Irrational prescribing practices exist all over the world and eventually they lead to unwanted effects in patients (Akl et al. 2014). In this study, WHO/INRUD prescribing indicators were used to determine current prescribing practices and antibiotic use patterns in a tertiary care hospital in Pakistan. The findings from this study are important to the health system of Pakistan because they help to assess whether the BVH is following a set norm of practices to ensure optimal medication use. Only a limited number of studies are available from Pakistan on this topic and therefore our findings provide a source of baseline information for continuous monitoring of drug therapy and process improvement at the institutional level. A & E departments are often the first point of contact with the healthcare system and in Pakistan there is a considerable throughput of patients in these departments. Turnover of patients in this setting is higher than general wards and one should not underestimate the importance of the appropriate prescribing of antibiotics to ensure current levels of resistance do not continue to climb. In addition to the contribution made in the Pakistani context, our findings may also be relevant to other countries with similar drug use practices or with similar health care systems. This study may provide the impetus for academics, clinicians and hospital administrators in those countries to begin to assess the status of their own nations prescribing within A & E departments; especially as it relates to antibiotics.
Prescribing indicators
The contents of a prescription are influenced by a prescribers’ training, their attitude towards the disease being treated and the type of healthcare system within which they work. The results of the current study revealed that the average number of drugs per prescription were 2.3 (SD = 1.3) (Table 1). This value is higher than the admissible range of 1.6–1.8 drugs per encounter. In contrast to our findings, the average number of drugs prescribed was lower in Malawi (1.8) (Gelders and World Health Organization 1992) and Zimbabwe (1.3) (Hogerzeil et al. 1993). However, the studies conducted in Afghanistan (3.9) (Ahmad et al. 1995) and India (5.6) (Akhtar et al. 2012) reported a relatively higher number of drugs per prescription which could be attributed to multiple reasons. Incompetency on the part of physicians, absence of evidence-based guidelines, incentives to the prescribers, lack of continuous medical education of the prescribers and the shortage of therapeutically correct drugs provide a few reasons. Having a higher number of drugs per prescription can adversely influence treatment outcomes as patients are more likely to be non-compliant and are at greater risk of interactions and adverse events. Moreover, prescribed medicines that are not warranted lead to fiscal implications for national healthcare systems including budget blowouts (Atif et al. 2016b).
Well-founded recommendations by the WHO regarding generic prescribing provide a safety measure for patients (Atif et al. 2016a). These recommendations clearly describe what should happen and they provide accessible information and promote effective communication among healthcare providers (Akl et al. 2014). This study demonstrates that generic prescribing was at a level of 83.1% (optimal value being 100%) (Table 1). In a number of countries generic prescribing is much lower; as in Andorra (6%) (Vallano et al. 2004) and Ecuador (37%) (Hogerzeil et al. 1993) whilst higher levels have also been reported in Timor-Leste (92%) (Stanley Chindove and Martins 2012) and Ethiopia (98.7%) (Desalegn 2013).
Our results revealed that antibiotics were prescribed on over half the prescriptions (52.2%) (optimal value 20.0–26.8%) (Table 1). This would suggest that either every second person who presents at the A & E department has an infection related issue, or that there is excessive and inappropriate prescribing of antibiotics occurring in this hospital department. To compare internationally, this value was relatively lower in other developing countries such as Bangladesh (25%) (Guyon et al. 1994) and Brazil (28.8%) (Holloway and Henry 2014). In a few countries, antibiotic prescribing was higher such as in Kenya (73.4%) (Holloway and Henry 2014), Timor-Leste (70%) (Stanley Chindove and Martins 2012), and Sudan (70.4%) (Holloway and Henry 2014). Unnecessary prescribing of antibiotics is a worldwide problem that eventually leads to ADRs and frequent hospital admissions (Beringer et al. 1998).
In our study, 98% of prescriptions included at least one injectable product (optimal value 13.4–24.1%) (Table 1). This value was much higher than the studies conducted in Afghanistan (17%) (Ahmad et al. 1995) and Kuwait (9.1%) (Awad and Al-Saffar 2010). We conducted this study in the A & E department where the excessive use of injectables may be attributed to the patients’ condition such as emergency and unconscious cases where the oral route for drug administration is often not possible. Nevertheless, excessive use of injections may lead to a higher probability of blood borne diseases (World Health Organization 2002) and injections are always more expensive than the equivalent oral formulation (Akl et al. 2014).
With regard to drugs prescribed from the EDL, our findings were comparable to other studies conducted in the Lao People’s Republic (86.2%) (Holloway and Henry 2014) and Bangladesh (85%) (Guyon et al. 1994). Rational prescribing includes the optimal use of drugs selected from the EDL which are issued by the WHO. These agents are older, time tested and available at lower cost than the originator branded drugs (Akl et al. 2014).
Antibiotic usage patterns
There is some evidence to support the notion that antibiotic consumption is much higher in developing countries as compared to developed countries (Knobler et al. 2003; Center for Disease Dynamics Economics & Policy 2015). According to one study, 35–60% of the patients were prescribed antibiotics and less than 20% of antibiotics were prescribed appropriately (World Health Organization 2001a, b).
In this study, out of the 52.4% (n = 2262) prescriptions containing antibiotics, 77.7% (n = 1758) contained one antibiotic, 22.1% (n = 499) included two antibiotics and 0.2% (n = 5) had three antibiotics. These findings can be compared with a study conducted in Jordan (Al-Niemat et al. 2014), which showed that out of 85% prescriptions with antibiotics, 88% prescriptions had one antibiotic, 11% had two and 1% had three antibiotics. Likewise in a Turkish study involving 39.4% prescriptions with antibiotics, 73.6% prescriptions had one antibiotic, 19.6% had two, 5.7% had three and 1.1% had four antibiotics (Erbay et al. 2003). Similarly, results of a study conducted in Nepal revealed that 21% prescriptions included one antibiotic, 37% prescriptions included two, 28% prescriptions included three, 10% included four and 4% of the prescriptions included five and above antibiotics (Palikhe 2008).
Our study demonstrated that the most frequently prescribed classes of antibiotics were cephalosporins (81.5%), penicillins (6.4%) and fluoroquinolones (6.2%) (Table 2). A study performed in Saudi Arabia revealed that cephalosporins (31.9%), penicillins (24.9%) and macrolides (9.7%) were the most frequently prescribed classes of antibiotics (Mohajer et al. 2011). In a similar manner, a study from Turkey reported that cephalosporins (19.9%) were the most commonly prescribed class followed by penicillins (19.1%), aminoglycosides (11.7%) and quinolones (11.1%) (Erbay et al. 2003). Another study showed that cephalosporins were the most frequently prescribed antibiotics (34%) followed by penicillins (33%), aminoglycosides (16%) and fluoroquinolones (6%) (Palikhe 2008). A study from Jordan revealed that penicillins (46%) and macrolides (39%) were the most frequently prescribed antibiotic classes (Al-Niemat et al. 2014). With regard to individual antibiotics, the findings of our study revealed that ceftriaxone (71.8%) contributed the highest percentage share amongst all the antibiotics followed by cefotaxime (5.6%), metronidazole (4.7%), amoxicillin (4.7%), ciprofloxacin (4.2%) and moxifloxacin (1.9%). An Indian study showed that the highest prescribed antibiotics were cefixime (37.98%), ceftriaxone (7.97%), azithromycin (6.33%) and gentamicin (6.25%) (Khan et al. 2011). In another study, azithromycin contributed the highest percentage share (97%) of the total antibiotics (Al-Niemat et al. 2014). It is clear from this body of literature that the extent of antibiotic prescription is high but that there is considerable variation in the number and types of antibiotics selected to prescribe. What is concerning from our study is the selection of very high powered cephalosporins first line. This study provides the platform to implement policy that should result in a change in this prescribing behavior. In this regard the study is very relevant and has implications for policy and practice that can make a difference in Pakistan.
The increasingly growing threat of AMR and the lack of a significant pipeline of new antibiotics in development has drawn attention toward multi-drug therapies (Golan et al. 2011). In the majority of cases infections are usually cleared within a few days of antibiotic treatment with a single agent, but severe and complicated infection may require longer treatment with a combination of multiple antibiotics (Nicolle and Committee 2005). We found that the most commonly prescribed antibiotic combinations were ciprofloxacin with metronidazole (52.1%) and ceftriaxone with metronidazole (38.8%). In the field of medicine, the multi-drug antibiotic therapies are usually sought to achieve broader antibacterial spectrum (Ejim et al. 2011). Different occasions where these combination therapies have been shown to be more effective include; synergism; prevention of AMR; and as empirical therapy for poly-microbial infections. The most commonly anticipated drug–drug interactions with antibiotic combinations are antagonism, addition and synergism (Rybak and McGrath 1996). In most cases, synergistic effects are considered for treatment failure cases or when the incidence of AMR development is most likely (Cremieux and Carbon 1992). But some recent studies have reported that antimicrobial synergistic combinations may speed up the process of AMR development (Pena-Miller et al. 2013).
There are certain other risks and adverse effects associated with the use of antibiotics and antimicrobial combinations. The major associated risks include development of super-infections, augmented toxicity and greater cost. The well described adverse effects include hypersensitivity reactions, diarrhea, nephrotoxicity and coagulopathy (Rybak and McGrath 1996). Published studies have emphasized the rational use of antibiotics (alone or in combination) to prevent the AMR development (McGowan 1983), improve quality of patient care (Shao-Kang et al. 1998) and to minimize the cost of therapy (Segade 2000).