EPIDEMIOLOGY, BACTERIAL PROFILE, AND ANTIBIOTIC SENSITIVITY OF LOWER RESPIRATORY TRACT INFECTIONS IN SANA’A AND DHAMAR CITY, YEMEN 

Abdulrahman Y. Al-Haifi¹, Abdul Salam Mohamed Al Makdad², Mohammed Kassim Salah², Hassan A. Al-Shamahy^2*, Wadee Abdullah Abdulwahid Al Shehari³

¹Department of Microbiology, Faculty of Medicine , Dhamar University, Dhamar, Yemen

²Department of of Medicine, Faculty of Medicine, Dhamar University, Dhamar, Yemen

³Medical Microbiology and Clinical Immunology Department, Faculty of Medicine and Health Sciences, Sana’a University, Republic of Yemen

Objectives:  Lower respiratory infections (LRTIs) are the leading reason of death infectious diseases in the world and the fifth leading cause of death in general. The study aimed to identify the general characteristics of LRTI, the causative bacteria and the results of sensitivity to antibiotics.

Subjects and methods:  A multicentre prospective study was performed at 3 University hospitals. The study included 555 clinical diagnostic cases as LRTI cases, 328 male and 227 female, aged 3 to 69 years. Clinical and demographic data were collected in the standard questionnaire, and samples included sputum or bronchial lavage (BAL) staining and culture. Samples were cultured in 3 different bacterial media, blood agar and LJ slope, chocolate agar with Co₂; cultures were then examined for possible bacterial pathogens of LRTI. Possible bacterial pathogens were isolated and identified by standard laboratory techniques, and microbial sensitivity testing was carried out by disc diffusion method.

Results:  LRTI was recorded among all age groups and with less frequency in children less than 16 years of age. A large number of LRTI (36.2%) was not diagnosed, most in CAP (52.4%), followed by HAP (33.9%) while unidentified cases were lower in AECOPD (22.8%). CAP isolates are K. pneumoniae (26.2%), S. pyogens (12.3%), and S. pneumoniae (9%); in HAP are MSSA (24%), E. Coli (12.9%), MRAS (11.1%), K. pneumoniae (10.5%) and P. aeruginosa (7%); and in AECOPD are M. catarrhalis (47.2%), K. pneumoniae (17.2%), H. influnzae (10.7%) and P. aeruginosa (2%). In Gram-positive bacteria, high resistance to ampicillin/sulbactam (100%) and amoxicillin/clavulanate (100%) was recorded, while moderate resistance to amikacin, vancomycin, cefepime and moxifloxacin was recorded. In Gram-negative bacteria, a high resistance to 3^rd g Cephalosporin’s  (68.5%) was recorded, while a moderate sensitivity to the other antibiotics tested was recorded.

Conclusion:  There is a high rate of undiagnosed LRTI in Yemen and this highlights the need for health authorities to develop strategies to diagnose most of the causes of LRTI, including Mycoplasma, Chlamydia, and viral causes. No antibiotics are completely effective in treating LRTI in our area and antibiotic sensitivity should be performed in all cases.

Keywords: Antibiotics, Dhamar city, Lower Respiratory Tract Infections (LRTIs), Sana’a City, Yemen. 

INTRODUCTION

Lower respiratory tract infection (LRTIs) is the leading cause of infectious diseases of death worldwide, the fifth on the whole cause of death, and the second general reason of disability adjusted life years (DALYs), although they are largely preventable causes of diseases and Death¹. There have been alterations in the epidemiology of LRTIs in the previous ten years as there has been a reduction in the number of cases among children under 5 and an increase in infection among older adults as well as an increase in viral infections¹. Nevertheless, there is no standardized classification of "LRTIs", a fact which has been said to impede the admiration of its true epidemiological importance^2,3. From an epidemiological standpoint, most definitions of LRTI include influenza, pneumonia, bronchitis (including acute exacerbations of chronic obstructive pulmonary disease [COPD] [AECOPD]) and bronchiolitis as important diseases^1-3.  The three most important bacterial respiratory pathogens are Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Unfortunately, these causes are spreading and increasing the rate of their resistance to antibiotics worldwide^4,5,6. The consequence of monitoring the development of this resistance has led to many national, regional and international monitoring programs. Nevertheless, the results of surveillance studies show wide differences in sensitivity rates, both geographically and over time^7,8. Bacterial resistance patterns for antibiotics may differ from one region to another depending on the pressure on the antibiotics in that region⁹. Consequently, there is a great need for local resistance spread data in order to guide the experimental prescription and identify areas where new antibiotics with greater effect are needed.  In Yemen, data on epidemiology of LRTIs and antibiotic patterns are still rare for bacterial causes. Over the past four years, an increase in mortality has been observed among residents of the capital, Sana’a, due to LRTIs¹⁰. Hence, the current study was planned to isolate the bacterial profile of LRTIs in Yemen and to verify the antibiotic susceptibility among these pathogens in our areas.

SUBJECTS AND METHODS

The selected cases were defined as all patients who had a major complaint of LRTIs and entered the selected Hospitals. The technique of sampling in the study was case finding. As for determining the size of the sample, it was relied on taking all patients who attended selected hospitals during the study period. This study was conducted on 555 hospitalized patients with LRTI in university hospitals in the cities of Sana’a and Dhamar during the period from October 2015 to October 2018. All patients were subjected to full clinical, radiological and relevant laboratory examinations.Clinical sample analyzes were performed in the laboratories of the National Center of Public Health laboratories Sana’a (NCPHL)). The study included 187 patients with community-acquired pneumonia (CAP), 171 patient with hospital-acquired pneumonia (HAP) and 197 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)⁵. CAP was defined as acquired pneumonia outside the hospital¹¹. HAP was defined as a pneumonia occurring 48 hours or more after admission, which was not developed at the time of admission¹². AECOPD were defined according to the GOLD guidelines⁵. Patient data were collected using questionnaire including personal data, clinical symptoms, signs, and history of preexisting chronic diseases.  Samples included sputum or bronchoalveolar lavage (BAL) for staining and culture. Samples were cultured on 3 bacteriological media. Blood agar aerobically, chocolate agar with Co₂ and LJ slope then cultures were examined for possible bacterial pathogens of LRTI.  Possible bacterial pathogens were isolated and identified using standard laboratory techniques, and microbial sensitivity testing was carried out by means of disc diffusion for selected antibiotics.

Data analysis

The data was statistically analyzed using EPI-Info version 6. The difference in the distribution of bacterial causes among groups was based on a comparison of frequency distributions by chi-square test. The value of p <0.05 was considered significant.

Table 1: Distribution of age groups, gender and years among LRTI patients and its correlation with bacterial growth outcome.

RESULTS

A total of 555 LRTIs hospitalized patients (328/59.1% male and 227/40.9% female) were enrolled in this study.  The most frequent age groups were 30-42 years (26.5%), and age group 43-56 years (22.5%); while children age group was less frequent (8.5%). Bacterial growth yielded on 354 (63.8%) while 201 (36.2%)

 were negative for bacterial culture (Table 1). A large number of LRTI (36.2%) was not diagnosed, mostly in CAP (52.4%), followed by HAP (33.9%) while lower cases were in AECOPD (22.8%). The isolates in 187 patients with CAP were K. pneumoniae  (26.2%), S. pyogens (12.3%), and S. pneumoniae (9%). Isolates in 171 patients with HAP were MSSA (24%), E. Coli (12.9%), MRAS (11.1%), K. pneumoniae (10.5%) and P. aeruginosa (7%). The organisms in 197 patients with AECOPD were Moraxella catarrhalis (47.2%), K. pneumoniae (17.2%), H. influnzae (10.7%) and P. aeruginosa (2%) (Table 2).  Table 3 shows the frequency of bacterial causative agents of LRTI; the Subtotal Gram positive bacteria were counted for 28.3% from total bacteria isolates, while subtotal Gram positive bacteria was counted for 71.7% from the total bacterial isolates. The most 3 predominant bacteria isolated from LRTIs patients in the study were  K. pneumoniae 101(18%),   Moraxella catarrhalis 91(16.8%) and  S. aureus 60 (10.8%), while others bacteria such as S. pyogens, S. pneumoniae, H. influnzae, P. aeruginosa, E. coli and Proteus vulgaris were less frequent (Table 3). In Gram-positive bacteria high resistance was recorded for ampicillin/sulbactam (100%) and amoxicillin/clavulanate (100%), while a moderate sensitivity rate for amikacin, vancomycin, cefepime and moxifloxacin was recorded. In Gram-negative bacteria, a high resistance to 3g of cephalosporins (68.5%) was recorded, while moderate sensitivity to other tested antibiotics was recorded (Table 4). The rates of cure, ICU admission, isolation and death among LRTI cases of positive bacterial growth were almost similar to those of negative culture with slight differences. The mortality rate among total LRTIs was 25%, while for confirmed LRTI cases in bacterial culture it was 22.9%, which is lower among the LRTI cases of negative culture (28.9%) (Table 5).

Table 2. Bacterial profile of lower respiratory tract infections in Yemen.

CAP: Community-acquired pneumonia; HAP: Hospital-acquired pneumonia; AECOPD; Acute exacerbations of chronic obstructive pulmonary disease; MRSA: Methecillin-resistant Staphylococcus aureus; MSSA: Methecillin-sensitive Staphylococcus aureus.

DISCUSSION

Lower respiratory tract infection (LRTIs) is the leading cause of infectious diseases of death worldwide, the fifth general cause of death, and the second general cause of disability adjusted life years (DALYs), although they are largely preventable causes of diseases and Death¹. In the current study the mortality rate among total LRTIs was 25%, while for LRTIs cases confirmed for bacterial culture was 22.9%, lower than that among negative culture LRTI cases (28.9%) (Table 5); this rate is higher than that reported by Brown and others in the United States of America where the death rate among community-acquired pneumonia hospitalizations patients was 7.4%¹³. While Global Strategy for the Diagnosis, Management and Prevention of COPD, reported that long-term prognosis following LRTIs was poor, with a 5-year mortality of approximately 50%¹⁴. The high mortality rate in the current study may be high rates for related factors and include comorbidities especially cardiovascular disease, severity of exacerbations, age, previous hospitalization, low BMI and malnutrition¹. When reviewing the various studies, it is clear that there are some regional differences in the reported etiology of LRTIs, as described by Waterer¹⁵. This may be related to a number of factors, but it is also important to realize that although LRTIs are not a seasonal disease, many different organisms, including S. pneumoniae, influenza virus, Legionella species infections, and even polymicrobial infections do have seasonal variations¹⁶. 

Table 3: The frequency of bacterial causative agents of LRTI

In the current study the most 3 predominant bacteria isolated from LRTIs patients  were  K. pneumoniae 101(18%),   Moraxella catarrhalis 91(16.8%) and  S. aureus 60(10.8%), while S.pneumoniae and  H. influnzae were less frequently (Table 3); this result is different from that  traditionally, the S. pneumoniae has been reported to be the mainly widespread cause of LRTIs^17-19 and the Global Burden of Disease Study analysis of LRTIs (2015)¹ revealed that the S. pneumoniae was the most common cause of LRTIs among all ages. In spite of this, our results is go with repots in which there have been changes noted in the reported etiology of LRTIs, particularly with the use of more sensitive diagnostic tools^19-21. In wide-ranging, it is gradually more recognized that viruses look to play a bigger role in the etiology of LRTIs than has previously been documented^22-25 and cases of infection with more than one pathogen, commonly the association of one or more viruses with one or more bacterial agents are not uncommon^21,22.

Table 4: Antibiotic sensitivity and resistance rates (percentages) of  gram positive and gram negative bacteria  in 354 patients with LRTI in Yemen

*Not done for P. aeruginosa,  ND= not done

Table 5: The output of LRTI cases  with bacterial infections  in comparison with LRTI cases caused by other agents

For patients with CAP, our results (Table 2) showed bacterial profiles similar to those reported by international studies⁶ and regional²⁶. This pattern of "local" hegemony should be taken into account when prescribing antimicrobials in our region. When antibiotic sensitivity was considering for bacterial isolates from LRTI patients, in Gram positive bacteria a high resistance was recorded for ampicillin/sulbactam (100%) and amoxicillin/clavulanate (100%), while moderate of sensitivity was recorded for amikacin, vancomycin, Cefepime and moxifloxacin.  In Gram negative bacteria a high resistance was recorded for 3^rd g Cephalosporin’s (68.5%), while moderate of sensitivity was recorded for other tested antibiotics (Table 4). Our data revealed high resistance rates for cephalosporins, and the β-lactam-β-lactamase inhibitors. These findings are in agreement with the increasing prevalence of resistance of Gram positive bacteria as S. pneumoniae to those antimicrobial groups, by regional^7,27-29, and worldwide^6,7 studies. Moreover, our results highlight the increasing problem of MDR in Gram positive and Gram negative bacteria  of LRTIs, a problem that was extensively addressed in the literature^28-30.  This warns us of the need for wise use of different groups of antimicrobials, especially in our resource-poor country. Moreover, this requires greater focus on identifying drivers of resistance relevant and on implementing effective strategies to combat resistance and MDR problems. For patients with HAP, the difficulty of antibiotic resistance appears more important; as a result, the situation is more complex than that in CAP. Nosocomial pneumonias leads to high morbidity and mortality, in particular amongst ICU patients^8,11. In most clinical cases, it is needed to start empirical antimicrobial therapy before obtaining microbial results. On the other hand, the situation is further complicated by the emergence of several beta-lactamase and MDR pathogens^29,31. Obviously there is a great need to obtain data on the prevalent strains in HAP; along with the sensitivity pattern to help revise antibiotic policy and guide physicians to better manage patients with HAP; especially in developing countries such as Yemen. The current study revealed the present of MRSA, Gram-negative organisms, and P. aeruginosa among patients with HAP. This differs clearly from the results obtained by Goel and co-workers³¹ and even those of Ahmed, et al.,³², Agmy, et al.,³³. Although the later study addressed the problem of HAP in 75 cases of ICU patients, the predominant pathogens were S.aureus (32%), P. aeruginosa (30%), and S. pneumoniae (15%). It is clear that this "regional" difference explains the changing pattern of pathogens that cause over time, even in the same hospital. This underscores the importance of implementing continued local monitoring programs⁸.  Also, our data show an alarming high prevalence of MRSA. This coincides with the recent report by Alyahawi, and Al-Safani et al.,^34,35 who observed that the prevalence of MRSA in invasive isolates from hospitals in Yemen  was 23%³⁴. 

CONCLUSION

Lower respiratory infections are still very common and continue to be a major cause of morbidity and mortality in Yemen in children and adults alike, and there are significant changes in the epidemiology of LRTIs in terms of their frequency and infectious pathogens. There is a high rate of undiagnosed LRTI in Yemen and this highlights the need for health authorities to develop strategies to diagnose most of the causes of LRTI, including Mycoplasma, Chlamydia, and viral causes. The most common bacteria in CAP in Yemen is  K. pneumoniae while HAP is the S. aureus and Gram negative bacteria. For acute exacerbation of COPD, M. catarrahalis was the most common. No antibiotics are completely effective in treating LRTI in our area and antibiotic sensitivity should be performed in all cases.

ACKNOWLEDGMENTS 

The authors would like to acknowledge Ministry of Health and Population, Sana’a, Yemen and the National Center of Public Health Laboratories (NCPHL), Ministry of Health and Population, Sana'a, Yemen for their support and provided working space and materials.

AUTHOR'S CONTRIBUTION

 This research work is part of project of the National Center for Public Health Laboratories (NCPHL). The authors performed clinical and laboratory works. The corresponding author (HAA) supervised the laboratory works, and revised and edited the research.

CONFLICT OF INTEREST 

No conflict of interest associated with this work. 

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