Presence of evidence of infection together with systemic responses like fever, hypothermia, tachycardia, etc. is described as sepsis [1]. Sepsis has alternately been called septicemia [2] or sepsis syndrome [3]. Septicemia is a common cause of pediatric morbidity and mortality [4]. World Health Organization (WHO) estimates that 85% of newborn deaths are due to infections, including sepsis, pneumonia, and tetanus [5]. Forty percent of the infants identified with sepsis die, and the biggest toll is in developing countries [5]. Considering the possible severe outcome and paucity of time, administration of empirical antimicrobial therapy is justified in patients suspected of septicemia. Appropriate empiric antibiotic therapy is associated with enhanced survival as well as a shortened hospital stay [6].

Safety and tolerability of pharmaceuticals have always been an interest and concern for those who receive and prescribe drugs. Antimicrobial agents are no exception, and with their great benefit to achieve, there must be responsibility of clinicians and consumers to understand their risks. Regardless of the antimicrobial to be used, a risk-benefit analysis should be used to weigh the risks of toxicity and antibiotic resistance against the intended therapeutic benefit. According to WHO, “an adverse drug reaction (ADR) is any response to a drug which is noxious and unintended and occurs at doses normally used in man for prophylaxis, diagnosis or therapy of disease or the modification of physiological function.” This definition excludes therapeutic failures, intentional and accidental poisoning, and drug abuse [7]. ADRs not only may result in hospital admission or prolonged hospitalization but also may lead to permanent disability or even death. Drug reactions can be classified into immunologic and nonimmunologic etiologies. The majority (75% to 80%) of ADRs are caused by predictable, nonimmunologic effects [8]. Remaining 20% to 25% of adverse drug events are caused by unpredictable effects that may or may not be immune mediated [8]. Predictable ADRs may either be avoidable or tolerated, implying such events as toxicity, drug interactions, and secondary effects. Unpredictable and usually unavoidable ADRs include idiosyncratic or allergic reactions as well as intolerance.

Monitoring and documentation of ADRs including preventable and nonpreventable ADRs are crucial to encourage and to ensure safe use of pharmacologic agents. For assessing ADRs, other causes for the adverse drug events should be excluded; a temporal relationship between drug use and onset of the event should exist; improvement should be noted following drug cessation, reactivation upon rechallenge of the drug should be noted; and the reaction is known to be associated with the drug in question. The exact incidence of specific adverse events is often impossible to assess, although clues are gathered from multiple sources. Awareness of the risk groups may decrease the incidence of preventable and serous antimicrobial related adverse effects as well as the extra cost incurred due to these untoward effects. Previously we have showed the antimicrobial therapy and outcome of septicemia patients [9]; therefore, the current study was conducted to monitor the incidence and assess severity of ADRs during the antimicrobial therapy of septicemia patients admitted at a university hospital.

The present study illustrates the magnitude of the problem of ADRs in selected hospitalized patients of septicemia with detection of ADRs in 26.5% of the study population. This report is higher than the findings of as other study [13] and comparable to a joint study report of United States and Canada where the incidences ranged from 15% to 27% [14]. Differences in methodology for data collection (e.g., spontaneous reporting versus chart review) may explain the variability in reported frequencies.

In the present study, higher numbers of ADRs were observed in female patients as compared to male patients (Table 1). Hence, females developed ADRs 3.6 times more often than males. It might be attributed that the females being more sensitive to the effect of drugs than the males [15-17]. Incidence of ADR was 1.6 times higher in patients, who were aged more than 60 years of age (Table 4). Subsequently incidence of ADR was two times higher in patients with more than two comorbid conditions. It has been observed that there is correlation between number of ADRs and the number of comorbid conditions in the patients.

A case of generalized tonic clonic seizure associated with amoxicillin-clavulanic acid (Augmentin, GlaxoSmith-Kline, London, UK; on dose 250:50 mg frequency four times daily route of administration intramuscular administration) was observed in the present study. This might be linked to β-lactam antibiotics in which β-lactam ring is present, which directly or indirectly can stimulate central nervous system. Blood in stool, 1/15 (6.7%) reactions associated with amoxicillin-clavulanic acid was observed. A study from Italy reported 2% hematological reactions associated with amoxicillin-clavulanic acid [18]. It may be linked due to thrombocytopenia and prolongation of prothrombin time, which are described as the uncommon side effects in the summary of product characteristics of amoxicillin-clavulanic acid [19]. However, we found little information about hematological reactions related to amoxicillin-clavulanic acid.

The higher incidence of ceftriaxone-tazobactam-induced diarrhoea could be explained by its greater resistance to β-lactamases, which might result in a higher concentration of ceftriaxone in the intestine and a consequent stronger modification of the bacterial flora, responsible for diarrhoea. Although these effects are usually minor and transient, they may lead to the interruption of treatment; therefore, further studies are necessary to assess the role of ceftriaxone in gastrointestinal disturbances.

Ofloxacin induced itching and purpural rashes were observed in one patient out of five prescription drug (20%). Liang et al. [20] reported 2% of skin rash as an ADR due to ofloxacin in a comparative study of ofloxacin versus co-trimoxazole for prevention of infection in neutropenic patients. Gemifloxacin induced skin rash was detected in one patient out of two prescriptions, 50% patients. It also caused diarrhea in one patient out of two prescriptions. A study reported appearance of rash more common with use of gemifloxacin, particularly in younger women (39 years old) treated for 7 days (12%) versus those treated for only 5 days (2.1%) [21]. Another study reported lower incidence of rash in the 5-day cohort (0.4%) versus the 7-day cohort (2.8%), overall in 1.6% of patients [22]. They also reported 3.1% of diarrhea as the adverse events of gemifloxacin [22]. Quinolones are associated with a nonspecific capacity to cause mast cells and basophils to release histamine, on the basis of animal studies measuring plasma histamine levels and the appearance of a generalized rash [23]. This may be, at least in part, a potential mechanism for some immune-mediated adverse reactions such as rash.

All the detected ADRs were evaluated according to Naranjo’s algorithm probability scale; most of the ADRs were categorized as probable and as definite in only one patient. Majority of the ADRs were preventable in nature. In this study, we did not asses the types of ADRs. On severity scale, majority of these ADRs were moderate, followed by mild and in one patient the reaction was severe which appeared on the fixed dose combination therapy of amoxicillin-clavulanic acid (Augmentin) at the dose of 250:50 mg, four times daily frequency and on intramuscular administration. The most common organ systems affected with ADRs in our study were gastrointestinal and skin. This is supported by previous studies which reported gastrointestinal ADRs among the top three ADRs [17].

Antimicrobials have played important role in the treatment and cure of diseases; however, irrational prescribing, different types of races availability, variation in climatic conditions in Indian region may lead to differing types of ADRs in Indian population and these ADRs not only may result in hospital admission or prolonged hospitalization, increase economic burden but also may lead to permanent disability or even death. Awareness of the risk groups may decrease the cost as well as the incidence of preventable and serous antimicrobial related adverse effects. The most common antimicrobials involved in ADRs were newer one such as teicoplanin and gemifloxacin, although the numbers of prescription of these antimicrobials were one and two, respectively. As expected patients with more than two co-morbid conditions experienced higher percentage of ADRs. These findings need to be verified in larger number prescriptions containing these antimicrobials.