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Lupine Publishers|Antibiotic Resistance Pattern of Nesseria Gonorrhoea at the Genitourinary Medicine Clinic, Hospital Kuala Lumpur, Malaysia

Lupine Publishers | Journal of Health Research and Reviews

Abstract

Background: In the era of super bugs, there is a need to monitor antibiotic resistance patterns. Due to the emergence of antimicrobial resistance worldwide, local antibiotic resistance patterns should be monitored periodically to alert early intervention. This audit was conducted to analyse the antibiotic resistance patterns among the gonococcal urethritis cases that presented to the Genitourinary Medicine (GUM) Clinic, Hospital Kuala Lumpur (HKL), Malaysia.
Methodology: This is a retrospective study on the antibiotic resistance patterns based on 370 culture positive gonorrhoea obtained from urethral swab samples sent between 2011 and 2015. Antimicrobial susceptibility testing by standard disc diffusion method was performed to detect sensitivity to penicillin, tetracycline, ciprofloxacin, cefuroxime, azithromycin and ceftriaxone. All data was obtained from microbiology report and patient records.
Results: A total of 370 positive culture isolates of N.gonorrhoeae (new and recurrent cases) from 2011 to 2015 were reviewed. Highest level of resistance detected was to azithromycin (100%, 64/64) followed by tetracycline (82.8%, 293/354). Resistance to penicillin was noted in 60.9% (224/368) of all isolates. Both penicillin and tetracycline showed a decreasing resistance trend from 2011-2015. The fourth commonest antibiotic resistance was to ciprofloxacin at 46.5% (158/340). Cephalosporins tested were cefuroxime and ceftriaxone, which showed resistance rates of 2.7% (6/219) and 0.8% (3/364), respectively.
Conclusion: The complete resistance to azithromycin is alarming since it is a common antibiotic used to treat urethral discharge using the syndromic approach. Penicillin and tetracycline resistance remain high in Malaysia and other Western Pacific countries. The current first line antibiotic for treating gonorrhoea in GUM Clinic, HKL is ceftriaxone. Clinicians should be aware of the newly discovered increase in resistance observed to ceftriaxone.
Keywords: Neisseria gonorrhoeae; Gonorrhoea; Antibiotic Resistance

Introduction

The last decade has seen Neisseria gonorrhoeae emerging as a true superbug, bringing.com closer to a time of untreatable gonorrhoea. This diplococcal microbe is able to recombine its genes and invade the immune system through antigenic variation. It is also naturally competent to acquire new deoxyribonucleic acid (DNA), enabling N. gonorrhoeae to spread new genes, disguise itself with different surface proteins, and prevent the development of immunological memory an ability that has led to antibiotic resistance and has made vaccine development difficult. Gonorrhea is a debilitating disease, which was responsible for an estimated 445,000 years lived with disability in 2015, according to a systemic analysis for the Global Burden of Disease Study [1]. Patients infected with N.gonorrhoeae are known to present with urethral discharge, malaise and symptoms that may suggest a urinary tract infection. Nevertheless, urogenital gonorrhea may be asymptomatic in 40% of men and often manifests as urethritis [2,3].
Unfortunately, it is also asymptomatic in more than half of women [4]. In men, untreated urethral infection can lead to epididymitis, reduced fertility, and cause urethral strictures. In women, if present, symptoms are non specific and include abnormal vaginal discharge, dysuria, lower abdominal discomfort, and dyspareunia. The lack of discernible symptoms results in unrecognized and untreated infections, which can lead to serious complications [5]. Overall, 10%-20% of female patients develop pelvic inflammatory disease (PID) and, consequently, are at risk for infertility [6]. Pregnancy complications associated with gonorrhea include chorioamnionitis, premature rupture of membranes, preterm birth, ectopic pregnancies, and spontaneous abortions [5,7,8]. Infants of mothers with gonococcal infection can be infected at delivery, resulting in neonatal conjunctivitis (ophthalmia neonatorum). Such untreated conjunctivitis may lead to scarring and blindness.
Extragenital infections are common in both sexes and frequently occur in the absence of urogenital infection [9,10]. Rectal infections are usually asymptomatic but can manifest as rectal and anal pain or discharge. Pharyngeal infections are mostly asymptomatic, but mild sore throat and pharyngitis may occur. Although bacterial concentrations are generally lower than in other infection sites, the pharynx is thought to be a favourable site for resistance emergence due to acquisition of resistance traits from commensal Neisseria spp [11]. Disseminated gonococcal infections with gonococcal arthritis also occur. Because they are frequently asymptomatic, extragenital infections often remain untreated, despite their key role in disease transmission. Co-infection with other major Sexually Transmitted Infections (STIs) HIV, Herpes simplex virus, Chlamydia trachomatis, Mycoplasma genitalium, and Treponema pallidum are common and may result in synergistic effects on transmission and disease severity. Attempts to treat and control gonorrhoea are compromised by the emergence and spread of antibiotic resistant N.gonorrhoeae. Antibiotic resistance pattern vary between different geographical areas. It is therefore important to know the local antibiotic resistance pattern, so that appropriate treatment can be instituted. In Malaysia, Kanamycin was used as the first line antibiotic to treat gonorrhoea during the early 1970’s and 80’s, which was subsequently changed to Spectinomycin, followed by Ceftriaxone since the early 1990’s [12] There are many surveillance programmes on antibiotic resistance patterns of N.gonorrhoeae such as GRASP (Gonococcal Resistance to Antimicrobial Surveilance Programme), that is based in London, UK, and WHO (World Health Organization) Antimicrobial Surveilance Programme [13,14].

Materials and Methods

All patients with positive culture for gonorrhoea, who attended the GUM clinic in HKL between 2011-2015, were included in this study. Antimicrobial susceptibility testing by standard disc diffusion method was performed to detect sensitivity to Penicillin, Tetracycline, Ciprofloxacin, Cefuroxime, Azithromycin and Ceftriaxone. Data was obtained from patient records and formal microbiology laboratory results.

Results

370 positive culture isolates of N.gonorrhoeae from patients seen in 2011-2015 were included in this study. Most of the data were obtained from the microbiology laboratory results. Demographic data was available for 98 patients only. More than half of the patients (58.2%) were between 21-30 years old. Most patients were Malay (83.7%), followed by Indian (9.2%). Overall, the heterosexually orientated patients represented about 73% of gonococcal urethritis cases. Majority of cases (92%) tested negative for HIV (Tables 1 & 2). The highest level of resistance detected was to azithromycin (100%, 64/64), followed by tetracycline (82.8%, 293/354). Resistance to penicillin was noted in 60.9% (224/368) of all isolates. Both penicillin and tetracycline showed a decreasing resistance trend from 2011-2014, but increased in 2015. The fourth commonest antibiotic resistance was to ciprofloxacin at 46.5% (158/340), followed by cefuroxime 2.7% (6/219). Resistance to ceftriaxone was 0.8% (3/364), although reviews previously in 2001-2005 showed no resistance [12]. The results were compared to data obtained from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) and WHO (World Health Organization) Antimicrobial Surveillance Programme [13,14].

Table 1: Demographic characteristics of patients with gonorrhoea.

Table 2: Summary of antibiotic resistance pattern of N.gonorrhoeae (2011-2015) in HKL.

Discussion

Azithromycin

The rate of resistance to Azithromycin in this study was higher than expected. All 64 samples tested for sensitivity to Azithromycin showed resistance. In Singapore, no resistance to Azithromycin has been documented [14]. Similarly in England & Wales and Australia, the rate of resistance is significantly lower, at 1% or less [13,14] (Table 3). Studies have indicated concerns for increasing resistance to Azithromycin, likely due to delay in diagnosis of gonorrhoea and suboptimal dose of Azithromycin used [15].

Table 3: Comparison of N.gonorrhoeae antibiotic resistance pattern in HKL with other countries.

Tetracycline

The rate of resistance to Tetracycline is high. In our study, 82.8% of N.gonorrhoea isolates were resistant to Tetracycline. This is slightly lower, compared to an earlier analysis done in HKL from 2001-2005, where 86.8% of isolates were resistant [12]. The resistance rates in England & Wales was similar to ours [13] (Table 3). Looking at the trend, there was a reduction in resistance rates from 87.1% in 2011 to 63.2% in 2014. However, the rate increased to 91.1% in 2015 (Table 2). In HKL, Doxycycline is sometimes used to treat non-gonoccocal urethritis but never as primary treatment for gonorrhoea. Tetracycline has never been used for treating gonorrhoea in HKL as the resistance is very high. Nevertheless, the resistance pattern is continuously monitored for epidemiological purposes.

Penicillin

Since the 1940’s, Penicillin was successfully used to treat gonorrhoea, but quickly developed decreased sensitivity and deemed not a suitable treatment after 1970. This can be due to Penicillinase Producing N.gonorrhoeae (PPNG) or Chromosomal Mediated Resistance N.gonorrhoeae (CMRNG) [16]. Our study shows that the rate of N.gonorrhoeae resistance to Penicillin has reduced, from 82.2% in 2011 to 53.6% in 2015 (Table 2). Compared to an earlier study done in HKL in 2001-2005, there was a slight drop in resistance to penicillin in HKL from 64.4% to 60.9% in 2011-2015. However, our resistance rates were much higher compared to the resistance rate reported in England & Wales of 22.6% (Table 3) [13].

Ciprofloxacin

In the early 1990’s, Ciprofloxacin was widely used especially by general practitioners to treat gonorrhoea although studies had already began demonstrating the beginning of reduced sensitivity to quinolones. The resistance to Ciprofloxacin in HKL showed a steady increase from 10.0% in 2011 to 62.7% in 2015 (Table 2). When compared to an earlier review in HKL from the period 2001- 2005, we can see marked increase in resistance to Ciprofloxacin from 10.4% to 46.5% in 2011-2015 (Table 3). The resistance rate reported in HKL from 2011-2015 was similar to England & Wales and Australia, which reported resistance of 37.3% and 34.7% respectively (Table 3) [13,14]. Among the Asian countries, Singapore reported the lowest resistance to Ciprofloxacin (10.0%) [14]. Other Asian countries, like the Phillipines, Thailand and China reported an alarmingly high resistance to Ciprofloxacin, which is between 74.4%-100% (Table 3) [14].

Cephalosporin–Cefuroxime and Ceftriaxone

Although Cefuroxime is not a recommended treatment for gonorrhoea, its resistance pattern is monitored for epidemiological purposes. Our study showed a resistance rate of 2.7% to Cefuroxime in 2011-2015, whereas an earlier study in 2001-2005 showed no resistance to Cefuroxime (Table 3). Susceptibility testing for Ceftriaxone use in the treatment of gonorrhoea in HKL between 2001-2005 indicated no resistance, however, recent data from 2011-2015 showed a resistance rate of 0.8% (Table 3). Ceftriaxone is the first line treatment of gonorrhoea in HKL and clinicians should be aware that we are seeing a small percentage of resistance in some cases. No resistance was noted in Singapore and the Phillipines (Table 3) [14]. Resistance rates to Ceftriaxone in Thailand and China are significantly higher, at 19.9% and 36.9% respectively (Table 3) [14].

Conclusion

Attempts to treat and control gonorrhoea are compromised by the emergence and spread of antibiotic-resistant N.gonorrhoeae. WHO expert committee has recommended that treatment regimen be altered once resistance to a particular antibiotic reaches 5%. High rates of resistance to Penicillin and Tetracycline have been documented in HKL and in the Western Pacific region. Within 15 years, a marked increase in Ciprofloxacin resistance (10% to 46.5%) is evident. Resistance to Cefuroxime and Ceftriaxone was discovered, which was not found in the previous study. Ceftriaxone remains the first line antibiotic in treating gonorrhoea in HKL, and clinicians need to be aware of the small percentage of resistance detected to Ceftriaxone.

Acknowledgement

We would like to thank the Director General, Ministry of Health, Malaysia for permission to publish this study, and the staff from Genitourinary Medicine Clinic, HKL for data collection.


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Lupine Publishers | Intracardiac Papillary Fibroelastoma: A Case Report

Lupine Publishers | Journal of Health Research and Reviews

Abstract

Most of primary cardiac masses correspond to benign tumors within which are the myxomas, rhabdomyomas and papillary fibroelastomas that occupy the third place in prevalence. These lesions are rare and are usually found incidentally in routine studies. More than 90% of papillary fibroelastomas occur in the heart valves, the most frequent being the aortic valve and the mitral valve. Echocardiography studies have reported a size between 2 and 40mm, mostly corresponding to single lesions, with a short pedicle, which present independent movement and are attached to an endocardial surface. The treatment is surgical since they can present complications like embolism to the pulmonary or systemic circulation, significant hemodynamic obstruction and death secondary to these embolic events. We present the case of an asymptomatic patient in whom a papillary fibroelastoma located in the tricuspid valve was documented, which was successfully resected.
Keywords: Cardiac tumors; papillary fibroelastomas; Embolism; Echocardiography

Introduction

Heart tumors include a wide number of lesions that may be of neoplastic or non neoplastic origin. Primary benign lesions are approximately 90% of primary heart tumors, including myxomas, rhabdomyomas, fibroids, and lipomas, among others [1]. Metastatic lesions are more frequent than primary lesions, found in nearly 18% of stage IV cancer [2]. Most heart tumors are incidentally found during routine cardiac imaging, and their prevalence in autopsy series is less than 0.1% [3-5]. Patients with primary tumors are usually asymptomatic until lesions grow large and generate symptoms related to mechanical obstruction, valve interference, alterations in contractility or in the electrical conduction system, generating arrhythmias and blockages [1,6]. Papillary fibroelastoma is the third most prevalent primary tumor after myxoma and rhabdomyoma. It may compromise valve surface, although cases of compromised interventricular or interatrial septum have also been reported [6,7]. Next we present the case of an asymptomatic patient with papillary fibroelastoma in the tricuspid valve, which was successfully resected.

Case Background

51-year-old man with a history of controlled hypertension and an active smoker, asymptomatic from a cardiovascular point of view who underwent a transthoracic echocardiogram during his routine checkup in his hometown. The exam revealed a mass attached to the tricuspid valve, and thus the patient was referred to our hospital for assessment. He was hemodynamically stable when he checked in at Hospital Militar Central (HMC), with no abnormal findings after physical examination and with normal range of laboratories and preoperative electrocardiogram values. After checking in at the HMC, the patient underwent a transesophageal echocardiogram to better characterize the lesion, which revealed a 11mm x 11 mm rounded, pedunculated mass of endocardial density in the lateral valve (Figure 1), without regurgitation and with preserved ejection fraction of the left ventricle (63%). The remainder of the description of this study was normal. Both the transthoracic and the transesophageal projection show a 11mm x 11 mm rounded, pedunculated mass of endocardial density in the anterior tricuspid valve. The subject underwent additional presurgical testing in the form of a coronary angiography, which revealed epicardial arteries without angiographically significant lesions. The patient’s case was submitted to the Board of Cardiology and to the cardiovascular surgery service, and it was concluded that he was suitable for surgery. The histopathological study of the sample taken in surgery was reported as papillary fibroelastoma type myxoid tissue mass of mesenchymal origin with a low degree of malignancy (Figure 2). The patient evolved without complications during the postoperative period and was discharged after 7 days of hospitalization.

Figure 1: Transthoracic (left) and transesophageal (right) echocardiogram.

Figure 2: Sample of resected mass.

Discussion

Heart tumors or masses are rare lesions that are documented parenthetically when performing a routine cardiac imaging. They can be classified into neoplastic and non-neoplastic tumors, the former being 20 to 50 times more frequent than primary tumors [1,7,8]. The prevalence of primary tumors is very low, being between 0.001 and 0.03% according to reports in autopsy series; as for neoplastic cardiac lesions, they can be found in about 18% of stage IV cancer patients [2-5]. Most primary heart tumors are benign, myxomas being the most frequent in adults, while rhabdomyoma is the most common in children. The third most frequent primary heart tumor in adults is the papillary fibroelastoma, which can be generated on any surface of the endocardium, being more commonly located in the heart valves. It makes up less than 10% of all cardiac tumors and is the most common valve tumor [5,8,9]. Papillary fibromyosarcomas are benign proliferations consisting of soft fibroblasts and variable collagenized stroma derived from the endocardium. They can occur at any age, but are more common in adults between 70 and 80 years. Over 90% of fibroelastomas occur in the heart valves, and close to 10% happen in non-valvular surfaces, such as the interventricular or interatrial septum [1,8]. From a clinical point of view, up to a third of patients are asymptomatic, so their diagnosis is mainly incidental in autopsies, in echocardiographic studies or during a cardiovascular surgery [10-12]. In the case of patients with symptoms, they are secondary to obstructive effects of the coronary ostium or to embolic events in pulmonary or systemic circulation due to detachment of mass fragments or accumulated thrombi that have also been described in cases of sudden death by embolization in coronary arteries and in cases of ischemic cerebrovascular events [1,8,13].
Regarding the findings in echocardiography, the lesions are usually located in the aortic valve, followed by the mitral valve, with a size between 2 and 40 mm, making them easier to detect in transesophageal echocardiograms. The overall mass is unique, with a short pedicle; it moves independently and it is attached to an endocardium surface. Given that the tumor has papillary extensions attached to the central pedicle, an image in the shape of a sea anemone is observed. Sometimes it is difficult to differentiate the lesion when it is attached to the valves when they are moving and when they are smaller than 2 mm [5,8]. Although the papillary fibroelastoma can be seen in the Computerized Axial Tomography and the Nuclear Magnetic Resonance, the echocardiogram is still the best image to evaluate these lesions since they are highly mobile and can be better seen in high resolution mode or zoom mode. Larger lesions may be accompanied by calcifications, which makes it easier to identify them [1,5]. The differential imaging diagnoses of this type of tumors include Lambal’s excrescences, which look more linear and are smaller, the vegetations that are usually accompanied by valve incompetence and destruction of the valve leaflets, thrombi and valve degenerative changes. Although these tumors are formed in the heart valves, the dysfunction of these structures is rare [5,8,10]. Treatment of benign primary tumors such as papillary fibroelastoma is surgical. Some authors suggest that, in the case of tumors on the left side, they should be resected in patients without high surgical risk if the size is greater than 1 cm or during another type of heart surgery. In the case of lesions on right side of the heart, they should only be resected if they are large or moving, and if they are associated with a hemodynamically significant obstruction or with a high risk of embolism due to short circuit from right to left [5,14]. Although a significant percentage of patients are asymptomatic, we suggest that those that meet the aforementioned criteria be resected, given the high risk of cerebrovascular events and death, aiming to use a technique that conserves the native valve [1,15]. If the patient does not have any symptoms or if the tumor is small, has no pedicle and is not moving, of if it is not possible to perform the surgical procedure due high surgical risk or due to the patient’s preference, we suggest antiplatelet therapy, even though there are few publications that support this recommendation [5,15].

Conclusion

Primary cardiac fibroelastoma of the papillary fibroelastoma type are rare masses that are usually found incidentally during routine exams conducted to frequently asymptomatic patients. The image that can best characterize this type of mass is the transesophageal echocardiogram and the recommended management is surgery, considering the risk of embolic events and the individual characteristics of both the patient and the tumor,

Ethical Responsibilities

Protection of people and animals. The authors declare that no experiments have been conducted on humans or animals for this research.
a. Data Confidentiality: The authors declare that they have followed the protocols of their work center on the publication of patient data. Right to privacy and informed consent. The authors declare that patient data does not appear in this paper.

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