A Rare Complication of Proteus Brain Abscess Due to Coccidioidomycosis Causing Hydrocephalus

Abstract

Proteus mirabilis is a very common gram-negative facultative anaerobe seen in urinary tract infections. This rod-shaped bacterium tends to cause urolithiasis via its ability to alkalinize the urine. However, in some cases, this bacterium has been shown to cause bacteremia as well as other complicated infections. Here we would like to present a rare case of Proteus mirabilis that has invaded the brain in a patient that has a ventriculoperitoneal (VP) shunt placed due to coccidioidal meningitis causing hydrocephalus. We would also like to discuss the importance of the monitoring of VP shunt and discuss their likelihood of infections and the medical as well as surgical management.

Introduction

Hydrocephalus is a condition resulting in an inappropriate excess in cerebrospinal fluid (CSF) which accumulates in the subarachnoid spaces and/or cerebral ventricles leading to dilatation of said ventricles. ¹ It is caused by a variety of factors and is treated based on whether the disease causing the pathology can be properly addressed. However, in patients who continue to have hydrocephalus, surgical management might be warranted. One such procedure is a ventriculoperitoneal (VP) shunt which attempts to divert the CSF from the lateral ventricles into the peritoneal cavity through a catheter. ² Most standardized protocols that involve VP shunt placement tend to have significantly reduced infections; however, they can still occur. ² Despite this VP shunt in general has become tantamount to reducing hydrocephalus. Other key important devices are external ventricular drain (EVD) and/or Ommaya reservoirs that can also be placed; however, their rates of infection are still significant although varied. One systematic study that observed 5733 EVD placements revealed positive CSF cultures that ranged between 2.3% and 23%. ³ For Ommaya reservoirs 1 study had shown, a prevalent rate of infection from 7% to 50%, with a 20 times increase in infections of patients who used the reservoir more frequently due to treatment for their lymphoproliferative disorders. ⁴ Other complications can also occur such as intracerebral hemorrhage from catheter placement, seizures, shunt malfunction, and so on. Regardless infections tend to be more commonplace. In fact, in prior studies, cultures have been shown to grow a myriad of bacterial species such as Staphylococcus aureus, Corynebacterium species (spp), Bacteroides spp, and Fusobacterium spp. ⁵ In other cases, fungal species were seen in cultures like Candida parapsilosis, and Cryptococcus neoformans.^6,7 In some cases, less common bacterium can infect these shunts, and one such bacterium that is able to colonize around a VP shunt resulting in a brain abscess is proteus mirabilis. ⁸

Proteus mirabilis is a gram-negative bacterium known for its flagella and fimbriae that gives it a swarming motility. Another one of its key abilities is to secrete urease and alkalinize its environment. ⁹ As a result, this bacterium tends to be associated with struvite stones along with catheter-associated urinary tract infections. ¹⁰ Due to its ability to colonize the genitourinary tract, infections related to this bacterium that occur in other organ systems do come about but at a lower frequency. In some instances, this microorganism has been shown to create intracranial abscesses. ¹¹ Here we would like to present a rare case of Proteus mirabilis ability to create a brain abscess via a ventricular shunt. A discussion regarding the complications of these shunts as well as the importance of monitoring and management will be included.

Case Presentation

A 63-year-old male with a prior history of coccidiomycosis and liver cirrhosis previously on Isavuconazole presents to the emergency department after being brought by emergency medical services with complaints of confusion, tremors, and weakness for the past 3 days. History was obtained from the patient’s sister who stated that the patient was independent and able to do daily activities at baseline. However, the patient’s sister noted that the patient was being more nonsensical and having an ataxic gait. Of note, the patient had failed fluconazole treatment due to side effects and was non-compliant with his Isavuconazole.

Patient vitals showed that he was mildly bradypneic but otherwise saturating well on room air and all other vitals were unremarkable. He was noted to be only oriented to self and unable to follow commands. The rest of the physical exam was unremarkable. Shortly after, a full altered mental status workup was ordered and complete metabolic panel, urinalysis/urine culture, thyroid function panel, urine toxicology, HbA1c, blood glucose, ESR (Erythrocyte sedimentation rate), CRP (C reactive protein), HIV (Human Immunodeficiency Virus), hepatitis panel, and syphilis titers were unremarkable. CBC (Complete blood count) showed thrombocytopenia with platelets in the 40s which was attributed to the patient’s history of alcoholic liver cirrhosis and elevated bands in the low 20s but otherwise unremarkable. CT scan of the head without contrast was ordered due to concerns of trauma and or brain bleed that could have led to an altered mental status due to the patient’s ataxic gait. A lumbar puncture was also performed with CSF cultures in the interim, while CT (Computed Tomography) scan results were pending. CSF (Cerebrospinal fluid) cultures were negative but coccidiomycosis blood titers show weakly reactive IgM and strong IgG response with a titer of 1:128, indicating that the patient has a history of coccidiomycosis with a current active infection. CT scan demonstrated enlargement of the ventricles with periventricular edema most likely secondary to increased CSF with no evidence of infarction, trauma, hemorrhage, or mass (Figure 1).

Figure 1.

The figure above shows severe communicating hydrocephalus present within the lateral ventricles.

Multiple lumbar punctures were done for CSF removal and neurosurgery was consulted for VP shunt placement. Infectious disease was consulted for further management. The patient was started on Amphotericin B and Isavuconazole 372 mg IV daily for concerns of coccidioidomycosis-induced hydrocephalus. He was transfused 2 units of platelets, given perioperative vancomycin, and a VP shunt was placed (Figure 2). The patient was monitored, and his mentation, gait, and other symptoms slowly improved over the course of a few weeks. A repeat CT scan of the head without contrast (Figure 3) showed a decrease in ventricular prominence on the lateral ventricles. The patient continued his Amphotericin B treatment and was eventually discharged to a skilled nursing facility for physical and occupational therapy while continuing Isavuconazole.

Figure 2.

This CT head without contrast shows there is interval placement of the right frontal VP shunt catheter with the tip placed in the left lateral ventricle with no signs of hemorrhage.

Figure 3.

The lateral ventricles in this coronal CT scan depict not only the VP shunt in place but also a decrease in size from the frontal horns currently measuring 38.4 mm when compared with 46.4 mm prior in Figure 1a.

Shortly after, the patient had returned from his skilled nursing facility due to worsening mentation being only oriented to self and unable to follow commands. A repeat altered mental status workup was done which showed similar results as prior. Another head CT without contrast was done showing worsening right frontal hypodensity with a questionable collection surrounding the ventriculostomy catheter with concerns for abscess resulting in catheter failure (Figure 4). CT scan also re-demonstrated re-accumulation of CSF. A magnetic resonance imaging (MRI) of the brain with and without contrast was done to further access the collection. A lumbar puncture was done, and CSF was sent for culture and gram stain. Neurosurgery was consulted, and a decision to remove the VP shunt and place an EVD was made. Cultures initially grew gram-negative rods, and the patient was started on cefepime 2 g q8h. However, cultures soon revealed that the patient was growing Proteus mirabilis, and the patient was switched to ceftriaxone 2 g q12. The patient was continued on a regimen of Isavuconazole 372 mg daily. MRI showed an abscess measuring 27 × 17 mm surrounding the shunt path and metronidazole 500 mg 3 times daily was added due to the likely intra-abdominal source of the pathogen (Figure 5). The patient was able to follow some commands but only oriented to self. EVD was noted to be draining approximately 100 to 200 mL of fluid. Over the next few days patient’s mentation slowly improved, and he was noted to be oriented to self, situation, time, and place. EVD was draining minimal fluid and was shortly removed due to decreased output, and neurosurgery recommended that the patient avoid any shunts in the upcoming future. The patient was noted to have slight improvement; however, the following day, the patient developed mildly worsening mentation once more. Another CT scan of the head without contrast was done which showed moderately severe hydrocephalus with gas in the lateral ventricles, particularly in the frontal horns (Figure 6). The patient was continued on antibiotics and antifungal medication; however, his mentation did not improve. After a discussion with the patient family, it was decided to send the patient home with hospice given his poor prognosis and outcome.

Figure 4.

The red circle shows increasing right frontal lobe hypoattenuation with questionable collection surrounding the ventriculostomy catheter.

Figure 5.

The MRI of the brain shows that there is a large area of vasogenic edema in the superior right frontal lobe measuring at approximately 63 × 37 mm. At the center of the edema, there is a ring-like enhancing lesion with a thick wall slightly thinner on the medial aspect suggesting an abscess.

Figure 6.

This CT of the head portrays gas in the lateral ventricle in the frontal horns.

Discussion

To prevent shunt infections, sterile surgical techniques along with perioperative antibiotic prophylaxis should be considered the gold standard.^12,13 One meta-analysis study had found that systemic antibiotics that were given prophylactically for ventricular shunt placement tend to decrease rates of CSF shunt infections. ¹⁴

However, complications can still occur in surgical procedures, and as such, close monitoring and care should be done for the patient. Although our patient had received 1 g of vancomycin throughout the procedure, he had not received any antibiotics postoperatively. This is the current recommended guidelines for surgical antimicrobial prophylaxis, which do not require any postoperative antibiotics. ¹³ This is understandable since prior studies have argued abstaining from prolonged antibiotic prophylaxis when placing shunts particularly EVD due to concerns of resistant bacteria. ¹⁵ Albeit, the same study that argued against prolonged antibiotic prophylaxis recommends continuing antibiotics for 24 hours postoperatively, particularly vancomycin. This is because most CSF shunt infections tend to be coagulase-negative staphylococci. ¹⁵ The same study also recommended the use of antibiotic-impregnated devices since they have been shown to reduce EVD and CSF shunt infections. ¹⁵

Meta-analyses studies have shown a reduction of infection with the use of antibiotic-impregnated catheters with 1 study comparing standard VP shunts to antibiotic-impregnated or silver-impregnated shunts. The study showed a lower rate of infection in the antibiotic-impregnated group accordingly. ¹⁶ In fact, a retrospective study had noted that infections were common in the first month after placement. ¹⁷ As such in our patient various considerations should have been held due to his co-morbidities such as alcoholism, pulmonary coccidiomycosis, and so on. Patients with fungal infections resulting in communicating hydrocephalus should be considered for not only postoperative antibiotics but also antibiotic-impregnated catheters. Such antibiotics should not only cover gram positives but also gram negatives as well especially in patients that have co-morbidities since patients with fungal disease, particularly coccidiomycosis tend to be more immunocompromised, given that 60% of all individuals who are infected with coccidioides tend to be either mildly symptomatic or asymptomatic. ¹⁸

Even though using antibiotics and prolonged antibiotic prophylaxis might create more resistant microorganisms, this case should serve as an exception to the rule. Recommendations should be made to patients who have various co-morbidities to have perioperative prophylaxis with broader spectrum antibiotics rather than just cefazolin, vancomycin, or clindamycin, in order to cover gram negatives. ¹³ Antibiotics that should be considered are third- or fourth-generation cephalosporins due to their activity against Enterobacterales and their ability to penetrate the central nervous system (CNS). Various third-generation cephalosporins, such as ceftriaxone and ceftazidime, or a fourth-generation such as cefepime should have been initially considered prophylactically due to their broad spectrum of activity against Proteus mirabilis and other gram negatives.^19-21

Frequent monitoring of the patient’s mentation after shunt placement is prudent to ensure no post-surgical infections, and adequate CSF drainage through the shunt. If said shunts are draining an adequate amount of CSF and the patient mentation has not improved or has worsened, then further imaging may be warranted. In our case, MRI findings had shown that the patient had an infected shunt, and prompt removal of the VP shunt and EVD placement was done with administration of systemic antibiotics. Prior studies have shown this method to have a high success rate. ²²

Conclusion

Overall, it should also be noted that although gram-positive organisms are the most common cause of shunt-related infections, this does not mean that other organisms be neglected. This is especially true in patients that have a history of various co-morbidities, especially fungal infection, and as such, broader spectrum antibiotics should be strongly considered in a perioperative setting. Post-operative broad-spectrum antibiotics for 24 hours or an antibiotic-impregnated catheter should also be considered in patients with a history of co-morbidities, given that infections tend to occur most often during the first month of stent placement. ¹⁷ Patient’s mentation should also be consistently monitored to not only ensure that the stent is draining accordingly but also ensure that no other complications arise. However, if worsening mentation were to occur, a re-evaluation should be done with imaging such as CT scan with further MRI imaging if deemed necessary. Lumbar punctures should be done with gram stain and culture for more appropriate antibiotic coverage. Hopefully, such changes in management provide better care to patients and help prevent shunt infections and complications in the future.