Vancomycin Resistance Streptococcus pneumoniae,a Case Report

Abstract

Streptococcus pneumoniae is a pathogenic bacterium that causes invasive pneumococcal disease in humans, especially pediatric patients. Antibiotics are primary therapeutic agents. Resistance to antibiotics is a growing health problem, and healthcare authorities have warned that 10 million people will die each year by 2050 and become the first killer. To date, resistance to vancomycin has not been recorded in Iraq. This study reports a 9-month-old infant presented with fever, irritability, crying, and decreased oral intake for 3 days. Cerebrospinal fluid (CSF) parameters included turbid appearance, pleocytosis, and high protein and low sugar levels. Culture and sensitivity tests revealed the growth of Streptococcus pneumoniae, which is resistant to vancomycin. Reporting vancomycin resistance in Streptococcus pneumonia adds to the growing body of research on the pandemic of drug resistance. It indicates when all antibiotics are ineffective, as in the pre-antibiotic era, and this needs a more comprehensive plan.

Introduction

Streptococcus pneumoniae is an aerobic, gram-positive Diplococcus bacterium that undergoes partial or complete hemolysis under different conditions, and the bacteria are sensitive to optochin, which differentiates it from normal flora such as Viridance Streptococci. ¹ To date, more than 100 serotypes of this pathogen have been identified, which differ in pathogenicity, prevalence, and toxicity. ² This pathogen causes a significant health burden in clinical settings, including meningitis, bacteremia, and pneumonia. It is also associated with high morbidity and mortality rates. Invasive Pneumococcal Disease (IPD) is the leading cause of 1.6 million deaths each year. Most victims are children below 5 years of age, ³ specifically those aged <2 years. ⁴

As a public health strategy, the World Health Program (WHO) recommended the global pneumococcal vaccine in national immunization programs. Iraq joined the use of the pneumococcal vaccine in 2017. ⁵ High morbidity and mortality rates necessitate the prompt use of antibiotics. The readiness for antibiotics has a dramatic effect on decreasing child mortality and increasing life expectancy. ⁶ However, increasing resistance to current antibiotics is the leading cause of multi-drug resistant (MDR) bacteria, which complicates clinical outcomes. ⁷ Notably, healthcare authorities are alarmed by rising infectious diseases and call to prevent and reduce infections by antibiotic-resistant bacteria

Currently, there are 700 000 deaths per year due to antibiotic resistance, and it is predicted to lose 10 million/year by 2050. ⁸ One of the main factors of this threat is overusing or using antibiotics carelessly in a variety of settings, particularly clinical treatment, animal healthcare, the food system, and agriculture. ⁹ Resistance of Streptococcus pneumoniae to antibiotics is a continuous and risky health problem worldwide, especially for widely used antibiotics such as β-lactams, fluoroquinolones, and macrolides. ¹⁰ Vancomycin serves as the final line of defense against bacteria that have become resistant to other antibiotics, including streptococcus pneumonia infections. ¹¹

Vancomycin is an effective antimicrobial agent for the treatment of Streptococcus pneumonia, and according to published literature, bacteria are still sensitive to vancomycin.^1,4 There is no reliable evidence that streptococcus pneumonia is resistant to vancomycin in Iraq. Therefore, this paper discusses a case of meningitis due to Streptococcus pneumonia that resists vancomycin. Recently, with the emergence of an outbreak of meningitis among children in Iraq, ¹² after obtaining written informed consent from the parents, we recorded the first case of Streptococcus pneumonia that resists vancomycin.

Case Presentations

Patient Information

A 9-month-old boy presented with fever, irritability, decreased oral intake, decreased sleep for 3 days, no vomiting, no diarrhea, no history of trauma, no prior history of admission, and he didn’t receive any vaccines. The family visited the hospital a day before admission, and initial examinations and investigations were not significant, and they were treated as outpatients with antipyretics; the day after, the patient returned with no improvement.

Clinical Findings

After admission, the infant was conscious, irritable, crying most of the time, looked ill, dehydrated, feverish (temperature, 39°C from axillary), and had no abnormal body movements. On examination, tense fontanels with normal cardiovascular, respiratory, skin, and eye systems.

Diagnostic Measures

After admission, the initial investigations were normal, including (complete blood counts, urine tests, renal and liver functions, electrolytes, blood sugar, and chest X-ray). However, C-reactive protein level was high (206.44 mg/dl). As part of the septic screening, we performed a lumbar puncture and collected 3 CSF specimens. The CSF findings were; turbid, pleocytosis, low CSF sugar, high protein, and high bacterial counts were observed under an ordinary microscope. On Gram staining, purple, spherical Diplococcus bacteria were observed (Figure 1). CSF was added to blood, chocolate, and MacConKey Agar from the second specimen. After 24 hours, growth was observed on blood and chocolate but not MacConKey Agar. At the same time, there was hemolysis around the colonies on blood agar. For the antibacterial sensitivity test (AST), Muller-Hinton agar was used, and several antibiotics, including vancomycin, were added to the media using the disk diffusion method (DDM) (Table 1). After 24 hours of incubation at 37°C, no clear zone for vancomycin was observed. Before the culture and sensitivity results returned, treatment was started, usually double antibiotics (ceftriaxone, vancomycin), dexamethasone, antipyretics, and fluid, with monitoring.

Figure 1.

View of Streptococcus Pneumoniae in the CSF of the infant after gram stain under a microscope.

Table 1.

Antibiotic Susceptibility of Streptococcus pneumoniae in Our Patient.

Antibiotics	Disk content (mcg)	MIC	Sensitivity	Intermediately susceptible	Resistance	Interpretation
Amikacin	30	8	≥17	15-16	≤14	R
Ampicillin	10	8	≥17	14-16	≤13	R
Amoxicillin/clavulanic acid	20/10	7	≥18	14-17	≤13	R
Cefdinir	5	10	≥20	17-19	≤16	R
Cefixime	5	10	≥19	16-18	≤15	R
Ciprofloxacin	30	10	≥21	16-20	≤15	R
Imipenem	10	10	≥16	14-15	≤13	R
levofloxacine	5	8	≥17	14-16	≤13	R
Meropenem	10	10	≥16	14-15	≤13	R
Moxifloxacine	5	10	≥18	15-17	≤14	R
Vancomycin	30	8	≥17	15-16	≤14	R
Ceftazidim	30	10	≥18	15-17	≤14	R
Ceftriaxone	30	8	≥21	14-20	≤13	R

Abbreviation: R, resistance.

Treatment and Follow Up

Based on the results of sensitivity (Table 1), antibiotics were manipulated, and piperacillin/tazobactam (PIPC/TAZ) was initiated, although there is no insurance coverage for its use in patients with meningitis, the penetration of PIPC/TAZ into CSF in animal experiments promises a satisfactory result, as well as in many clinical trials with good outcome. ¹³ Similarly, our case showed gradual improvement in signs and symptoms, and remained in the hospital for 14 days and received and completed the course of treatment. During admission and later on, serial head circumference was measured, and cranial ultrasound, Computerized Tomography of the brain, and magnetic resonance imaging of the brain were all normal.

Discussion

The introduction of antibiotics in used medicine was a breakthrough and revolution, and antibiotics were used not only to treat lethal infections but also made some potential procedures possible, such as treating cancer patients, organ transplantations, and prosthetic valve replacement. ¹⁴ However, after a century of discovery of this miracle, health authorities are alarmed to be the first killer in 21 centuries, owing to the emergence of antibiotic resistance. Streptococcus pneumoniae is a gram-positive bacterium that causes pneumonia, bacteremia, and meningitis. Different antibiotics are used to treat this pathogen, including beta-lactam antibiotics, cephalosporins, aminoglycosides, quinolones, and vancomycin. ¹⁰ Several studies have reported the antibiotic susceptibility of Streptococcus pneumoniae to various antibiotics. Tsai et al ¹⁵ reported that 85.7% of bacterial strains were non-susceptible to penicillin, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7%, and the susceptibility to vancomycin was 100%. In a study that determined the resistance rate of Streptococcus pneumoniae among cancer patients in Brazil, Cardoso et al ¹⁶ found that non-susceptibility to various antibiotics ranged from 14% to 40%, while susceptibility to vancomycin was 100%. In another study by Ali et al ¹⁷ in Pakistan, the resistance rate to amoxicillin was 100%, whereas the susceptibility to vancomycin was 100%. To examine this issue, Kim et al carried out a series of antibiotic susceptibility tests on these bacteria in Korea. They reported non-susceptibility to cefotaxime, ceftriaxone, clindamycin, penicillin, and levofloxacin (27.2%, 21.6%, 68.8%, and 18.1%, respectively) without any resistance to vancomycin. ¹ In contrast to previous studies Novak et al ¹⁸ argued that Streptococcus pneumoniae had resistance to vancomycin, similar to the finding of the present study. Perhaps the most clinically relevant finding in the current study is the recording of the first case of Streptococcus pneumoniae meningitis that resists vancomycin in Iraq. To the best of our knowledge, this result has not previously been documented.

In the current study, some limitations need to be acknowledged, such as the culturing process performed by manual methods compared to devices such as VITEC 2, which have less reliable outcomes. On the other hand, the key strength of the present study is that all manual procedures were according to WHO guidelines and recommendations. Further studies are required to understand better the efficacy and safety of vancomycin against streptococcus pneumonia. Based on the results of this study, several important changes need to be made, such as proper antibiotic use, implementation of antibiotic stewardship programs in clinical settings, and the search for alternative antibiotics.

Conclusion

The results of this study suggest that antibiotic resistance is evolving. These findings indicate that Streptococcus pneumoniae starts to resist vancomycin, the last line of antibiotics against bacteria. These findings may have a bearing on the management of critically ill patients. This is the first study to report vancomycin resistance in Streptococcus pneumoniae, and the findings add to the growing body of research that indicates the time may come when all antibiotics are ineffective, as in the pre-antibiotic era.