|Year : 2016 | Volume
| Issue : 1 | Page : 23-29
Clinical, serological, microbiological, and outcome study of 200 cases of short duration fever without prior exposure to antibiotic
Prasanna K Satpathy1, Mukund Sudhakar Wasekar1, Pradnya M Diggikar1, RN Misra2, Amar Patil1, Priyanka Zagde1
1 Department of Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
2 Department of Microbiology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
|Date of Web Publication||22-Dec-2015|
Mukund Sudhakar Wasekar
Department of Medicine, Dr. D. Y. Patil Medical College, Pimpri, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Background : Short duration fever is a very common presenting symptom of infections which are mostly self-limiting and do not require any antibiotics. Most of these patients presenting to primary care centers are exhibited antibiotics irrationally without any investigation results. Antibiotics are not a panacea for all fevers. This title was chosen to discourage the usual practice of indiscriminate use of antibiotics in short duration self-limiting fevers, increasing emergence of antibiotic resistance bacteria. This study was conceived and designed after The Lancet in 2010 reported the emergence of resistant New Delhi strain of metallo-beta-lactamase 1 Gram-negative Enterobacteriaceae from India, Pakistan, and the UK due to irrational use of antibiotics. Moreover, there are very scanty literature reports on "Short duration Fevers." This study is likely to advocate rational scientific approach to the management of short duration fever. Objectives: This study was conducted to (a) arrive at a definite diagnosis and formulate various etiologies of short duration fever in this tertiary care hospital, (b) rational use of specific antibodies when indicated, and (c) study the outcome of therapy. Materials and Methods: This was an observational cross-sectional study comprising 200 fresh consecutive inpatients of fever of <2 weeks duration who has not been exposed to any antibiotic prior to hospitalization between July 2012 and September 2014. They were subjected to clinical, microbiological, and serological studies and other specific studies when indicated. Results: Common etiology for fever was found to be nonspecific viral fever (45%), which did not need antibiotics, then dengue fever (26.5%), enteric fever (7%), and malaria with Plasmodium vivax (4%) predominance. Conclusion: Clinicians needs to restrict to indiscriminate use of antibiotics in any febrile patients to prevent the emergence of antibiotic resistance. More number of similar studies need to be carried out globally to create awareness among clinician regarding the cautious and rational use of antibiotic therapy in short febrile patients.
Keywords: Antibiotics, fever, short duration
|How to cite this article:|
Satpathy PK, Wasekar MS, Diggikar PM, Misra R N, Patil A, Zagde P. Clinical, serological, microbiological, and outcome study of 200 cases of short duration fever without prior exposure to antibiotic. Med J DY Patil Univ 2016;9:23-9
|How to cite this URL:|
Satpathy PK, Wasekar MS, Diggikar PM, Misra R N, Patil A, Zagde P. Clinical, serological, microbiological, and outcome study of 200 cases of short duration fever without prior exposure to antibiotic. Med J DY Patil Univ [serial online] 2016 [cited 2017 Aug 20];9:23-9. Available from: http://www.mjdrdypu.org/text.asp?2016/9/1/23/172421
| Introduction|| |
Fever is a pervasive and ubiquitous theme in human myth, art, and science. Fever is such a common manifestation of illness that is not surprising to find an accurate description of the febrile patients in early-recorded history. 
Fever is one of the most common and worrisome symptoms that health care providers must assess. An understanding of what defines an abnormal temperature, the pathophysiology of temperature regulation, the beneficial and harmful effects of fever, and its treatment are vital to the care of the febrile patient.
Fever is an elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set-point.  This increase in set-point triggers increased muscle tone and shivering.
Normal body temperature displays a diurnal variation with lower values in the early morning hours and higher values in the afternoon. Normal oral temperature 36.5-37.5°C varies from rectal temperatures is generally 0.4°C (0.7°F) higher than oral reading. Lower esophageal temperatures reflect core temperature. 
There is a long list of causes of short duration fever. These are respiratory tract infection, urinary tract infection, meningitis, pyogenic infections, malaria, typhoid fever, viral fever, dengue, leptospirosis, chikungunya, etc.
| Materials and Methods|| |
It was an observational study comprising 200 fresh consecutive cases of fever of <2 weeks duration admitted to the Tertiary Care Teaching Hospital between July 2012 and September 2014 with exclusion criteria - age <15 years, duration >2 weeks, fever with established etiologies like HIV, malignancy, patients on steroids therapy, renal failure, patients on anticancer drug therapy, and patient prone to develop secondary infections like tuberculosis, brucellosis, perioperative cases, postpartum cases, fever associated with boils, carbuncles, and other skin infection, those who are already exposed to antimicrobial therapy for the febrile illness, healthcare associated fever like ventilator associated, catheter-induced or drug fever, or device-induced fever.
Two 20 ml of blood sample were collected from two separate sites at 1 h interval observing aseptic precaution. This was inoculated into bactek specific blood culture bottle and immediately sent for culture. Blood sample were also collected for immunological studies like rapid malaria, dengue, Leptospira, viral hepatitis, chikungunya, Brucella, blood smears taken for malaria parasite, urine sent for examination, and culture.
Investigation results were correlated with clinical probabilities. Statistical analysis was done using frequencies and percentages with Epi Info 7 statistical software developed by Centre for Disease Control, Atlanta, Georgia, USA. This study was carried out after the Institution Ethical Committee clearance.
| Results|| |
Out of 200 patients, 183 were male and 17 were females. The highest number of cases were found in the age group of 21-30 years followed by age group of 15-20.
Almost 50% had high-grade intermittent fever followed by intermittent low-grade fever [Figure 1].
|Figure 1: Bar diagram showing type of fever with distribution of cases in study group|
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Most of the patients came with a fever of <7 days of duration (79.5%). Most common presenting symptoms were chills (84%), headache (43%), body ache (41%), followed by cough (18%), and bone pain (15.5%) [Figure 2].
|Figure 2: Bar diagram showing symptoms wise distribution of cases in study group|
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Pallor was found in 35 cases (17.5%), icterus in 2 (1%), lymphadenopathy in 3 (1.5%) upper respiratory tract infection (URTI) was found in 8 patients, hepatomegaly in 6, and splenomegaly in 6 patients.
Most common diagnosis based on clinical findings was viral fever (47.5%), followed by dengue fever (25.5%), and enteric fever (8.5%) [Figure 3].
|Figure 3: Bar diagram showing clinical diagnosis wise distribution of cases in study group|
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Patients with total leukocyte count more than 10,000 were 26 (13%), erythrocyte sedimentation rate more than 10 were 103 (51.5%), and patients with thrombocytopenia (platelets <1 lakh) were 44 (22%).
Out of 200 patients, 9 were positive for malaria most common being Plasmodium vivax malaria (3.5%) followed by Plasmodium falciparum malaria (1%) [Table 1].
Fifty-three were positive for dengue, 29 (14.5%) positive for dengue NS1 antigen, 7 (3.5%) for immunoglobulin G (IgG), 8 (4%) for IgM, followed by mixed type-positive for more than one type (4.5%) [Figure 4].
|Figure 4: Bar diagram showing type of dengue wise distribution of cases in study group|
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Fourteen cases were positive for Widal (7%). In our study, only one case was positive for Leptospira IgM antibody.
Most common isolate in blood culture was Staphylococcus aureus in 6 cases (3%) 6. The second common isolate was Acinetobacter species in 3 cases (1.5%), followed by Klebsiella pneumoniae-1 and Salmonella Paratyphi-1 [Table 2]. Out of 6 isolate of S. aureus, 3 were methicillin-resistant S. aureus (MRSA) and 3 were methicillin sensitive S. aureus (MSSA). Above organisms were non-extended-spectrum ß-lactamases (ESBL) producer and were sensitive to quinolones, cephalosporins, and carbapenems.
|Table 2: Sensitivity pattern of blood culture isolates other than Staphylococcus aureus|
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Blood culture was sterile in 94% cases [Figure 5].
|Figure 5: Pie diagram showing blood culture isolate wise distribution of cases in study group|
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Positive urine culture was detected in 3 cases. Escherichia coli was found in 2 cases (1%) and S. aureus in 1 case (0.5%) both non-ESBL. Two cases were positive for sputum culture in which Acinetobacter species was found in 1 case, and K. pneumoniae was found in 1 case, both were non-ESBL [Table 3].
|Table 3: Sensitivity pattern of sputum culture isolate wise distribution of cases in study group|
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In urine analysis, pus cells were present in 15 cases (7.5%). One case was positive for both blood culture and urine culture. Acinetobacter species in blood and E. coli in urine [Figure 6], [Figure 7] and [Table 4].
Chest X-ray was showing pleural effusion in 2 cases, pneumonitis in 2, consolidation in 2, and chronic obstructive pulmonary disease in 2 cases. Most common ultrasonography findings was hepatomegaly in 8 cases, followed by splenomegaly in 5 cases, and hepatosplenomegaly in 3 cases [Figure 8].
|Figure 8: Chest radiograph showing right upper lobe consolidation. In this patient, Acinetobacter species was isolated in the sputum culture|
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Most of the patients were discharged within the period of 7 days (93.5%). Patients were afebrile at the time of discharge. Forty-seven patients were treated by antibiotics after microbiological and/or serological investigations. Nineteen patients were started on antibiotics based on hard clinical evidence [Table 5] as per the antibiotic policy of the hospital pending antibiotic sensitivity test (AST) of infected specimens.
|Table 5: Initiation of antibiotic therapy on hard clinical evidence as per hospital antibiotic policy|
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In our study, out of 200 patients 90 were diagnosed as nonspecific viral fever, 53 were diagnosed as dengue fever, 14 were enteric fever, and 11 were urinary tract infection [Table 6].
95 patients were given a diagnosis as viral fever based on clinical findings out of which 77 were came positive as nonspecific viral fever (accuracy - 81.05%). Fifty-one patients were considered as dengue fever on clinical findings out of which 40 were came positive as dengue fever (accuracy-78.43%) [Table 7].
|Table 7: Correlation between clinical and fi nal diagnosis in study group|
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Out of 200 cases, 199 were cured and 1 case died due to K. Pneumoniae causing multiorgan failure.
| Discussion|| |
In this study, 200 patients presenting with fever of <14 days of duration were studied. Based on the clinical findings their serological and/or microbiological specimens were taken to arrive at a final diagnosis.
In our study, out of 200 patients 183 were males and 17 were females, and the maximum number of patients were in the age group of 21-30 years. These findings are consistent with the findings of Goyal et al.  Male predominance in febrile illness as compared to females may be due to the fact that proper covering of body and maximum indoor stay in females supported by Guha-Sapir and Schimmer. 
Out of 200 patients, 159 were presented with fever of <7 days of duration and the most common type of fever being high-grade and intermittent. The most common symptom was chills (45%) followed by headache and body ache. Another common symptoms were dry cough, bone pain, and vomiting. Signs like pallor was found in 35 cases, mostly associated with malaria.
On the basis of clinical findings, 95 patients were given the diagnosis of viral fever, followed by 51 patients were dengue fever, and 17 were enteric fever. Malaria was suspected in 7 patients. In our study, 1 patient was having the signs of meningitis which on doing cerebrospinal fluid analysis came out to be pyogenic meningitis. Leukocytosis was present in 26 cases and 44 cases platelets count between 20,000 and 1 lakh, but none of them had bleeding manifestation.
Out of 200 cases, 9 were positive for malaria and predominance of P. vivax (7 out of 9 cases) compared with Plasmodium falciparum was reported. Abrahamsen et al.  Vellore India supports the above finding. Another study done at Kolkata, Pal et al. . showed the predominance of P. vivax malaria in which 200 cases of short duration fever were studied and 22 came as P. vivax and 9 were Plasmodium falciparum malaria. Malaria imposes a major global health burden in large part because the Plasmodium parasite readily evolves drug resistance and require more expensive artemisinin-based combination therapy. 
In our study, 53 patients were positive for dengue fever out of which 29 were dengue NS1 and 8 were dengue IgM, and 9 were mixed. Most common age group affected was 21-30 years with male predominance. The study done by Gupta et al.  and Chakravarti and Kumaria  supports the above findings. Gallbladder sludge could be found in some dengue fever patients. In our observation, the findings of gallbladder sludge were demonstrated in 3 of 53 abdominal sonographic examinations of dengue patients and pleural effusion (3/53) were noted too. Chi-Hung Lo et al.  support the above findings.
Dengue is emerging as a major public health problem in India. India witnessed widespread dengue fever outbreak in the year 2012. Tamil Nadu reported the highest number of cases in the country being 9249, followed by West Bengal, which reported 6067 cases. The other states which also reported increased number of dengue cases were Maharashtra, Kerala, Karnataka, Odisha, Delhi, Gujarat, Puducherry, Haryana, and Punjab.
Fourteen cases were positive for enteric fever, and 1 case was positive for Leptospira. None of them were positive for Brucella.
All the patients in our study were subjected to blood culture and before the initiation of antimicrobials. Out of them, 11 were having positive blood culture. S. aureus was isolated in 6 cases, followed by Acinetobacter species in 3 cases, Salmonella Paratyphi in 1 case, and K. pneumoniae in 1 case.
S. aureus is a versatile and virulent pathogen in humans, who serve as natural reservoirs for this pathogen. The rates of infections caused by staphylococci, both community- and hospital-acquired strains, are increasing steadily. Concurrently, treatment of these infections is becoming more difficult because of the increasing prevalence of multidrug-resistant strains.  Out of 6, S. aureus cases 3 were MRSA and 3 were MSSA. Patients were treated according to their culture sensitivity results.
Urinary tract infections (UTIs) are the second most common type of infection in the body; hence, one of the common cause of fever. We found 11 cases UTI out of 200. Dysuria was the common symptom. In urine analysis, pus cells were present in 15 cases and urine culture was positive in 3 cases in which E. coli was isolated in 2 cases and S. aureus was isolated in 1 case. Hooton, M.D.  supports the above finding in which E. coli was a common pathogen and was a major cause for fever and dysuria.
Patients having a clinical diagnosis of lower respiratory tract infection were subjected to sputum culture in a suitable container. Five patients were given the diagnosis of LRTI. Out of 5 patients, 2 were showing a classical picture of right upper lobe consolidation in their X-ray film. Acinetobacter species was isolated in 1 case and K. pneumoniae in 1 case. Both these organisms were non-ESBL producers. They were treated according to their sputum culture sensitivity report.
Acinetobacter is an aerobic Gram-negative coccobacillus known to cause nosocomial pneumonia. In our study, we had a young male with community-acquired pneumonia with Acinetobacter, an uncommon cause of community-acquired pneumonia. He presented with a high-grade fever with chills and constricting type of retrosternal chest pain. His sputum culture showed non-ESBL Acinetobacter species. His chest X-ray showed right upper lobe consolidation and electrocardiogram was suggestive of acute inferolateral wall myocardial infarction. The patient was started on antibiotics as per the antibiotic stewardship guidelines of this hospital and thrombolytic therapy and then shifted to antibiotics according to his sensitivity report. This is a rare combination of pneumonia with acute myocardial infarction.
187 cases out of 200 were discharged within 7 days of hospitalization, and they were afebrile. Duration of fever is relatively short in acute infection diseases compared to chronic infections and other diseases. The most common laboratory abnormality was an elevated erythrocyte sedimentation rate (51.5%) and leukocytosis (13%). These findings are similar to the findings of Fukuhara et al. 
Any patient coming with fever should be covered with antibiotics is a very irrational practice. In this series, we have used antibiotics rationally based on isolation of organism with antibiotic sensitivity and on hard clinical grounds like meningitis, pneumonia pending the culture sensitivity report. 47 of 200 patients were started on antimicrobial therapy as per the microbial and/or serological investigations, 19 were started on hard clinical evidence like meningitis, URTI, lower respiratory tract infection, and urinary tract infection. It is important that irrational antibiotic exposure "doot" to "hospital" and at "hospital entrance" must be avoided in order to minimize the emergence of antibiotic resistance. It has been shown that inadequate therapy for infections in critically ill, hospitalized patients is associated with poor outcomes, including greater morbidity and mortality, as well as increased length of stay, Ibrahim et al.,  and Kollef et al. 
In our study, the correlation between clinical and final diagnosis was studied in terms of accuracy. Ninety-five patients were diagnosed clinically as viral fever out of which 77 were come positive with 81.05% of accuracy.
In our study, the mortality rate was 0.5%, only one patient died due to severe community-acquired pneumonia due to K. pneumoniae (Friedlanders bacillus) isolated both from blood and sputum leading to septicemia and multiorgan failure.
| Conclusion|| |
In this observational study, we found a male predominance and the maximum number of patients were in the age group between 21 and 30 years.
A majority of patients presented with high-grade fever with common symptoms of chills, body ache, and headache.
A thorough clinical examination and history in more than half of the cases was able to lead to a good diagnosis which was subsequently correlated with microbiological and/or serological study.
Patients were subjected to suitable microbiological specimens. Common organism isolated in blood culture was S. aureus with an equal number of MRSA and MSSA reflecting the leading cause of bacteremia followed by Acinetobacter species. In urine culture, E. coli was common and in sputum culture, K. pneumoniae and Acinetobacter species were isolated as severe community-acquired pneumonia. They were treated according to their AST. Acquiring MRSA, Acinetobacter, and Klebsiella in the community may be due to widespread use of antibiotics in the community at large scale. 
Common etiology for fever was found to be nonspecific viral fever, which did not require antibiotics.
Clinicians need to restrict to indiscriminate use of antibiotics in any febrile patients to prevent the emergence of antibiotic resistance like MRSA, ESBL, and metallo-beta-lactamase which has been reported to be on the rise globally including India. 
More number of similar studies need to be carried out globally to create awareness among clinician regarding the cautious and rational use of antibiotic therapy in short febrile patients. Community study is recommended to find out the burden of asymptomatic carriers of ESBL in the community.
To a physician "Fever" is a Pandora's box as "pain abdomen" to a surgeon. The antibiotic is not a panacea for all febrile patients, and the goal should be "when not to use Antibiotic" like when not to open abdomen. This must be ingrained deep into minds of undergraduate and postgraduate students in medical curricula.
The learning module recommended in the management of short duration fever is:
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- Short duration fever cases, without any clinical signs of bacterial infection or hemodynamic compromise, should be managed by paracetamol (acetaminophen), and other symptomatic therapy while awaiting for investigation of short duration fever (dengue, malaria, Leptospira, chikungunya, blood culture, and leukocytosis).
- Cases with clinical signs of bacterial infection should be treated with antibiotic stewardship of that hospital, to be changed after receiving the antibiotic sensitivity report.
- No case should be exhibited antibiotic just to prevent the emergence of secondary bacterial infection like in viral fever.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]