO THE EDITOR
Year : 2013  |  Volume : 12  |  Issue : 1  |  Page : 59-60  

Are penicillins still relevant for empirical treatment in contemporary pediatric therapeutics?


1 Department of Pediatrics, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria
2 Department of Pharmacy, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria

Date of Web Publication7-Mar-2013

Correspondence Address:
Richard Onalo
Department of Pediatrics, University of Abuja Teaching Hospital, Gwagwalada, Abuja
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1596-3519.108259

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How to cite this article:
Onalo R, Adeleke I S, Onalo V. Are penicillins still relevant for empirical treatment in contemporary pediatric therapeutics?. Ann Afr Med 2013;12:59-60

How to cite this URL:
Onalo R, Adeleke I S, Onalo V. Are penicillins still relevant for empirical treatment in contemporary pediatric therapeutics?. Ann Afr Med [serial online] 2013 [cited 2020 Aug 11];12:59-60. Available from: http://www.annalsafrmed.org/text.asp?2013/12/1/59/108259

Sir,

The increasing use of cephalosporins for empirical treatment of bacterial infections [1] that may be susceptible to penicillins has a negative effect on therapeutics and continued use of penicillins in empirical treatment without focused, periodic analysis of bacterial susceptibility may be hazardous. We carried out a retrospective review of all penicillins' sensitivity testing done on isolates from children with bacterial infections at the University of Abuja Teaching Hospital, Abuja between April 2006 and March 2010.

A total of 2,548 bacteria were isolated during the period (1320 Gram-positive, 1,228 Gram-negative). The predominant isolates were Staphylococcus aureus (35.4%), Esherichia coli (18.6%) and Streptococcus species (16.4%). Proportions of isolates are shown in [Table 1]. Sensitivity to penicillins was generally low. Overall, Gram-positive agents were more sensitive to the penicillins than Gram-negative bacteria. Of the 239 Gram-positive agents tested against penicillin G, 13 (5.3%) were sensitive. Sensitivity to penicillin G was higher with the Streptococcus species (14.3%) than with Staphylococcus aureus (3.2%). Ampicillin and amoxicillin had higher in-vitro activity against Gram-positive agents, 18.3% and 58.7%, respectively, than penicillin G. Of the 1054 Gram-positive bacteria tested against amoxicillin-clavulanate (co-amoxiclav), 779 (73.9%) were sensitive.
Table 1: Sensitivity of bacterial isolates to commonly prescribed penicillins

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The Gram-negative, on the other hand, showed much lower sensitivity to the penicillins, only 3.1% of the 160 Gram-negative tested against penicillin G was sensitive while 53.9% of the 510 Gram-negative strains tested against co-amoxiclav was sensitive. Ampicillin and amoxicillin had overall sensitivity rates of 3.2% and 31.1%, respectively. All the strains of  Escherichia More Details coli, Proteus species,  Salmonella More Details and Shigella species were resistant to penicillin G. Similarly, all the Klebsiella and Shigella species isolated were resistant to ampicillin. In contrast, about 2/3 (63.4%) of the Coliforms and Escherichia coli as well as 70.7% of Shigella were sensitive to co-amoxiclav.

Bacterial pathogens in this study were not satisfactorily susceptible to penicillins. This finding was corroborated by the report of Onalo et al.,[2] among isolates from newborn infants in Zaria which showed 94.6% of the Gram-positive agents being resistant to penicillin G, and 56% of Gram-positive and 70.8% of the Gram-negatives being resistant to amoxicillin. The low sensitivity to penicillin G may not be unconnected with its narrow bacteria coverage and its inability to resist β-lactamase. Thus, there will be no justification for employing penicillin G in empirical treatment of suspected bacterial infections. The aminopenicillins (ampicillin and amoxicillin) had better sensitivity rates, but then, sensitivity was better with amoxicillin (45.7%) than with ampicillin (9.6%). This finding is common knowledge and has led to the removal of ampicillin from the mainstream of therapeutics in some parts of Nigeria. [3] The relatively low susceptibility rates to amoxicillin among the Gram-positive (58.7%) and Gram-negative (31.1%) in the present study negates its recommendation [4] as the drug of choice in the empirical treatment of uncomplicated otitis media and other bacterial infections. In the milieu of widespread resistance, a combination of β-lactamase-stable penicillin with a β-lactam antibiotic such as ampicillin/cloxacillin or ampicillin/flucloxacillin may offer a better therapeutic outcome but then the sensitivity to cloxacillin in the present study portends a precarious situation if reliance is placed on such combinations in Nigeria. Addition of a β-lactamase inhibitor to penicillins is known to protect the drug from enzymatic hydrolysis. A study [5] has shown a 4-to 16-fold decrease in the minimum inhibitory concentration of β-lactams when combined with a β-lactamase inhibitor. This advantage should make the co-formulation of broad-spectrum β-lactams with β-lactamase inhibitors the best option for empirical treatment of bacterial infections in a community with significant levels of bacterial resistance, however, the high cost of such formulations (piperacillin/tazobactam for instance) limits their availability. Co-amoxiclav is, however, readily available and from the result of this study (Gram-positive -73.9% sensitive, Gram-negative -53.9% sensitive), co-amoxiclav could be relied upon in children with suspected Gram-positive infections before availability of the sensitivity study result. But then, the potential for clavulanate to induce the expression of chromosomal cephalosporinase may further decrease the sensitivity of erstwhile susceptible bacteria to β-lactams thereby increasing the burden of resistant pathogens in the community. [5],[6] But the combinations involving other β-lactamase inhibitors [6] such as ampicillin/sulbactam and piperacillin/tazobactam are devoid of this shortcoming and are therefore better but for the non-availability of pediatric formulations for use in community practice. Ampicillin/sulbactam co-formulation is, however, available in parenteral and enteral forms and has been adjudged to have higher clinical efficacy than co-amoxiclav. [7] In view of the aforementioned, heightened vigilance is needed when penicillins are used empirically in children with bacterial infections, while concerted efforts are required to identify the best penicillin (s) for empirical treatment.

 
   References Top

1.Robertson MB, Korman TM, Dartnell JG, Ioannides-Demos LL, Kirsa SW, Lord JA, et al. Ceftriaxone and cefotaxime use in Victorian hospitals. Med J Aust 2002;176:524-9.  Back to cited text no. 1
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2.Onalo R, Olayinka AT, Ogala WN. Emergence of multi drug resistance bacteria in neonatal infections: Implication for institutional antibiotic formularies. Nig. J paediatr 2008;35:24-30.  Back to cited text no. 2
    
3.Egri-Okwaji MT, Iroha EO, Kesah CN, Odugbemi T. Bacterial pathogens causing neonatal septicaemia in an out-born neonatal unit in Lagos, Nigeria. Qt J Hosp Med 1996;6:149-52.  Back to cited text no. 3
    
4.Jacobs MR, Bajaksouzian S, Zilles A, Lin G, Pankuch GA, Appelbaum PC. Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 oral antimicrobial agents based on pharmacodynamic parameters: 1997 U.S. Surveillance study. Antimicrob Agents Chemother 1999;43:1901-8.  Back to cited text no. 4
    
5.Qadri SM, Ueno Y, Cunha BA. Susceptibility of clinical isolates to expanded-spectrum beta-lactams alone and in the presence of beta-lactamase inhibitors. Chemotherapy 1996;42:334-42.  Back to cited text no. 5
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6.Anuradha K, Sailaja VV, Umabala P, Satheesh T, Lakshmi V. Sensitivity pattern of gram negative bacilli to three beta-lactam/beta-lactamase inhibitor combinations using the automated API system. Indian J Med Microbiol 2007;25:203-8.  Back to cited text no. 6
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7.Lode HM. Rational antibiotic therapy and the position of ampicillin/sulbactam. Int J Antimicrob Agents 2008;32:10-28.  Back to cited text no. 7
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